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  1. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  2. FACTORS ADVERSELY AFFECTING AMPHIBIAN POPULATIONS IN THE US

    EPA Science Inventory

    Factors known or suspected to be adversely affecting native amphibian populations in the US were identified using information from species accounts written in a standardized format by multiple authors in a forthcoming book. Specific adverse factors were identified for 53 (58%) of...

  3. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  4. Renal function trajectory over time and adverse clinical outcomes.

    PubMed

    Sohel, Badrul Munir; Rumana, Nahid; Ohsawa, Masaki; Turin, Tanvir Chowdhury; Kelly, Martina Ann; Al Mamun, Mohammad

    2016-06-01

    The growing burden of chronic kidney disease (CKD), with its associated morbidity and mortality, is recognized as a major public health problem globally and causing substantial load on health care systems. The current framework for the definition and staging of CKD, based on eGFR levels or presence of kidney damage, is useful for clinical classification of patients, but identifies a huge number of people as having CKD which is too many to target for intervention. The ability to identify a subset of patients, at high risk for adverse outcomes, would be useful to inform clinical management. The current staging system applies static definitions of kidney function that fail to capture the dynamic nature of the kidney disease over time. Now-a-days, it is possible to capture multiple measurements of different laboratory test results for an individual including eGFR values. A new possibility for identifying individuals at higher risk of adverse outcomes is being explored through assessment and consideration of the rate of change in kidney function over time, and this approach will be feasible in the current context of digitalization of health record keeping system. On the basis of the existing evidence, this paper summarizes important findings that support the concept of dynamic changes in kidney function over time, and discusses how the magnitude of these changes affect the future adverse outcomes of kidney disease, particularly the End Stage Renal Disease (ESRD), CVD and mortality. PMID:26728745

  5. [Reporting adverse reactions and events in randomised clinical trials].

    PubMed

    Hemmingsen, Bianca; Støy, Lina; Wetterslev, Jørn; Tarnow, Lise; Friis, Karin Bach; Christensen, Louise Lundby; Sales, Nader; Gluud, Christian

    2010-08-30

    "Good clinical practice" (GCP) is an international guideline on how to conduct clinical trials on medical products involving human participants. Danish statute follows the EU trial directive (2001/20/EF) including the GCP guidelines. This article summarises the practical implementation of reporting adverse events and adverse reactions to the Danish Medicines Agency and the regional ethics committee based on the protocol of the ongoing Copenhagen Insulin and Metformin Therapy (CIMT) trial. PMID:20825743

  6. The duty to disclose adverse clinical trial results.

    PubMed

    Liao, S Matthew; Sheehan, Mark; Clarke, Steve

    2009-08-01

    Participants in some clinical trials are at risk of being harmed and sometimes are seriously harmed as a result of not being provided with available, relevant risk information. We argue that this situation is unacceptable and that there is a moral duty to disclose all adverse clinical trial results to participants in clinical trials. This duty is grounded in the human right not to be placed at risk of harm without informed consent. We consider objections to disclosure grounded in considerations of commercial interest, and we argue that these concerns are insufficient to override the moral duty to disclose adverse clinical trial results. However, we also develop a proposal that enables commercial interests to be protected, while promoting the duty to disclose adverse clinical trial results. PMID:19998154

  7. Adversity before conception will affect adult progeny in rats.

    PubMed

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:19209986

  8. The synthetic progestin megestrol acetate adversely affects zebrafish reproduction.

    PubMed

    Han, Jian; Wang, Qiangwei; Wang, Xianfeng; Li, Yonggang; Wen, Sheng; Liu, Shan; Ying, Guangguo; Guo, Yongyong; Zhou, Bingsheng

    2014-05-01

    Synthetic progestins contaminate the aquatic ecosystem, and may cause adverse health effects on aquatic organisms. Megestrol acetate (MTA) is present in the aquatic environment, but its possible effects on fish reproduction are unknown. In the present study, we investigated the endocrine disruption and impact of MTA on fish reproduction. After a pre-exposure period of 14 days, reproductively mature zebrafish (Danio rerio) (F0) were exposed to MTA at environmental concentrations (33, 100, 333, and 666 ng/L) for 21 days. Egg production was decreased in F0 fish exposed to MTA, with a significant decrease at 666 ng/L. The exposure significantly decreased the circulating concentrations of estradiol (E2) and testosterone (T) in female fish or 11-keto testosterone (11-KT) in male fish. MTA exposure significantly downregulated the transcription of certain genes along the hypothalamic-pituitary-gonadal (HPG) axis. MTA did not affect early embryonic development or hatching success in the F1 generation. The present study showed that MTA is a potent endocrine disruptor in fish, and short-term exposure to MTA could significantly affect reproduction in fish and negatively impact the fish population. PMID:24647012

  9. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  10. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  11. The automation of clinical trial serious adverse event reporting workflow

    PubMed Central

    London, Jack W; Smalley, Karl J; Conner, Kyle; Smith, J Bruce

    2011-01-01

    Background The reporting of serious adverse events (SAEs) is a requirement when conducting a clinical trial involving human subjects, necessary for the protection of the participants. The reporting process is a multi-step procedure, involving a number of individuals from initiation to final review, and must be completed in a timely fashion. Purpose The purpose of this project was to automate the adverse event reporting process, replacing paper-based processes with computer-based processes, so that personnel effort and time required for serious adverse event reporting was reduced, and the monitoring of reporting performance and adverse event characteristics was facilitated. Methods Use case analysis was employed to understand the reporting workflow and generate software requirements. The automation of the workflow was then implemented, employing computer databases, web-based forms, electronic signatures, and email communication. Results In the initial year (2007) of full deployment, 588 SAE reports were processed by the automated system, eSAEy™. The median time from initiation to Principal Investigator electronic signature was less than 2 days (mean 7 ± 0.7 days). This was a significant reduction from the prior paper-based system, which had a median time for signature of 24 days (mean of 45 ± 5.7 days). With eSAEy™, reports on adverse event characteristics (type, grade, etc.) were easily obtained and had consistent values based on standard terminologies. Limitation The automated system described was designed specifically for the work flow at Thomas Jefferson University. While the methodology for system design, and the system requirements derived from common clinical trials adverse reporting procedures are applicable in general, specific work flow details may not relevant at other institutions. Conclusion The system facilitated analysis of individual investigator reporting performance, as well as the aggregation and analysis of the nature of reported adverse

  12. Adverse effects of acupuncture. Which are clinically significant?

    PubMed Central

    Chung, Ainee; Bui, Luke; Mills, Edward

    2003-01-01

    OBJECTIVE: To review potentially serious adverse events associated with acupuncture. QUALITY OF EVIDENCE: Studies in the medical literature primarily provide level II evidence from retrospective reviews, case reports, and prospective surveys of practitioners. MAIN MESSAGE: Both the general public and physicians are becoming more interested in the ancient Chinese medical practice of acupuncture. This paper discusses the basic philosophy of acupuncture and describes adverse events that might be associated with acupuncture treatment. Some events, such as nausea and syncope, can be mild and transient, but rare events, such as septicemia and hepatitis C infection, can be fatal. As the role of acupuncture in today's multidisciplinary clinics increases, the complications of acupuncture, although infrequent, cannot be overlooked. CONCLUSION: Responsible clinicians practising acupuncture and seeing patients who use acupuncture should be aware of the adverse events associated with it. PMID:12943357

  13. [ Preventing adverse drug events using clinical decision support systems].

    PubMed

    Salili, Ali Reza; Hammann, Felix; Taegtmeyer, Anne B

    2015-12-01

    Adverse drug events pose a great risk to patients, are an everyday clinical problem and can have potential/ega/ consequences. Computerized physician order entry or computerized provider order entry (CPOE} in combination with clinical decision support systems {CDSS) are popular and aim to reduce prescribing errors as well as identifying potentially harmful drug drug interactions. The quantifiable benejit these systems bring to patients, has however, yet to be definitively proven. This article focusses on the current standpoint of CPOE-/CDSS, their risks and benefits, the potential for improvement and their perspectives for the future. PMID:26654813

  14. Obesity Adversely Affects Survival in Pancreatic Cancer Patients

    PubMed Central

    McWilliams, Robert R.; Matsumoto, Martha E.; Burch, Patrick A.; Kim, George P.; Halfdanarson, Thorvardur R.; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R.

    2010-01-01

    Purpose Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. We assessed the association of BMI with survival in a sample of pancreatic cancer patients and utilized epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. Methods A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1,861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self reported diabetes and fasting blood glucose in the survival model. Results BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma [hazard ratio 1.019 for each increased unit of BMI (kg/m2), p < 0.001] after adjustment for age, stage, and sex. In analysis by National Institutes of Health BMI category, BMI of 30–34.99 kg/m2 (HR 1.14, 95% confidence interval 0.98–1.33), 35–39.99 kg/m2 (HR 1.32, 95% CI 1.08–1.62), and ≥40 (HR 1.60, 95% CI 1.26–2.04) were associated with decreased survival compared to normal BMI of 18,5–24.99 kg/m2 (overall trend test p<0.001). Fasting blood glucose and diabetes did not affect the results. Conclusions Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. PMID:20665496

  15. Adverse drug reactions and safety considerations of NSAIDs: clinical analysis.

    PubMed

    Bahadur, Shiv; Keshri, Lav; Pathak, Kamla

    2011-11-01

    NSAIDs are the most frequently used drugs for treatment, in Europe and the United States, accounting for approximately 5% of all prescriptions. Moreover, the use of NSAIDs is increasing because these constitute the first-line drug therapy for a wide range of rheumatic conditions. This increase is in part the result of the increasing population of elderly patients, who constitute the group of patients with greatest demand for these agents. There are many types of NSAIDs that vary in potency, action and potential side effects. Thus various efforts have been made to determine the safety considerations including adverse drug effects, duration of drug therapy, drug interactions, precautions and other drugs applied to reduce side effects. Researchers have introduced some novel techniques to diagnose NSAIDs related adverse effects on the gastrointestinal mucosa. The researchers dealing with the development of drug delivery system for these drugs should aim at designing a therapeutically efficacious dosage form with reduced side/adverse effects. Thus an effort has been made in this review to deal with the safety parameters of various NSAIDs with a special emphasis on preclinical and clinical safety analysis and various attempts to minimize the side effects by structural modification or by drug delivery system. PMID:22424538

  16. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  17. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  18. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  19. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  20. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  1. Missing Out: Excessive Absenteeism Adversely Affects Elementary Reading Scores

    ERIC Educational Resources Information Center

    Hockert, Christine; Harrington, Sonja; Vaughn, Debra; Kelly, Kirk; Gooden, John

    2005-01-01

    This study was designed to answer the question "Does excessive absenteeism affect student academic achievement?" During the 2002-2003 academic year, 188 students attending grades 3 through 5 at an urban Tennessee elementary school with a high poverty level participated in the study. Demographic data were gathered to provide descriptive statistics…

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

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    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. PMID:26986231

  3. Root-Zone Glyphosate Exposure Adversely Affects Two Ditch Species

    PubMed Central

    Saunders, Lyndsay E.; Koontz, Melissa B.; Pezeshki, Reza

    2013-01-01

    Glyphosate, one of the most applied herbicides globally, has been extensively studied for its effects on non-target organisms. In the field, following precipitation, glyphosate runs off into agricultural ditches where it infiltrates into the soil and thus may encounter the roots of vegetation. These edge-of-field ditches share many characteristics with wetlands, including the ability to reduce loads of anthropogenic chemicals through uptake, transformation, and retention. Different species within the ditches may have a differential sensitivity to exposure of the root zone to glyphosate, contributing to patterns of abundance of ruderal species. The present laboratory experiment investigated whether two species commonly found in agricultural ditches in southcentral United States were affected by root zone glyphosate in a dose-dependent manner, with the objective of identifying a sublethal concentration threshold. The root zone of individuals of Polygonum hydropiperoides and Panicum hemitomon were exposed to four concentrations of glyphosate. Leaf chlorophyll content was measured, and the ratio of aboveground biomass to belowground biomass and survival were quantified. The findings from this study showed that root zone glyphosate exposure negatively affected both species including dose-dependent reductions in chlorophyll content. P. hydropiperdoides showed the greatest negative response, with decreased belowground biomass allocation and total mortality at the highest concentrations tested. PMID:24833234

  4. Urban sprawl and you: how sprawl adversely affects worker health.

    PubMed

    Pohanka, Mary; Fitzgerald, Sheila

    2004-06-01

    Urban sprawl, once thought of as just an environmental issue, is currently gaining momentum as an emerging public health issue worthy of research and political attention. Characteristics seen in sprawling communities include increasing traffic volumes; inadequate public transportation; pedestrian unfriendly streets; and the division of businesses, shops, and homes. These characteristics can affect health in many ways. Greater air pollution contributes to higher asthma and other lung disorder rates. An increased dependence on the automobile encourages a more sedentary lifestyle and can potentially contribute to obesity. The increased danger and stress of long commutes can lead to more accidents, anxiety, and social isolation. Occupational health nurses can become involved by promoting physical activity in the workplace, creating programs for injury prevention and stress management, becoming involved in political smart growth measures, and educating and encouraging colleagues to become active in addressing this issue. PMID:15219110

  5. Serious adverse event reporting in investigator-initiated clinical trials.

    PubMed

    Wallace, Sophie; Myles, Paul S; Zeps, Nikolajs; Zalcberg, John R

    2016-04-01

    Reporting adverse events (AEs) and serious AEs (SAEs) are practical steps to ensure safety for volunteers and patients in medical research involving medications, treatments and devices. However, the burden and cost of reporting should be proportionate with the public health benefit of this information. Unfortunately, in Australia there is clear evidence of ever-increasing requirements from sponsors and ethics committees to report AEs and SAEs unnecessarily, leading to a decrease in the uptake of research, particularly less well funded investigator-initiated trials. We believe that individual AE reports to ethics committees serve no useful purpose, because in most cases the study group identity (drug exposure) is not known in studies with blinded treatment arms and their value is limited. Pragmatic, investigator-initiated Phase IV clinical trials of post-marketed drugs or devices are needed to understand their role in everyday clinical practice. In this setting, the workload and costs of systematic, complete reporting of all AEs and SAEs (independent of whether these are treatment-related) is wasteful, and mostly unnecessary. A trial data safety and monitoring committee is in the unique position of being able to review safety information according to the blinded treatment arms of the study. This enables safety data to be analysed appropriately and a summary report provided to the trial steering committee, principal investigators and the relevant ethics committees in a meaningful way. Defined trial endpoints do not need to be reported as safety events (because they are being properly monitored and analysed). PMID:27031396

  6. Relationship between childhood adversity and clinical and cognitive features in schizophrenia.

    PubMed

    McCabe, Kathryn L; Maloney, Elizabeth A; Stain, Helen J; Loughland, Carmel M; Carr, Vaughan J

    2012-05-01

    Childhood adversity is associated with elevated risk for a wide range of adult psychiatric disorders, and has significant and sustained negative effects on adult behavioural and social functioning. Elevated rates of childhood adversity have been reported for people with a diagnosis of schizophrenia. The aim of the present study was to assess rates of retrospectively reported childhood adversity among adults with schizophrenia and to examine the relationship between childhood adversity and clinical and cognitive features. Data were available for 408 schizophrenia participants and 267 healthy control participants recruited through the Australian Schizophrenia Research Bank (ASRB). History of childhood adversity was obtained using the Childhood Adversity Questionnaire (CAQ). A five-factor solution was identified from the CAQ. Schizophrenia participants reported experiencing more childhood adversities than controls. In both groups, those reporting childhood adversity were more likely to be female and older. Among participants with schizophrenia, positive symptom severity and fewer years of education were associated with childhood adversity. Lower IQ scores and personality traits were associated with reporting a greater number of childhood adversities and with adversity sub-types of abusive, neglectful and dysfunctional parenting. The rate of childhood adversity reported in this sample was high which suggests greater exposure to adverse childhood events among participants with schizophrenia in comparison with healthy controls. We identified unique groups amongst CAQ items that provided a salient framework from which to investigate the connection between childhood adversity and clinical and cognitive features. PMID:22329951

  7. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

  8. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  9. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  10. [Adverse reaction induced by licorice preparations: clinical analysis of 93 cases].

    PubMed

    Mao, Min; Li, Wei; Wang, Wei; Wang, Shu-Xia; Lu, Jin; Chang, Zhang-Fu

    2013-11-01

    Licorice is a traditional Chinese medicine commonly used in clinic. The products,what contain licorice or licorice extract, has early been involved in the field of cosmetics except for the field of pharmaceuticals and food. Consequently, the reporting on adverse reactions induced by licorice preparations are more frequent. Based on the clinical data of licorice preparations adverse reactions, we described the characteristics of the licorice-related adverse reactions, and proposed specific measures to reduce the incidence of adverse reactions, provided a reference for the rational use of licorice preparations. PMID:24494570

  11. 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

  12. 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. PMID:27086207

  13. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40...-78.40 What responsibilities do Federal agencies have when an undertaking adversely affects a...

  14. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  15. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  16. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... that are not likely to adversely affect listed species or critical habitat. 402.45 Section 402.45... habitat. (a) Consultation obligations for FIFRA actions that are not likely to adversely affect listed species or critical habitat when alternative consultation agreement is in effect. If EPA and the...

  17. Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal Candidiasis

    PubMed Central

    Bliss, Joseph M.; Wong, Angela Y.; Bhak, Grace; Laforce-Nesbitt, Sonia S.; Taylor, Sarah; Tan, Sylvia; Stoll, Barbara J.; Higgins, Rosemary D.; Shankaran, Seetha; Benjamin, Daniel K.

    2012-01-01

    Objective To determine if premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains. Study design Clinical isolates were studied from 2 populations; premature infants colonized with Candida (commensal, n=27), and those with invasive candidiasis (n=81). Individual isolates of C. albicans and C. parapsilosis were tested for virulence in each of 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if they measured more than 1 SD above the mean for the commensal isolates in at least 1 assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics. Results 61% of invasive isolates of C. albicans and 42% of invasive isolates of C. parapsilosis had enhanced virulence. All C. albicans cerebrospinal fluid (CSF) isolates (n=6) and 90% of urine isolates (n=10) had enhanced virulence, compared with 48% of blood isolates (n=40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine. Conclusions Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes. PMID:22504098

  18. Drug adverse events and drop-out risk: a clinical case.

    PubMed

    Scoyni, R M; Aiello, L; Trani, I; Felli, B; Masin, A M R; Camponi, V; Dignazio, L; Cortese, M; Pacitti, M T; Carratelli, D; Morocutti, C

    2007-01-01

    We report a brief discussion on a clinical case of a female patient, 85 years old, affected by severe cognitive impairment and chronic obstructive pulmonary disease (COPD). The patient was not taking drugs at home (apart from promazine: 10 drops when necessary to control her behavioral diseases). A previous neuropsychological evaluation had shown a severe cognitive impairment MMSE=16/30; ADL=3/6; IADL=0/8) due to multiple brain ischemic areas (confirmed in 2003 by MRI neuroimaging). When the patient was admitted to our center she was able to perform some basic activities of daily living such as eating and walking and was not too confused. She was included in cognitive rehabilitation groups. Since she showed signs of Parkinsonism, a therapy based on omeprazol 20mg, acetylsalicylic acid, donepezil 10mg, pramipexol 0.18 mg, nimodipine 10 drops, levodopa+carbidopa 100/25mg was started. A few days later she became sleepy during daytime and, once, she lost her balance and fell. She was not self-sufficient any more. At first this was attributed to a lung infection that the patient had, but her state continue after the infection was completely cured with appropriate antibiotics therapy. At that point an adverse drug reaction was suspected and therapy with pramipexol 0.18 mg was interrupted. In a few days the patient regained her previous level of consciousness and self-sufficiency. We consider this a typical case of complex management in a patient with dementia and comorbidity in which adverse drug reactions can play an important role in lowering the level of cognitive functions. In this case the relationship with the family of the patient was made difficult by the attitude of the patient's daughter who decided, after the onset of the adverse drug reaction, to interrupt her mother's stay in our center even at risk of the worst consequences. PMID:17317475

  19. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  20. Increasing the Number of Adverse Drug Reactions Reporting: the Role of Clinical Pharmacy Residents

    PubMed Central

    Baniasadi, Shadi; Habibi, Maryam; Haghgoo, Roodabeh; Karimi Gamishan, Masoumeh; Dabaghzadeh, Fatemeh; Farasatinasab, Maryam; Farsaei, Shadi; Gharekhani, Afshin; Kafi, Hamidreza; Karimzadeh, Iman; Kharazmkia, Ali; Najmeddin, Farhad; Nikvarz, Naemeh; Oghazian, Mohammad Bagher; Rezaee, Haleh; Sadeghi, Kourosh; Tafazzoli, Ali; Shahsavari, Nahid; Fahimi, Fanak

    2014-01-01

    Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents' involvement in the ADR reporting program could improve the ADR reporting system. PMID:24734083

  1. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  2. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  3. The role of the clinical pharmacologist in the management of adverse drug reactions.

    PubMed

    Moore, N

    2001-01-01

    The classical definition of clinical pharmacology is the study or the knowledge of the effects of drugs in humans. The activities of a clinical pharmacologist can vary from country to country, usually ranging from involvement in clinical trials, especially fundamental pharmacodynamic studies, to studies of pharmacokinetics and drug metabolism, to pharmacogenetics. Most clinical pharmacologists outside industry are in hospitals or university hospitals and research centres. In addition to research, this implies teaching of clinical pharmacology, and interacting with other medical staff: in the field of research, giving advice on clinical trials methodology and often managing a therapeutic drug monitoring centre. Some clinical pharmacologists have clinical departments with beds or consulting offices. Can there be another role for the clinical pharmacologist that would increase his or her usefulness for the medical community? Adverse drug reactions (ADRs) are remarkably complex events, related to drug effects, patient characteristics (background diseases, genetics), and drug/disease interactions. Evaluation of ADRs requires understanding of drug mechanisms and interactions, and of disease diagnostics, especially in the discussion of alternative diagnoses. This implies expertise as a pharmacologist and a clinician. In addition, because not all adverse reactions or interactions are in the Summary of Product Characteristics, and because problems arise long before they report in the literature, it is necessary for the clinical pharmacologist to have knowledge of ongoing regulatory processes, in addition to having access to the published literature. Helping clinicians cope with individual patient problems will also improve the clinical pharmacologist's integration into the healthcare process. PMID:11219484

  4. Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory.

    PubMed

    Seyer, Benjamin; Pham, Vi; Albiston, Anthony L; Chai, Siew Yeen

    2016-08-15

    Indwelling cannulas are often used to deliver pharmacological agents into the lateral ventricles of the brain to study their effects on memory and learning, yet little is known about the possible adverse effects of the cannulation itself. In this study, the effect of implanting an indwelling cannula into the right lateral ventricle was examined with respect to cognitive function and tissue damage in rats. Specifically, the cannula passed through sections of the primary motor (M1) and somatosensory hind limb (S1HL) cortices. One week following implantation, rats were impaired on the rotarod task, implying a deficit in fine motor control, likely caused by the passage of the cannula through the aforementioned cortical regions. Importantly, neither spatial working nor recognition memory was adversely affected. Histological examination showed immune cell activation only in the area immediately surrounding the cannulation site and not spreading to other brain regions. Both GFAP and CD-11b mRNA expression was elevated in the area immediately surrounding the cannulation site, but not in the contralateral hemisphere or the hippocampus. Neither of the inflammatory cytokines, TNF-α or IL-6, were upregulated in any region. These results show that cannulation into the lateral ventricle does not impair cognition and indicates that nootropic agents delivered via this method are enhancing normal memory rather than rescuing deficits caused by the surgery procedure. PMID:27345383

  5. Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

    PubMed

    Lambert, Jennifer; Lamothe, Jeremy M; Zernicke, Ronald F; Auer, Roland N; Reimer, Raylene A

    2005-02-01

    The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass. PMID:15585686

  6. Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

    PubMed Central

    Awadzi, Kwablah

    2003-01-01

    Ivermectin (Mectizan®) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan® reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed. PMID:14975063

  7. Embedding surveillance into clinical care to detect serious adverse events in pregnancy.

    PubMed

    Seale, Anna C; Barsosio, Hellen C; Koech, Angela C; Berkley, James A

    2015-11-25

    Severe maternal complications in pregnancy in sub-Saharan Africa contribute to high maternal mortality and morbidity. Incidence data on severe maternal complications, life-threatening conditions, maternal deaths and birth outcomes are essential for clinical audit and to inform trial design of the types and frequency of expected severe adverse events (SAEs). However, such data are very limited, especially in sub-Saharan Africa. We set up standardized, systematic clinical surveillance embedded into routine clinical care in a rural county hospital in Kenya. Pregnant women and newborns are systematically assessed and investigated. Data are reported using a standardized Maternal Admission Record that forms both the hospital's clinical record and the data collection tool. Integrating clinical surveillance with routine clinical care is feasible and should be expanded in sub-Saharan Africa, both for improving clinical practice and as a basis for intervention studies to reduce maternal and newborn mortality and morbidity where rates are highest. PMID:26254977

  8. Embedding surveillance into clinical care to detect serious adverse events in pregnancy

    PubMed Central

    Seale, Anna C; Barsosio, Helen C; Koech, Angela; Berkley, James A

    2016-01-01

    Severe maternal complications in pregnancy in sub-Saharan Africa contribute to high maternal mortality and morbidity. Incidence data on severe maternal complications, life-threatening conditions, maternal deaths and birth outcomes are essential for clinical audit and to inform trial design of the types and frequency of expected severe adverse events (SAEs). However, such data are very limited, especially in sub-Saharan Africa. We set up standardized, systematic clinical surveillance embedded into routine clinical care in a rural county hospital in Kenya. Pregnant women and newborns are systematically assessed and investigated. Data are reported using a standardized Maternal Admission Record that forms both the hospital’s clinical record and the data collection tool. Integrating clinical surveillance with routine clinical care is feasible and should be expanded in sub-Saharan Africa, both for improving clinical practice and as a basis for intervention studies to reduce maternal and newborn mortality and morbidity where rates are highest. PMID:26254977

  9. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  10. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  11. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  12. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  13. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  14. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  15. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  16. The Impact of Childhood Adversity on the Clinical Features of Schizophrenia.

    PubMed

    Rajkumar, Ravi Philip

    2015-01-01

    Introduction. Recent research has drawn attention to the link between childhood maltreatment and schizophrenia. Child abuse and neglect may have an impact on symptoms and physical health in these patients. This association has not been studied to date in India. Materials and Methods. Clinically stable patients with schizophrenia (n = 62) were assessed for childhood adversity using the Childhood Trauma Questionnaire. The association of specific forms of adversity with symptomatology and associated variables was examined. Results. Emotional abuse was reported by 56.5% patients and physical abuse by 33.9%; scores for childhood neglect were also high. Persecutory delusions were linked to physical abuse, while anxiety was linked to emotional neglect and depression to emotional abuse and childhood neglect. Physical abuse was linked to elevated systolic blood pressure, while emotional abuse and neglect in women were linked to being overweight. Conclusions. Childhood adversity is common in schizophrenia and appears to be associated with a specific symptom profile. Certain components of the metabolic syndrome also appear to be related to childhood adversity. These results are subject to certain limitations as they are derived from remitted patients, and no control group was used for measures of childhood adversity. PMID:26345291

  17. The Impact of Childhood Adversity on the Clinical Features of Schizophrenia

    PubMed Central

    Rajkumar, Ravi Philip

    2015-01-01

    Introduction. Recent research has drawn attention to the link between childhood maltreatment and schizophrenia. Child abuse and neglect may have an impact on symptoms and physical health in these patients. This association has not been studied to date in India. Materials and Methods. Clinically stable patients with schizophrenia (n = 62) were assessed for childhood adversity using the Childhood Trauma Questionnaire. The association of specific forms of adversity with symptomatology and associated variables was examined. Results. Emotional abuse was reported by 56.5% patients and physical abuse by 33.9%; scores for childhood neglect were also high. Persecutory delusions were linked to physical abuse, while anxiety was linked to emotional neglect and depression to emotional abuse and childhood neglect. Physical abuse was linked to elevated systolic blood pressure, while emotional abuse and neglect in women were linked to being overweight. Conclusions. Childhood adversity is common in schizophrenia and appears to be associated with a specific symptom profile. Certain components of the metabolic syndrome also appear to be related to childhood adversity. These results are subject to certain limitations as they are derived from remitted patients, and no control group was used for measures of childhood adversity. PMID:26345291

  18. Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus)

    PubMed Central

    Tahamtani, Fernanda M.; Nordgreen, Janicke; Nordquist, Rebecca E.; Janczak, Andrew M.

    2015-01-01

    Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

  19. Extraction Of Adverse Events From Clinical Documents To Support Decision Making Using Semantic Preprocessing.

    PubMed

    Gaebel, Jan; Kolter, Till; Arlt, Felix; Denecke, Kerstin

    2015-01-01

    Clinical documentation is usually stored in unstructured format in electronic health records (EHR). Processing the information is inconvenient and time consuming and should be enhanced by computer systems. In this paper, a rule-based method is introduced that identifies adverse events documented in the EHR that occurred during treatment. For this purpose, clinical documents are transformed into a semantic structure from which adverse events are extracted. The method is evaluated in a user study with neurosurgeons. In comparison to a bag of word classification using support vector machines, our approach achieved comparably good results of 65% recall and 78% precision. In conclusion, the rule-based method generates promising results that can support physicians' decision making. Because of the structured format the data can be reused for other purposes as well. PMID:26262330

  20. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  1. Probabilities of adverse weather affecting transport in Europe: climatology and scenarios up to the 2050s

    NASA Astrophysics Data System (ADS)

    Vajda, A.; Tuomenvirta, H.; Jokinen, P.; Luomaranta, A.; Makkonen, L.; Tikanmäki, M.; Groenemeijer, P.; Saarikivi, P.; Michaelides, S.; Papadakis, M.; Tymvios, F.; Athanasatos, S.

    2012-04-01

    This paper provides the first comprehensive climatology of the adverse and extreme weather events affecting the European transport system by estimating the frequency (or probability) of phenomena for the present climate (1971-2000) and an overview of the projected changes in some of these extremes in the future climate until the 2050s. The research was carried out within the framework of the EWENT Project that addresses the European Union (EU) policies and strategies related to climate change, with a particular focus on extreme weather impacts on the EU transportation system. This project is funded by the Seventh Framework Programme (Transports, call ID FPT7-TPT-2008-RTD-1). The analyzed phenomena are wind, snow, blizzards, heavy precipitation, cold spells and heat waves. In addition, reduced visibility conditions determined by fog and dust events, small-scale phenomena affecting the transport system, such as thunderstorms, lightning, large hail and tornadoes and events damaging infrastructure of the transport system, have been considered. Frequency and probability analysis of past and present ex¬tremes were performed using observational and atmospheric reanalysis data. Future changes in the probability of severe events were assessed based on six regional climate model simulations produced in the FP6 ENSEMBLES project (http://www.ensembles-eu.org/). To facilitate the assessment of impacts and consequences of extreme phenomena on a continental level, the WP2 Deliverable introduces a regionalization of the European extreme phenomena, defining the climate zones with similarities in extreme phenomena. The projected changes as well as large natural variability in weather extremes on the transportation network will have impacts of both signs. The decline of extreme cold and snowfall over most of the continent implies a positive impact on road, rail, inland water and air transportation, e.g., by reducing snow removal. However, even with a general decreasing trend in

  2. 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. PMID:26291578

  3. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects

    PubMed Central

    Zhanel, George G; Simor, Andrew E; Vercaigne, Lavern; Mandell, Lionell

    1998-01-01

    OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references. DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected. DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar. CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost. PMID:22346545

  4. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40... (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 78-HISTORIC PRESERVATION Historic Preservation §...

  5. 25 CFR 900.244 - Will an Indian tribe or tribal organization's retrocession adversely affect funding available for...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Will an Indian tribe or tribal organization's retrocession adversely affect funding available for the retroceded program? 900.244 Section 900.244 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR, AND INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES CONTRACTS UNDER THE...

  6. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  7. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  8. 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

  9. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    PubMed

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell. PMID:25382136

  10. Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention.

    PubMed

    Fujiwara, Takayuki; Yoshida, Masashi; Akashi, Naoyuki; Yamada, Hodaka; Tsukui, Takunori; Nakamura, Tomohiro; Sakakura, Kenichi; Wada, Hiroshi; Arao, Kenshiro; Katayama, Takuji; Umemoto, Tomio; Funayama, Hiroshi; Sugawara, Yoshitaka; Mitsuhashi, Takeshi; Kakei, Masafumi; Momomura, Shin-Ichi; Ako, Junya

    2016-06-01

    Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86-0.99, p = 0.04; 0.90, 0.81-0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI. PMID:25921916

  11. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  12. Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

    PubMed

    Garbino, Jorge; Markham, Lydia; Matulionyte, Raimonda; Rives, Vincent; Lew, Daniel

    2006-01-01

    Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy. PMID:16449001

  13. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    ERIC Educational Resources Information Center

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  14. A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies.

    PubMed

    Izzo, Angelo A; Hoon-Kim, Sung; Radhakrishnan, Rajan; Williamson, Elizabeth M

    2016-05-01

    Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887532

  15. Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines

    PubMed Central

    Warrer, Pernille; Jensen, Peter Bjødstrup; Aagaard, Lise; Jensen, Lars Juhl; Brunak, Søren; Krag, Malene Hammer; Rossing, Peter; Almdal, Thomas; Andersen, Henrik Ullits; Hansen, Ebba Holme

    2015-01-01

    Objective: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: “Combinations of oral blood-glucose lowering medicines” (A10BD), “dipeptidyl peptidase-4 (DDP-4) inhibitors” (A10BH), and “other blood glucose lowering medicines” (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment. Methods: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status. Findings: A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with “other blood glucose lowering medications,” the remaining 2 (13%) with “DDP-4 inhibitors.” Conclusion: Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs. PMID:25984543

  16. 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

  17. Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes

    PubMed Central

    Jia, Xiaoyu; Heller, Glenn; Barz, Allison; Sit, Laura; Fruscione, Michael; Appawu, Mark; Iasonos, Alexia; Atkinson, Thomas; Goldfarb, Shari; Culkin, Ann; Kris, Mark G.; Schrag, Deborah

    2009-01-01

    Background In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. Methods Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. Results A total of 163 patients were enrolled for an average of 12 months (range = 1–28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. Conclusions Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are

  18. 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. PMID:26141794

  19. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    PubMed Central

    Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

    2013-01-01

    OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

  20. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources..., pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or...

  1. Ketotifen treatment of adverse reactions to foods: clinical and immunological effects.

    PubMed

    Ciprandi, G; Scordamaglia, A; Ruffoni, S; Pizzorno, G; Canonica, G W

    1986-01-01

    Fifteen patients with cutaneous signs and symptoms caused by adverse reactions to foods were treated in an open trial with ketotifen for 4 to 6 weeks. Seven subjects were allergic and 8 had food intolerance. Each patient was treated with a single dose of ketotifen daily: 2 mg half an hour before going to sleep. Clinical improvement was achieved in 6 out of 7 allergic patients and in 6 out of 8 patients with food intolerance. Since several drugs have been demonstrated to have an influence on immune response, the in vitro effects of ketotifen on some immunological parameters were also studied. Ketotifen showed a significant inhibitory effect on autologous mixed lymphocyte reaction responsiveness. PMID:2949941

  2. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    ERIC Educational Resources Information Center

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  3. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  4. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-01

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders. PMID:27449360

  5. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  6. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

    PubMed Central

    Chin, Calvin W.L.; Messika-Zeitoun, David; Shah, Anoop S.V.; Lefevre, Guillaume; Bailleul, Sophie; Yeung, Emily N.W.; Koo, Maria; Mirsadraee, Saeed; Mathieu, Tiffany; Semple, Scott I.; Mills, Nicholas L.; Vahanian, Alec; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement. PMID:26491110

  7. Water pollution by Cu and Pb can adversely affect mallard embryonic development.

    PubMed

    Kertész, Virág; Bakonyi, Gábor; Farkas, Beáta

    2006-09-01

    The effects of heavy metal pollutants on aquatic birds have been widely studied in ecotoxicological investigations; however, the predominant focus has been on the postnatal period of life. Limited information on the adverse effects of metals to bird eggs is available. The possible toxic effects of lead and copper were studied in mallard eggs. After the accidental severe heavy metal pollution of the Tisa river (Hungary) in March 2000, these metals were detected in the highest concentration in both the water and the sediment, reaching far beyond acceptable concentrations. Pb treatment (2.9 mg/L) significantly increased the rate of mortality after a single immersion of the eggs into polluted water for 30 min. The rate of dead embryos significantly increased after the combined exposure to Cu and Pb (0.86 and 2.9 mg/L, respectively) both in the single- (once for 30 min) and in the multiple- (10s daily during first trimester of incubation) immersion groups. It was concluded that elevated metal concentrations similar to those found in the Tisa river after the tailing dam failure may cause toxic effects (mortality and teratogenicity) upon exposure of mallard eggs. PMID:16678261

  8. Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling

    PubMed Central

    Medzikovic, Lejla; Schumacher, Cees A.; Verkerk, Arie O.; van Deel, Elza D.; Wolswinkel, Rianne; van der Made, Ingeborg; Bleeker, Natascha; Cakici, Daniella; van den Hoogenhof, Maarten M. G.; Meggouh, Farid; Creemers, Esther E.; Ann Remme, Carol; Baartscheer, Antonius; de Winter, Robbert J.; de Vries, Carlie J. M.; Arkenbout, E. Karin; de Waard, Vivian

    2015-01-01

    Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes, and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure. PMID:26486271

  9. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

    PubMed

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  10. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

    PubMed Central

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

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

    SciTech Connect

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    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 following 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 prescribed

  12. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

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

    PubMed Central

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

    2016-01-01

    Background 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. Methods and Findings 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

  14. [Analysis on 315 cases of clinical adverse drug reaction/event induced by gastrodin].

    PubMed

    Zheng, Yang-yang; Dong, Zhi; Lu, Xiao-qin; Xia, Yong-peng; Zhu, Shu-bing

    2015-05-01

    With patients' general situation, medication use, occurrence time of adverse drug reaction/event (ADR/ADE), clinical manifestations and prognosis as reference items, a retrospective study was made for 315 cases with ADR/ADE induced by Gastrodin in Chongqing from January 2008 to June 2014, in order to analyze the characteristics of ADR/ADE and provide reference for rational clinical medication. The results showed that among the 315 cases with ADR/ADE, 143 cases (45.4%) were males and 172 cases (54.6%) were females, most of them (74.9%) were aged above 45; 60 cases (19.0%) with ADE were caused by off-label indications and 66 cases (21.0%) with ADE were caused by over dosage; ADR/ADE cases induced by intravenous drip mainly happened within 30 min (85.5%), ADR/ADE cases induced by oral administration mainly happened within 2 h (74.4%), and all of ADR/ ADE cases induced by intramuscular injection happened within 10 min. Totally 593 ADR/ADE cases were reported, which were mainly damages in gastrointestinal system, skin and its adnexa; And 61.9% of ADR/ADE cases were newly reported. It is suggested that medical workers shall learn about the regularity and characteristics of ADR/ADE induced by gastrodin, apply it in clinic with standards, pay close attention to changes of patients' situations and attach importance to the monitoring of ADR/ADE, so as to enhance the safety of medication. PMID:26390669

  15. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients.

    PubMed

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-02-01

    Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  16. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

    PubMed Central

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-01-01

    Abstract Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477–3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277–0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  17. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  18. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources BUREAU...: (a) Submit a plan of corrective action to MMS within 30 days of the discovery of the adverse...

  19. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  20. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... corrective action to BOEM within 30 days of the discovery of the adverse effect. (b) Take remedial action...

  1. Diabetes distress may adversely affect the eating styles of women with type 1 diabetes

    PubMed Central

    Quinn, Laurie; Hacker, Eileen; Park, Hanjong; Kujath, Amber S.

    2015-01-01

    The aim of this study was to determine the relationships among diabetes distress, fear of hypoglycemia, and eating styles in women with type 1 diabetes (T1DM). Fifteen women (mean age 37 ± 13.5 years) with T1DM completed surveys measuring diabetes distress, fear of hypoglycemia (FOH), and eating style. Height, weight, and A1C were obtained, and open-ended comments regarding hypoglycemic concerns and experiences were recorded. Diabetes distress was positively associated with A1C (r = .655, p = .008). High levels of external (73 %), emotional (47 %), and restrained (53 %) eating styles were reported. Emotional and external eating styles were positively associated with diabetes distress (r = .575 and r = .622; p <.05). Those with poorer glycemic control (A1C ≥ 7 %; 53 mmol/mol) had higher levels of restrained eating behavior (F = 10.69, p = .006) and greater interpersonal distress (F = 5.916, p = .03) than those with better glycemic control (A1C < 7 %; 53 mmol/mol). A nonlinear relationship was identified between interpersonal distress and FOH (behavior subscale, p = .0383) indicating that fewer behavioral approaches were employed to avoid hypoglycemia at higher distress levels. The women in this sample were emotionally burdened by their disease. Distress was associated with eating styles linked with overeating and poor glycemic control. High levels of emotional and external eating styles may have important clinical implications for those with T1DM. PMID:24615054

  2. Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia

    PubMed Central

    Beason, David P.; Tucker, Jennica J.; Lee, Chang Soo; Edelstein, Lena; Abboud, Joseph A.; Soslowsky, Louis J.

    2014-01-01

    Background Rotator cuff tendon tears represent a major component of reported orthopaedic injuries. In addition, more than one quarter of U.S. adults either currently have high cholesterol levels or have reduced their previously high cholesterol levels through the use of pharmaceuticals. Our clinical data have already linked hypercholesterolemia to full-thickness rotator cuff tears, and experimental data from our laboratory have shown effects on native tendon properties in multiple species. The objective of this study was to evaluate healing of supraspinatus tendons in our rat rotator cuff injury model. We hypothesized that tendon healing would be inferior in rats receiving a high-cholesterol diet for 6 months compared with those receiving standard chow. Methods All animals were subjected to a unilateral supraspinatus detachment and repair surgery, with contralateral limbs serving as within-animal comparative data. Animals continued their respective diet courses, and their supraspinatus tendons were biomechanically or histologically evaluated at 2, 4, and 8 weeks postoperatively. Results Biomechanical testing revealed a significant reduction in normalized stiffness in hypercholesterolemic rats compared with controls at 4 weeks after injury, whereas histologic analyses showed no significant differences in collagen organization, cellularity, or cell shape between groups. Conclusion On the basis of our findings, hypercholesterolemia may have a detrimental biomechanical effect on tendon healing in our rat rotator cuff injury and repair model. Level of evidence Basic Science Study, Animal Model. PMID:24295837

  3. Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna.

    PubMed

    Campos, Bruno; Rivetti, Claudia; Kress, Timm; Barata, Carlos; Dircksen, Heinrich

    2016-06-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immunoreactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact. PMID:27128505

  4. Combining S-cone and luminance signals adversely affects discrimination of objects within backgrounds

    PubMed Central

    Jennings, Ben J.; Tsattalios, Konstantinos; Chakravarthi, Ramakrishna; Martinovic, Jasna

    2016-01-01

    The visual system processes objects embedded in complex scenes that vary in both luminance and colour. In such scenes, colour contributes to the segmentation of objects from backgrounds, but does it also affect perceptual organisation of object contours which are already defined by luminance signals, or are these processes unaffected by colour’s presence? We investigated if luminance and chromatic signals comparably sustain processing of objects embedded in backgrounds, by varying contrast along the luminance dimension and along the two cone-opponent colour directions. In the first experiment thresholds for object/non-object discrimination of Gaborised shapes were obtained in the presence and absence of background clutter. Contrast of the component Gabors was modulated along single colour/luminance dimensions or co-modulated along multiple dimensions simultaneously. Background clutter elevated discrimination thresholds only for combined S-(L + M) and L + M signals. The second experiment replicated and extended this finding by demonstrating that the effect was dependent on the presence of relatively high S-(L + M) contrast. These results indicate that S-(L + M) signals impair spatial vision when combined with luminance. Since S-(L + M) signals are characterised by relatively large receptive fields, this is likely to be due to an increase in the size of the integration field over which contour-defining information is summed. PMID:26856308

  5. Incorporating adverse event relatedness into dose-finding clinical trial designs.

    PubMed

    Darssan, Darsy; Thompson, Mery H; Pettitt, Anthony N

    2014-03-30

    Dose-finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose-level estimation. We incorporate adverse event relatedness into the so-called continual reassessment method. Adverse events that have 'doubtful' or 'possible' relationships to the drug are modelled using a two-parameter logistic model with an additive probability mass. Adverse events 'probably' or 'definitely' related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies. PMID:24122859

  6. Nutrient supplementation may adversely affect maternal oral health--a randomised controlled trial in rural Malawi.

    PubMed

    Harjunmaa, Ulla; Järnstedt, Jorma; Dewey, Kathryn G; Ashorn, Ulla; Maleta, Kenneth; Vosti, Stephen A; Ashorn, Per

    2016-01-01

    Nutritional supplementation during pregnancy is increasingly recommended especially in low-resource settings, but its oral health impacts have not been studied. Our aim was to examine whether supplementation with multiple micronutrients (MMN) or small-quantity lipid-based nutrient supplements affects dental caries development or periodontal health in a rural Malawian population. The study was embedded in a controlled iLiNS-DYAD trial that enrolled 1391 pregnant women <20 gestation weeks. Women were provided with one daily iron-folic acid capsule (IFA), one capsule with 18 micronutrients (MMN) or one sachet of lipid-based nutrient supplements (LNS) containing protein, carbohydrates, essential fatty acids and 21 micronutrients. Oral examination of 1024 participants was conducted and panoramic X-ray taken within 6 weeks after delivery. The supplement groups were similar at baseline in average socio-economic, nutritional and health status. At the end of the intervention, the prevalence of caries was 56.7%, 69.1% and 63.3% (P = 0.004), and periodontitis 34.9%, 29.8% and 31.2% (P = 0.338) in the IFA, MMN and LNS groups, respectively. Compared with the IFA group, women in the MMN group had 0.60 (0.18-1.02) and in the LNS group 0.59 (0.17-1.01) higher mean number of caries lesions. In the absence of baseline oral health data, firm conclusions on causality cannot be drawn. However, although not confirmatory, the findings are consistent with a possibility that provision of MMN or LNS may have increased the caries incidence in this target population. Because of the potential public health impacts, further research on the association between gestational nutrient interventions and oral health in low-income settings is needed. PMID:26194850

  7. Obesity/hyperleptinemic phenotype adversely affects hippocampal plasticity: effects of dietary restriction.

    PubMed

    Grillo, Claudia A; Piroli, Gerardo G; Evans, Ashlie N; Macht, Victoria A; Wilson, Steven P; Scott, Karen A; Sakai, Randall R; Mott, David D; Reagan, Lawrence P

    2011-08-01

    Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that obesity affects the functional integrity of the central nervous system (CNS). We recently developed a lentivirus (LV) vector that produces an insulin receptor (IR) antisense RNA sequence (IRAS) that when injected into the hypothalamus selectively decreases IR signaling in hypothalamus, resulting in increased body weight, peripheral adiposity and plasma leptin levels. To test the hypothesis that this obesity/hyperleptinemic phenotype would impair hippocampal synaptic transmission, we examined short term potentiation (STP) and long term potentiation (LTP) in the hippocampus of rats that received the LV-IRAS construct or the LV-Control construct in the hypothalamus (hypo-IRAS and hypo-Con, respectively). Stimulation of the Schaffer collaterals elicits STP that develops into LTP in the CA1 region of hypo-Con rats; conversely, hypo-IRAS rats exhibit STP that fails to develop into LTP. To more closely examine the potential role of hyperleptinemia in these electrophysiological deficits, hypo-IRAS were subjected to mild food restriction paradigms that would either: 1) prevent the development of the obesity phenotype; or 2) reverse an established obesity phenotype in hypo-IRAS rats. Both of these paradigms restored LTP in the CA1 region and reversed the decreases in the phosphorylated/total ratio of GluA1 Ser845 AMPA receptor subunit expression observed in the hippocampus of hypo-IRAS rats. Collectively, these data support the hypothesis that obesity impairs hippocampal synaptic transmission and support the hypothesis that these deficits are mediated through the impairment of hippocampal leptin activity. PMID:21036186

  8. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    PubMed Central

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078

  9. Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study

    PubMed Central

    Stiell, Ian G.; Clement, Catherine M.; Aaron, Shawn D.; Rowe, Brian H.; Perry, Jeffrey J.; Brison, Robert J.; Calder, Lisa A.; Lang, Eddy; Borgundvaag, Bjug; Forster, Alan J.; Wells, George A.

    2014-01-01

    Background: To assist physicians with difficult decisions about hospital admission for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) presenting in the emergency department, we sought to identify clinical characteristics associated with serious adverse events. Methods: We conducted this prospective cohort study in 6 large Canadian academic emergency departments. Patients were assessed for standardized clinical variables and then followed for serious adverse events, defined as death, intubation, admission to a monitored unit or new visit to the emergency department requiring admission. Results: We enrolled 945 patients, of whom 354 (37.5%) were admitted to hospital. Of 74 (7.8%) patients with a subsequent serious adverse event, 36 (49%) had not been admitted after the initial emergency visit. Multivariable modelling identified 5 variables that were independently associated with adverse events: prior intubation, initial heart rate ≥ 110/minute, being too ill to do a walk test, hemoglobin < 100 g/L and urea ≥ 12 mmol/L. A preliminary risk scale incorporating these and 5 other clinical variables produced risk categories ranging from 2.2% for a score of 0 to 91.4% for a score of 10. Using a risk score of 2 or higher as a threshold for admission would capture all patients with a predicted risk of adverse events of 7.2% or higher, while only slightly increasing admission rates, from 37.5% to 43.2%. Interpretation: In Canada, many patients with COPD suffer a serious adverse event or death after being discharged home from the emergency department. We identified high-risk characteristics and developed a preliminary risk scale that, once validated, could be used to stratify the likelihood of poor outcomes and to enable rational and safe admission decisions. PMID:24549125

  10. Kinase Inhibition-Related Adverse Events Predicted from in vitro Kinome and Clinical Trial Data

    PubMed Central

    Yang, Xinan; Huang, Yong; Crowson, Matthew; Li, Jianrong; Maitland, Michael L.; Lussier, Yves A.

    2010-01-01

    Background Kinase inhibition is an increasingly popular strategy for pharmacotherapy of human diseases. Although many of these agents have been described as “targeted therapy”, they will typically inhibit multiple kinases with varying potency. Pre-clinical model testing has not predicted the numerous significant toxicities identified during clinical development. The purpose of this study was to develop a bioinformatics-based method to predict specific adverse events (AEs) in humans associated with the inhibition of particular kinase targets (KTs). Methods The AE frequencies of protein kinase inhibitors (PKIs) were curated from three sources (PubMed, Thompson Physician Desk Reference and PharmGKB), and affinities of 38 PKIs for 317 kinases, representing > 50% of the predicted human kinome, were collected from published in vitro assay results. A novel quantitative computational method was developed to predict associations between KTs and AEs that included a whole panel of 71 AEs and 20 PKIs targeting 266 distinct kinases with Kd < 10uM. The method calculated an unbiased, kinome-wide association score via linear algebra on (i) the normalized frequencies of AEs associated with 20 PKIs and (ii) the negative log-transformed dissociation constant of kinases targeted by these PKIs. Finally, a reference standard was calculated by applying Fisher’s exact test to the co-occurrence of indexed Pubmed terms (p≤0.05, and manually verified) for AE and associated kinase targets (AE-KT) pairs from standard literature search techniques. We also evaluated the enrichment of predictions between the quantitative method and the literature search by Fisher’s Exact testing. Results We identified significant associations among already empirically well established pairs of AEs (e.g. diarrhea and rash) and KTs (e.g. EGFR). The following less well recognized AE-KT pairs had similar association scores: diarrhea-(DDR1; ERBB4), rash-ERBB4, and fatigue-(CSF1R; KIT). With no filtering, the

  11. The Cultivation of Bt Corn Producing Cry1Ac Toxins Does Not Adversely Affect Non-Target Arthropods

    PubMed Central

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The “sampling dates” had a significant effect on these indices, but no clear tendencies related to “Bt corn” or “sampling dates X corn variety” interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs. PMID:25437213

  12. 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

  13. Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects.

    PubMed

    Gonçalves, Heitor de Sá; Pontes, Maria Araci de Andrade; Bührer-Sékula, Samira; Cruz, Rossilene; Almeida, Paulo Cesar; Moraes, Maria Elisabete Amaral de; Penna, Gerson Oliveira

    2012-12-01

    This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT. PMID:23283457

  14. Prediction and diagnosis of clinical outcomes affecting restoration margins.

    PubMed

    Dennison, J B; Sarrett, D C

    2012-04-01

    The longevity of dental restorations is largely dependent on the continuity at the interface between the restorative material and adjacent tooth structure (the restoration margin). Clinical decisions on restoration repair or replacement are usually based upon the weakest point along that margin interface. Physical properties of a restorative material, such as polymerisation shrinkage, water sorption, solubility, elastic modulus and shear strength, all have an effect on stress distribution and can significantly affect margin integrity. This review will focus on two aspects of margin deterioration in the oral environment: the in vitro testing of margin seal using emersion techniques to simulate the oral environment and to predict clinical margin failure and the relationship between clinically observable microleakage and secondary caries. The many variables associated with in vitro testing of marginal leakage and the interpretation of the data are presented in detail. The most recent studies of marginal leakage mirror earlier methodology and lack validity and reliability. The lack of standardised testing procedures makes it impossible to compare studies or to predict the clinical performance of adhesive materials. Continual repeated in vitro studies contribute little to the science in this area. Clinical evidence is cited to refute earlier conclusions that clinical microleakage (penetrating margin discoloration) leads to caries development and is an indication for restoration replacement. Margin defects, without visible evidence of soft dentin on the wall or base of the defect, should be monitored, repaired or resealed, in lieu of total restoration replacement. PMID:22066463

  15. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival

    PubMed Central

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  16. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival.

    PubMed

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  17. Neonatal and fetal exposure to trans-fatty acid retards early growth and adiposity while adversely affecting glucose in mice

    PubMed Central

    Kavanagh, Kylie; Sajadian, Soraya; Jenkins, Kurt A.; Wilson, Martha D.; Carr, J. Jeffery; Wagner, Janice D.; Rudel, Lawrence L.

    2010-01-01

    Industrially produced trans fatty acids (TFAs) consumed in western diets are incorporated into maternal and fetal tissues, and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared to unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis we fed female C57/BL6 mice identical western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography), and glucose metabolism we assessed at weaning and adulthood. TFA exposure through breast milk caused significant early growth retardation (p<0.001) and higher fasting glucose (p=0.01) but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (p=0.02) may contribute to later catch-up growth, leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (p<0.05) and greater abdominal fat (p=0.01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. TFA surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. PMID:20650350

  18. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today. PMID:26573709

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... clinical 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...

  20. 45 CFR 60.11 - Reporting adverse actions on clinical privileges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... clinical 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...

  1. 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

  2. Interrater reliability of the modified Monitoring of Side Effects Scale for assessment of adverse effects of psychiatric medication in clinical and research settings.

    PubMed

    Nugent, Katie L; Spahr, Erin; Toroney, Jaimie; Mojtabai, Ramin; Nettles, Carrie; Turner, Lydia W; Fenton, Ashley; Spivak, Amethyst; Cullen, Bernadette A; Everett, Anita; Eaton, William W

    2015-06-01

    The assessment of adverse effects of psychiatric medications is important in clinical and research settings because they are often associated with medication discontinuation, symptom exacerbation, and reduced quality of life. Currently available assessment tools are either limited with regard to the number and variety of included adverse effects or are not practical for use in most clinical or research settings owing to specialized rater training required and administration length. This report describes a modification of the Monitoring of Side Effects Scale (MOSES), an established adverse effect rating scale, by adding severity anchors to improve its reliability and ease of use. Interrater reliability was good for 7 of the 8 bodily adverse effects assessed, with intraclass correlation coefficients ranging from 0.76 to 0.91 in a sample of patients with severe mental illness. This modified version of the Monitoring of Side Effects Scale holds promise as a useful tool for assessing medication adverse effects in clinical and research settings. PMID:25928700

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

    PubMed Central

    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. PMID:27326858

  4. 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. PMID:27326858

  5. Improving the Capture of Adverse Event Data in Clinical Trials: The Role of the International Atomic Energy Agency

    SciTech Connect

    Davidson, Susan E. Trotti, Andy; Ataman, Ozlem U.; Seong, Jinsil; Lau, Fen Nee; Motta, Neiro W. da; Jeremic, Branislav

    2007-11-15

    Purpose: To report meetings of the Applied Radiation Biology and Radiotherapy section of the International Atomic Energy Agency (IAEA), organized to discuss issues surrounding, and develop initiatives to improve, the recording of adverse events (AE) in clinical trials. Methods and Materials: A first meeting was held in Atlanta, GA (October 2004). A second meeting was held in Denver, CO (October 2005) and focused on AE data capture. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3 (CTCAE) was suggested during the first meeting as the preferred common platform for the collection and reporting of AE data in its clinical trials. The second meeting identified and reviewed the current weaknesses and variations in the capture of AE data, and proposals to improve the quality and consistency of data capture were discussed. Results: There is heterogeneity in the collection of AE data between both institutions and individual clinicians. The use of multiple scoring systems hampers comparisons of treatment outcomes between centers and trials. There is often insufficient detail on normal tissue treatment effects, which leads to an underestimate of toxicity. Implementation of improved data capture was suggested for one of the ongoing IAEA clinical trials. Conclusions: There is a need to compare the quality and completeness of data between institutions and the efficacy of structured/directed vs. traditional passive data collection. Data collection using the CTCAE (with or without a questionnaire) will be investigated in an IAEA multinational trial of radiochemotherapy and high-dose-rate brachytherapy in cervical cancer.

  6. Heterogeneity of major affective disorders. Biological and clinical evidence.

    PubMed

    Vita, A; Sacchetti, E; Conte, G; Alciati, A; Pennati, A

    1985-01-01

    In this paper we summarize the results of our recent and present research focused on analyzing the correlations between neurochemical, pharmacological and clinical parameters in patients with Major Depression. There is evidence that: a) pretreatment urinary MHPG is a useful predictor for clinical response to tricyclic antidepressants and to long-term lithium treatment; b) urinary MHPG is positively correlated to the age at onset of the disease; c) previous responses to tricyclics and age at onset of affective illness are supplementary tools for predicting the effectiveness of lithium and antidepressant drugs; d) platelet alpha-2-adrenoceptor density is inversely correlated with both urinary MHPG and age at onset; e) cerebral ventricular size is positively correlated with urinary MHPG and age at onset and may discriminate between patients with different outcomes on lithium prophylaxis; f) low MHPG excretors are more likely to have suffered from stressful life events in early childhood than normal-to-high excretors. Taken together, these results lend strong support to the hypothesis that Major Affective Disorder is a heterogeneous illness and that inherently different subgroups of affective patients can be recognized. PMID:2990848

  7. Clinical trials involving cats: What factors affect owner 1 participation?

    PubMed Central

    Gruen, Margaret E; Jiamachello, Katrina N; Thomson, Andrea; Lascelles, BDX

    2014-01-01

    Clinical trials are frequently hindered by difficulty recruiting eligible participants, increasing the timeline and limiting generalizability of results. In veterinary medicine, where proxy enrollment is required, no studies have detailed what factors influence owner participation in studies involving cats. We aimed to investigate these factors through a survey of owners at first opinion practices. The survey was designed using feedback from a pilot study and input from clinical researchers. Owners were asked demographic questions and whether they would, would not, or were unsure about participating in a clinical trial with their cat. They then ranked the importance and influence of various factors on participation using a 5-point Likert-type scale, and incentives from most to least encouraging. A total of 413 surveys were distributed to cat owners at four hospitals, two feline-only and two multi-species; 88.6% were completed. Data for importance and influence factors as well as incentive rankings were analyzed overall, by hospital type, location and whether owners would consider participating. The most influential factors were trust in the organization, benefit to the cat and veterinarian recommendation. Importance and influence factors varied by willingness to participate. Ranked incentives were not significantly different across groups, with “Free Services” ranked highest. This study provides a first look at what factors influence participation in clinical trials with cats. Given the importance placed in the recommendation of veterinarians, continued work is needed to determine veterinarian related factors affecting clinical trial participation. The results provide guidance towards improved clinical trial design, promotion and education. PMID:24938313

  8. Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study.

    PubMed

    Saridjan, Nathalie S; Huizink, Anja C; Koetsier, Jitske A; Jaddoe, Vincent W; Mackenbach, Johan P; Hofman, Albert; Kirschbaum, Clemens; Verhulst, Frank C; Tiemeier, Henning

    2010-02-01

    Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis. PMID:20006614

  9. Factors affecting clinical reasoning of occupational therapists: a qualitative study

    PubMed Central

    Shafaroodi, Narges; Kamali, Mohammad; Parvizy, Soroor; Mehraban, Afsoon Hassani; O’Toole, Giyn

    2014-01-01

    Background: Clinical reasoning is generally defined as the numerous modes of thinking that guide clinical practice but little is known about the factors affecting how occupational therapists manage the decision-making process. The aim of this qualitative study was to explore the factors influencing the clinical reasoning of occupational therapists. Methods: Twelve occupational therapy practitioners working in mental and physical dysfunction fields participated in this study. The sampling method was purposeful and interviews were continued until data saturation. All the interviews were recorded and transcribed. The data were analyzed through a qualitative content analysis method. Results: There were three main themes. The first theme: socio-cultural conditions included three subthemes: 1- client beliefs; 2- therapist values and beliefs; 3- social attitude to disability. The second theme: individual attributions included two subthemes 1- client attributions; 2- therapist attributions. The final theme was the workplace environment with the three subthemes: 1- knowledge of the managers of rehabilitation services, 2- working in an inter-professional team; 3- limited clinical facilities and resources. Conclusion: In this study, the influence of the attitudes and beliefs of client, therapist and society about illness, abilities and disabilities upon reasoning was different to previous studies. Understanding these factors, especially the socio-cultural beliefs basis can play a significant role in the quality of occupational therapy services. Accurate understanding of these influential factors requires more extensive qualitative and quantitative studies. PMID:25250253

  10. Morbid obesity in liver transplant recipients adversely affects longterm graft and patient survival in a single-institution analysis

    PubMed Central

    Conzen, Kendra D; Vachharajani, Neeta; Collins, Kelly M; Anderson, Christopher D; Lin, Yiing; Wellen, Jason R; Shenoy, Surendra; Lowell, Jeffrey A; Doyle, M B Majella; Chapman, William C

    2015-01-01

    Objective The effects of obesity in liver transplantation remain controversial. Earlier institutional data demonstrated no significant difference in postoperative complications or 1-year mortality. This study was conducted to test the hypothesis that obesity alone has minimal effect on longterm graft and overall survival. Methods A retrospective, single-institution analysis of outcomes in patients submitted to primary adult orthotopic liver transplantation was conducted using data for the period from 1 January 2002 to 31 December 2012. Recipients were divided into six groups by pre-transplant body mass index (BMI), comprising those with BMIs of <18.0 kg/m2, 18.0–24.9 kg/m2, 25.0–29.9 kg/m2, 30.0–35.0 kg/m2, 35.1–40.0 kg/m2 and >40 kg/m2, respectively. Pre- and post-transplant parameters were compared. A P-value of <0.05 was considered to indicate statistical significance. Independent predictors of patient and graft survival were determined using multivariate analysis. Results A total of 785 patients met the study inclusion criteria. A BMI of >35 kg/m2 was associated with non-alcoholic steatohepatitis (NASH) cirrhosis (P < 0.0001), higher Model for End-stage Liver Disease (MELD) score, and longer wait times for transplant (P = 0.002). There were no differences in operative time, intensive care unit or hospital length of stay, or perioperative complications. Graft and patient survival at intervals up to 3 years were similar between groups. Compared with non-obese recipients, recipients with a BMI of >40 kg/m2 showed significantly reduced 5-year graft (49.0% versus 75.8%; P < 0.02) and patient (51.3% versus 78.8%; P < 0.01) survival. Conclusions Obesity increasingly impacts outcomes in liver transplantation. Although the present data are limited by the fact that they were sourced from a single institution, they suggest that morbid obesity adversely affects longterm outcomes despite providing similar short-term results. Further analysis is

  11. Minimum Pricing of Alcohol versus Volumetric Taxation: Which Policy Will Reduce Heavy Consumption without Adversely Affecting Light and Moderate Consumers?

    PubMed Central

    Sharma, Anurag; Vandenberg, Brian; Hollingsworth, Bruce

    2014-01-01

    Background We estimate the effect on light, moderate and heavy consumers of alcohol from implementing a minimum unit price for alcohol (MUP) compared with a uniform volumetric tax. Methods We analyse scanner data from a panel survey of demographically representative households (n = 885) collected over a one-year period (24 Jan 2010–22 Jan 2011) in the state of Victoria, Australia, which includes detailed records of each household's off-trade alcohol purchasing. Findings The heaviest consumers (3% of the sample) currently purchase 20% of the total litres of alcohol (LALs), are more likely to purchase cask wine and full strength beer, and pay significantly less on average per standard drink compared to the lightest consumers (A$1.31 [95% CI 1.20–1.41] compared to $2.21 [95% CI 2.10–2.31]). Applying a MUP of A$1 per standard drink has a greater effect on reducing the mean annual volume of alcohol purchased by the heaviest consumers of wine (15.78 LALs [95% CI 14.86–16.69]) and beer (1.85 LALs [95% CI 1.64–2.05]) compared to a uniform volumetric tax (9.56 LALs [95% CI 9.10–10.01] and 0.49 LALs [95% CI 0.46–0.41], respectively). A MUP results in smaller increases in the annual cost for the heaviest consumers of wine ($393.60 [95% CI 374.19–413.00]) and beer ($108.26 [95% CI 94.76–121.75]), compared to a uniform volumetric tax ($552.46 [95% CI 530.55–574.36] and $163.92 [95% CI 152.79–175.03], respectively). Both a MUP and uniform volumetric tax have little effect on changing the annual cost of wine and beer for light and moderate consumers, and likewise little effect upon their purchasing. Conclusions While both a MUP and a uniform volumetric tax have potential to reduce heavy consumption of wine and beer without adversely affecting light and moderate consumers, a MUP offers the potential to achieve greater reductions in heavy consumption at a lower overall annual cost to consumers. PMID:24465368

  12. An evidence-based laparoscopic simulation curriculum shortens the clinical learning curve and reduces surgical adverse events

    PubMed Central

    De Win, Gunter; Van Bruwaene, Siska; Kulkarni, Jyotsna; Van Calster, Ben; Aggarwal, Rajesh; Allen, Christopher; Lissens, Ann; De Ridder, Dirk; Miserez, Marc

    2016-01-01

    Background Surgical simulation is becoming increasingly important in surgical education. However, the method of simulation to be incorporated into a surgical curriculum is unclear. We compared the effectiveness of a proficiency-based preclinical simulation training in laparoscopy with conventional surgical training and conventional surgical training interspersed with standard simulation sessions. Materials and methods In this prospective single-blinded trial, 30 final-year medical students were randomized into three groups, which differed in the way they were exposed to laparoscopic simulation training. The control group received only clinical training during residency, whereas the interval group received clinical training in combination with simulation training. The Center for Surgical Technologies Preclinical Training Program (CST PTP) group received a proficiency-based preclinical simulation course during the final year of medical school but was not exposed to any extra simulation training during surgical residency. After 6 months of surgical residency, the influence on the learning curve while performing five consecutive human laparoscopic cholecystectomies was evaluated with motion tracking, time, Global Operative Assessment of Laparoscopic Skills, and number of adverse events (perforation of gall bladder, bleeding, and damage to liver tissue). Results The odds of adverse events were 4.5 (95% confidence interval 1.3–15.3) and 3.9 (95% confidence interval 1.5–9.7) times lower for the CST PTP group compared with the control and interval groups. For raw time, corrected time, movements, path length, and Global Operative Assessment of Laparoscopic Skills, the CST PTP trainees nearly always started at a better level and were never outperformed by the other trainees. Conclusion Proficiency-based preclinical training has a positive impact on the learning curve of a laparoscopic cholecystectomy and diminishes adverse events. PMID:27512343

  13. Clinical factors affecting quality of life of patients with asthma

    PubMed Central

    Uchmanowicz, Bartosz; Panaszek, Bernard; Uchmanowicz, Izabella; Rosińczuk, Joanna

    2016-01-01

    Background In recent years, there has been increased interest in the subjective quality of life (QoL) of patients with bronchial asthma. QoL is a significant indicator guiding the efforts of professionals caring for patients, especially chronically ill ones. The identification of factors affecting the QoL reported by patients, despite their existing condition, is important and useful to provide multidisciplinary care for these patients. Aim To investigate the clinical factors affecting asthma patients’ QoL. Methods The study comprised 100 patients (73 female, 27 male) aged 18–84 years (mean age was 45.7) treated in the Allergy Clinic of the Wroclaw Medical University Department and Clinic of Internal Diseases, Geriatrics and Allergology. All asthma patients meeting the inclusion criteria were invited to participate. Data on sociodemographic and clinical variables were collected. In this study, we used medical record analysis and two questionnaires: the Asthma Quality of Life Questionnaire (AQLQ) to assess the QoL of patients with asthma and the Asthma Control Test to measure asthma control. Results Active smokers were shown to have a significantly lower QoL in the “Symptoms” domain than nonsmokers (P=0.006). QoL was also demonstrated to decrease significantly as the frequency of asthma exacerbations increased (R=−0.231, P=0.022). QoL in the domain “Activity limitation” was shown to increase significantly along with the number of years of smoking (R=0.404; P=0.004). Time from onset and the dominant symptom of asthma significantly negatively affected QoL in the “Activity limitation” domain of the AQLQ (R=−0.316, P=0.001; P=0.029, respectively). QoL scores in the “Emotional function” and “Environmental stimuli” subscale of the AQLQ decreased significantly as time from onset increased (R=−0.200, P=0.046; R=−0.328, P=0.001, respectively). Conclusion Patients exhibiting better symptom control have higher QoL scores. Asthma patients’ Qo

  14. Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype

    PubMed Central

    Bodden, Carina; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Gerß, Joachim; Palme, Rupert; Lesch, Klaus-Peter; Lewejohann, Lars; Kaiser, Sylvia; Sachser, Norbert

    2015-01-01

    Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered

  15. 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

  16. Adverse metabolic effects of dietary fructose: Results from recent epidemiological, clinical, and mechanistic studies

    PubMed Central

    Stanhope, Kimber L.; Schwarz, Jean-Marc; Havel, Peter J.

    2014-01-01

    Purpose of review The effects of dietary sugar on risk factors and processes associated with metabolic disease remains a controversial topic, with recent reviews of the available evidence arriving at widely discrepant conclusions. Recent findings There are many recently published epidemiological studies that provide evidence that sugar consumption is associated with metabolic disease. Three recent clinical studies, which investigated the effects of consuming relevant doses of sucrose or high fructose corn syrup along with ad libitum diets, provide evidence that consumption of these sugars increase risk factors for cardiovascular disease (CVD) and metabolic syndrome. Mechanistic studies suggest that these effects result from the rapid hepatic metabolism of fructose catalyzed by fructokinase C, which generates substrate for de novo lipogenesis and leads to increased uric acid levels. Recent clinical studies investigating the effects of consuming less sugar, via educational interventions or by substitution of sugar-sweetened beverages for non-calorically sweetened beverages, provide evidence that such strategies have beneficial effects on risk factors for metabolic disease or on BMI in children. Summary The accumulating epidemiological evidence, direct clinical evidence, and the evidence suggesting plausible mechanisms support a role for sugar in the epidemics of metabolic syndrome, CVD and type 2 diabetes. PMID:23594708

  17. Intervention Effects on Negative Affect of CPS-Referred Children: Results of a Randomized Clinical Trial

    PubMed Central

    Lind, Teresa; Bernard, Kristin; Ross, Emily; Dozier, Mary

    2014-01-01

    Exposure to early adversity places young children at risk for behavioral, physiological, and emotional dysregulation, predisposing them to a range of long-term problematic outcomes. Attachment and Biobehavioral Catch-up (ABC) is a 10-session intervention designed to enhance children’s self-regulatory capabilities by helping parents to behave in nurturing, synchronous, and non-frightening ways. The effectiveness of the intervention was assessed in a randomized clinical trial, with parents who had been referred to Child Protective Services (CPS) for allegations of maltreatment. Parent-child dyads received either the ABC intervention or a control intervention. Following the intervention, children from the ABC intervention (n = 56) expressed lower levels of negative affect during a challenging task compared to children from the control intervention (n = 61). PMID:24814751

  18. Intervention effects on negative affect of CPS-referred children: results of a randomized clinical trial.

    PubMed

    Lind, Teresa; Bernard, Kristin; Ross, Emily; Dozier, Mary

    2014-09-01

    Exposure to early adversity places young children at risk for behavioral, physiological, and emotional dysregulation, predisposing them to a range of long-term problematic outcomes. Attachment and Biobehavioral Catch-up (ABC) is a 10-session intervention designed to enhance children's self-regulatory capabilities by helping parents to behave in nurturing, synchronous, and non-frightening ways. The effectiveness of the intervention was assessed in a randomized clinical trial, with parents who had been referred to Child Protective Services (CPS) for allegations of maltreatment. Parent-child dyads received either the ABC intervention or a control intervention. Following the intervention, children from the ABC intervention (n=56) expressed lower levels of negative affect during a challenging task compared to children from the control intervention (n=61). PMID:24814751

  19. Mitigation of Adverse Clinical Events of a Narrow Target Therapeutic Index Compound through Modified Release Formulation Design: An in Vitro, in Vivo, in Silico, and Clinical Pharmacokinetic Analysis.

    PubMed

    Good, David J; Hartley, Ruiling; Mathias, Neil; Crison, John; Tirucherai, Giridhar; Timmins, Peter; Hussain, Munir; Haddadin, Raja; Koo, Otilia; Nikfar, Faranak; Fung, Nga Kit Eliza

    2015-12-01

    BMS-914392 is a tricyclic pyranoquinoline BCS class 2 weak base that demonstrates high solubility in low pH environments. Initial clinical studies indicated that rapid release of high dose BMS-914392 led to transient adverse events associated with peak plasma concentrations. A modified release (MR) formulation strategy was proposed to suppress the peak blood concentration and maintain total exposure to overcome the adverse effects. Three modified release prototype formulations were developed and tested via a USP 3 dissolution method to verify that each formulation can effectively slow the release of BMS-914392. A pharmacokinetic (PK) absorption model was employed to guide the formulation development and selection. Simulations showed good agreement with plasma levels measured after oral dosing in dogs. Identification of key formulation factors to achieve release rates suitable for blunting peak blood levels without diminishing exposure were achieved through combined preclinical data and use of GastroPlus simulations. PK absorption model refinements based on phase 1 data, dog pharmacokinetic results, and in vitro data provided reliable predictions of human absorption profiles and variability in patients. All three prototype formulations demonstrated lower maximum plasma concentrations of BMS-914392 and maintained satisfactory relative bioavailability. Both the PK absorption model and subsequent clinical data indicated that an acidified hydrophilic matrix MR formulation had the greatest potential to reduce the incidence of adverse events and showed the best exposure profile in fasted state healthy subjects with and without famotidine coadministration. The risk based development process achieved successful screening and selection of a suitable modified release formulation to enable clinical efficacy trials. PMID:26536519

  20. Clinically Inconsequential Alerts: The Characteristics of Opioid Drug Alerts and Their Utility in Preventing Adverse Drug Events in the Emergency Department

    PubMed Central

    Genco, Emma K.; Forster, Jeri E.; Flaten, Hanna; Goss, Foster; Heard, Kennon J.; Hoppe, Jason; Monte, Andrew A.

    2016-01-01

    Study objective We examine the characteristics of clinical decision support alerts triggered when opioids are prescribed, including alert type, override rates, adverse drug events associated with opioids, and preventable adverse drug events. Methods This was a retrospective chart review study assessing adverse drug event occurrences for emergency department (ED) visits in a large urban academic medical center using a commercial electronic health record system with clinical decision support. Participants include those aged 18 to 89 years who arrived to the ED every fifth day between September 2012 and January 2013. The main outcome was characteristics of opioid drug alerts, including alert type, override rates, opioid-related adverse drug events, and adverse drug event preventability by clinical decision support. Results Opioid drug alerts were more likely to be overridden than nonopioid alerts (relative risk 1.35; 95% confidence interval [CI] 1.21 to 1.50). Opioid drug-allergy alerts were twice as likely to be overridden (relative risk 2.24; 95% CI 1.74 to 2.89). Opioid duplicate therapy alerts were 1.57 times as likely to be overridden (95% CI 1.30 to 1.89). Fourteen of 4,581 patients experienced an adverse drug event (0.31%; 95% CI 0.15% to 0.47%), and 8 were due to opioids (57.1%). None of the adverse drug events were preventable by clinical decision support. However, 46 alerts were accepted for 38 patients that averted a potential adverse drug event. Overall, 98.9% of opioid alerts did not result in an actual or averted adverse drug event, and 96.3% of opioid alerts were overridden. Conclusion Overridden opioid alerts did not result in adverse drug events. Clinical decision support successfully prevented adverse drug events at the expense of generating a large volume of inconsequential alerts. To prevent 1 adverse drug event, providers dealt with more than 123 unnecessary alerts. It is essential to refine clinical decision support alerting systems to eliminate

  1. Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients.

    PubMed

    Dorer, David J; Knickerbocker, Ronald K; Baccarani, Michele; Cortes, Jorge E; Hochhaus, Andreas; Talpaz, Moshe; Haluska, Frank G

    2016-09-01

    Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671) to determine the impact of ponatinib dose intensity on the following adverse events: arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events), venous thromboembolic events, cardiac failure, thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase, increased alanine aminotransferase, increased aspartate aminotransferase, rash, arthralgia, and hypertriglyceridemia. Multivariate analyses allowed adjustment for covariates potentially related to changes in dosing or an event. Logistic regression analysis identified significant associations between dose intensity and most events after adjusting for covariates. Pancreatitis, rash, and cardiac failure had the strongest associations with dose intensity (odds ratios >2). Time-to-event analyses showed significant associations between dose intensity and risk of arterial occlusive events and each subcategory. Further, these analyses suggested that a lag exists between a change in dose and the resulting change in event risk. No significant association between dose intensity and risk of venous thromboembolic events was evident. Collectively, these findings suggest a potential causal relationship between ponatinib dose and certain adverse events and support prospective investigations of approaches to lower average ponatinib dose intensity. PMID:27505637

  2. Task-Oriented and Bottle Feeding Adversely Affect the Quality of Mother-Infant Interactions Following Abnormal Newborn Screens

    PubMed Central

    Tluczek, Audrey; Clark, Roseanne; McKechnie, Anne Chevalier; Orland, Kate Murphy; Brown, Roger L.

    2010-01-01

    Objective Examine effects of newborn screening (NBS) and neonatal diagnosis on the quality of mother-infant interactions in the context of feeding. Methods Study compared the quality of mother-infant feeding interactions among four groups of infants classified by severity of NBS and diagnostic results: cystic fibrosis (CF), congenital hypothyroidism, heterozygote CF carrier, and healthy with normal NBS. The Parent-Child Early Relational Assessment and a task-oriented item measured the quality of feeding interactions for 130 dyads, infant ages 3–19 weeks (M=9.19, SD=3.28). The Center for Epidemiologic Studies Depression Scale and State-Trait Anxiety Inventory measured maternal depression and anxiety. Results Composite Indicator Structure Equation Modeling showed that infant diagnostic status and, to a lesser extent, maternal education predicted feeding method. Mothers of infants with CF were most likely to bottle feed, which was associated with more task-oriented maternal behavior than breastfeeding. Mothers with low task-oriented behavior showed more sensitivity and responsiveness to infant cues, as well as less negative affect and behavior in their interactions with their infants than mothers with high task-oriented scores. Mothers of infants with CF were significantly more likely to have clinically significant anxiety and depression than the other groups. However, maternal psychological profile did not predict feeding method or interaction quality. Conclusions Mothers in the CF group were the least likely to breastfeed. Research is needed to explicate long-term effects of feeding methods on quality of mother-child relationship and ways to promote continued breastfeeding following a neonatal CF diagnosis. PMID:20495477

  3. Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials

    PubMed Central

    Keating, C; Ewart, L; Grundy, L; Valentin, JP; Grundy, D

    2014-01-01

    Background Motility-related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development. Methods Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility-related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration-response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model. Key Results Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%. Conclusions & Inferences Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility. PMID:24813024

  4. Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis

    PubMed Central

    Srihawan, Chanunya; Castelblanco, Rodrigo Lopez; Salazar, Lucrecia; Wootton, Susan H.; Aguilera, Elizabeth; Ostrosky-Zeichner, Luis; Sandberg, David I.; Choi, HuiMahn A.; Lee, Kiwon; Kitigawa, Ryan; Tandon, Nitin; Hasbun, Rodrigo

    2016-01-01

    Background. Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods. We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening cerebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results. A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31–18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27–7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51–18.92; P = .01) were associated with an adverse outcome. Conclusions. Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. PMID:27419154

  5. Clinical factors affecting the timing of delivery in twin pregnancies

    PubMed Central

    Lee, Chae Min; Yang, Sun Hye; Lee, Sun Pyo; Hwang, Byung Chul

    2014-01-01

    Objective To investigate clinical factors affecting the timing of delivery in twin pregnancies in order to minimize perinatal complications. Methods A retrospective study involved 163 twin pregnancies delivered from January 2006 to September 2011 at Gachon University Gil Medical Center. These cases were divided into three groups based on the delivery timing: less than 32 weeks' gestation (group A), between 32 and 35+6 weeks' gestation (group B), and over 36 weeks' gestation (group C). Clinical factors including maternal age, parity, presence of premature uterine contraction, presence of premature rupture of membrane, white blood cell, high sensitive C-reactive protein level, cervical dilatation, maternal complication, chorionicity, twin specific complication, and perinatal complication were analyzed for each group. Results In group B, the timing of delivery was postponed for 14 days or more from the time of admission, and there were fewer numbers of babies with low Apgar score at birth compared with other groups. The frequency of uterine contraction (P<0.001), presence of premature rupture of membranes (P=0.017), dilatation of cervix (P<0.001), increased white blood cell and high sensitive C-reactive protein levels (P=0.002, P<0.001) were important clinical factors during decision making process of delivery timing in twin pregnancies. Twin specific fetal conditions, such as twin-twin transfusion syndrome and discordant growth (over 25% or more) were shown more frequently in group A. However, there were no significant statistical differences among three groups (P=0.06, P=0.14). Conclusion Proper management for preventing premature contraction and inflammation can be essential in twin pregnancies until 32 weeks' gestation, and may decrease maternal and perinatal complications. PMID:25469330

  6. Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

    PubMed Central

    Servitja, Sonia; Martos, Tamara; Rodriguez Sanz, Maria; Garcia-Giralt, Natalia; Prieto-Alhambra, Daniel; Garrigos, Laia; Nogues, Xavier

    2015-01-01

    Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables. PMID:26327926

  7. Adverse effects in 5 patients receiving EDTA at an outpatient chelation clinic.

    PubMed

    Morgan, Brent W; Kori, Singleton; Thomas, Jerry D

    2002-10-01

    Despite limited scientific evidence, Na2EDTA chelation therapy has been advocated for a variety of conditions including atherosclerosis. Five patients presented with symptoms that developed 30 min-2 h into chelation therapy at an outpatient clinic with infusions of sterile waterwith 3 g Na2EDTA, 2 g MgCl, 100 mg B12, 100 mg B6, 1 ml bit B complex and 15 g Vit C; 1 patient also received 10 ml of 50% DMSO iv. All patients experienced gastrointestinal and musculoskeletal symptoms. Additional effects were (4/5), excessive thirst (4/5), and diaphoresis (4/5). On presentation patients were hypotensive (5/5), tachycardic (4/5) and febrile (5/5). Therapy included iv. fluids (5/5), dopamine (1/5), and ivantibiotics (4/5). Initial data showed leukopenia (5/5), thrombocytopenia (3/5), bandemia (4/5), EKG abnormalities of unknown acuity (5/5), and transient, mild rise in serum creatinine (3/4). All patients were discharged without permanent sequelae. It is unclear if effects were related to dose or rate of administration. PMID:12361109

  8. Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

    PubMed Central

    Espe, Katharina M.; Raila, Jens; Henze, Andrea; Blouin, Katja; Schneider, Andreas; Schmiedeke, Daniel; Krane, Vera; Pilz, Stefan; Schweigert, Florian J.; Hocher, Berthold; Wanner, Christoph

    2013-01-01

    Summary Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75–3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89–1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. PMID:23335039

  9. CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes

    PubMed Central

    Himoto, Yuki; Kido, Aki; Moribata, Yusaku; Yamaoka, Toshihide; Okumura, Ryosuke; Togashi, Kaori

    2015-01-01

    Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings. PMID:26937442

  10. CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes.

    PubMed

    Himoto, Yuki; Kido, Aki; Moribata, Yusaku; Yamaoka, Toshihide; Okumura, Ryosuke; Togashi, Kaori

    2015-01-01

    Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings. PMID:26937442

  11. Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

    PubMed Central

    George, Anish; Bhatia, Raghav T.; Buchanan, Gill L.; Whiteside, Anne; Moisey, Robert S.; Beer, Stephen F.; Chattopadhyay, Sudipta; Sathyapalan, Thozhukat; John, Joseph

    2015-01-01

    Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. PMID:26571120

  12. Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: beyond bleeding complications.

    PubMed

    Raschi, Emanuel; Bianchin, Matteo; Ageno, Walter; De Ponti, Roberto; De Ponti, Fabrizio

    2016-08-25

    Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered the market in 2008 with the expected breakthrough potential of circumventing limitations related to treatment with vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although data derived from premarketing randomized clinical trials have largely demonstrated the clinical benefit of DOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safety in the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy, in order to assess the actual risk-benefit profile. In this critical review, we aimed to evaluate the evidence on the latest debated safety issues. In the first section, we will discuss: 1) the need for pharmacovigilance (ie, the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems in the real-world setting), and 2) the importance of properly interpreting postmarketing data to avoid unnecessary alarm. In the second section, emerging and debated safety issues potentially associated with the use of DOACs in the postmarketing setting will be assessed: 1) the potential coronary risk (which emerged during the preapproval period); 2) the occurrence of liver injury (a risk undetected in clinical trials and highlighted by case reports or series); and 3) the potential for renal damage (a still unclear safety issue). It is anticipated that hepatic and renal issues still require dedicated postauthorization safety studies to ultimately assess causality. PMID:27578223

  13. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series.

    PubMed

    Buchan, Sarah; Muldoon, Katherine A; Spaans, Johanna N; Balfour, Louise; Samson, Lindy; Walker, Mark; Cameron, D William

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990-2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990-2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03-1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12-6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04-1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30-40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  14. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series

    PubMed Central

    Buchan, Sarah; Spaans, Johanna N.; Balfour, Louise

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990–2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990–2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03–1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12–6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04–1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30–40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  15. Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: the Mayo Clinic approach

    PubMed Central

    ZENT, CLIVE S.; KAY, NEIL E.

    2012-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with early–intermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ‘good leukemia’ with a predictably ‘benign’ outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome. PMID:21649549

  16. When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience.

    PubMed

    Lesch, Klaus-Peter

    2011-01-01

    Although converging epidemiological evidence links exposure to stressful life events with increased risk for affective spectrum disorders, there is extraordinary interindividual variability in vulnerability to adversity. The environmentally moderated penetrance of genetic variation is thought to play a major role in determining who will either develop disease or remain resilient. Research on genetic factors in the aetiology of disorders of emotion regulation has, nevertheless, been complicated by a mysterious discrepancy between high heritability estimates and a scarcity of replicable gene-disorder associations. One explanation for this incongruity is that at least some specific gene effects are conditional on environmental cues, i.e. gene-by-environment interaction (G × E) is present. For example, a remarkable number of studies reported an association of variation in the human serotonin (5-HT) transporter gene (SLC6A4, 5-HTT, SERT) with emotional and cognitive traits as well as increased risk for depression in interaction with psychosocial adversity. The results from investigations in non-human primate and mouse support the occurrence of G × E interaction by showing that variation of 5-HTT function is associated with a vulnerability to adversity across the lifespan leading to unfavourable outcomes resembling various neuropsychiatric disorders. The neural and molecular mechanisms by which environmental adversity in early life increases disease risk in adulthood are not known but may include epigenetic programming of gene expression during development. Epigenetic mechanisms, such as DNA methylation and chromatin modification, are dynamic and reversible and may also provide targets for intervention strategies (see Bountra et al., Curr Top Behav Neurosci, 2011). Animal models amenable to genetic manipulation are useful in the identification of molecular mechanisms underlying epigenetic programming by adverse environments and individual differences in

  17. Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management

    PubMed Central

    Tarhini, Ahmad

    2013-01-01

    Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been shown to extend overall survival (OS) in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling with ipilimumab prolongs T-cell activation and restores T-cell proliferation, thus amplifying T-cell-mediated immunity and the patient's capacity to mount an effective antitumor immune response. While this immunostimulation has unprecedented OS benefits in the melanoma setting, it can also result in immune-mediated effects on various organ systems, leading to immune-related adverse events (irAEs). Ipilimumab-associated irAEs are common and typically low grade and manageable, but can also be serious and life threatening. The skin and gastrointestinal tract are most frequently affected, while hepatic, endocrine, and neurologic events are less common. With proper management, most irAEs resolve within a relatively short time, with a predictable resolution pattern. Prompt and appropriate management of these irAEs is essential and treatment guidelines have been developed to assist oncologists and their teams. Implementation of these irAE management algorithms will help ensure that patients are able to benefit from ipilimumab therapy with adequate control of toxicities. PMID:24278787

  18. The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular function, and survival in Medaka (Oryzias latipes) embryos.

    PubMed Central

    Colman, Jamie R; Ramsdell, John S

    2003-01-01

    Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The toxins are lipophilic polyether toxins that elicit a myriad of effects depending on the route of exposure and the target organism. Brevetoxins are therefore broadly toxic to marine and estuarine animals. By mimicking the maternal route of exposure to the oocytes in finfish, we characterized the adverse effects of the type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the experimental model in which individual eggs were exposed via microinjection to various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic twitches in the form of sustained convulsions, spinal curvature, clumping of the erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin were often unable to hatch in the classic tail-first fashion and emerged head first, which resulted in partial hatches and death. We determined that the LD(50) (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0 ng/egg. The results of this study complement previous studies of the developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by illustrating in vivo the differing affinities of the two congeners for cardiac sodium channels. Consequently, we observed differing cardiovascular responses in the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia, whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was delayed. PMID:14644667

  19. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-{beta}1

    SciTech Connect

    Schmid, Stephan A. . E-mail: leoni.kunz-schughart@oncoray.de; Gaumann, Andreas; Wondrak, Marit; Eckermann, Christoph; Schulte, Stephanie; Mueller-Klieser, Wolfgang; Wheatley, Denys N.; Kunz-Schughart, Leoni A.

    2007-07-15

    When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-{beta}1, which also shows anti-angiogenic activity in the model. Both TGF-{beta}1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-{beta}1 neutralization, indicating a causal relationship between lactate and TGF-{beta}1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

  20. A Computational Study on the Effects of Dynamic Roughness Application to Separated Transitional Flows Affected by Adverse Pressure Gradient

    NASA Astrophysics Data System (ADS)

    Campitelli, Gennaro

    The study of transitional flows is considered crucial for many practical engineering applications. In fact, a comprehensive understanding of the laminar-turbulent transition phenomenon often helps to improve the overall performance of apparatuses such as airfoils, wind turbines, hulls and turbomachinery blades. In addition to understanding and prediction of transitional flows, active research continues in the area of boundary layer control, which includes control of phenomena such as flow separation and transition. For instance, optimum geometrical shaping may be followed by the adoption on the wall-surface of riblets to adjust pressure gradient and reduce drag. Further "flow control" may also be acquired by introducing active devices able to modify the flow field in order to accomplish a desired aerodynamic task. Such flow manipulation is often achieved by using time-dependent forcing mechanisms which promote natural instabilities amplifying the control effectiveness. Localized energy inputs such as Lorentz-force actuator, piezoelectric flaps and synthetic jets all produce a consistent boundary layer mixing enhancement with lift increase and drag abatement. The current numerical study attempts to demonstrate the efficacy of dynamic roughness (DR) on altering separated-reattached transitional flows under adverse pressure gradient. It has already been proven how DR, acting on the boundary sublayer perturbation, is able to suppress (partially or completely) the typical leading edge separation for an airfoil at different angles of attack. This makes DR particularly suitable for separated flow control applications where the shear layer reattaches presenting the characteristic laminar separation bubble. A numerical sensitivity study has been conducted with an efficient orthogonal design taking into account four different control parameters on three levels (actuation frequency, humps height, rows displacement, synchronization) to provide an optimum DR setup which limits

  1. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  2. GENETIC POLYMORPHISMS AFFECTING SUSCEPTIBILITY TO MERCURY NEUROTOXICITY IN CHILDREN: SUMMARY FINDINGS FROM THE CASA PIA CHILDREN's AMALGAM CLINICAL TRIAL

    PubMed Central

    Woods, James S.; Heyer, Nicholas J.; Russo, Joan E.; Martin, Michael D.; Farin, Federico M.

    2014-01-01

    Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic predisposition. We examined the possibility that common genetic variants that are known to affect neurologic functions or Hg handling in adults would modify the adverse neurobehavioral effects of Hg exposure in children. Three hundred thirty subjects who participated as children in the recently completed Casa Pia Clinical Trial of Dental Amalgams in Children were genotyped for 27 variants of 13 genes that are reported to affect neurologic functions and/or Hg disposition in adults. Urinary Hg concentrations, reflecting Hg exposure from any source, served as the Hg exposure index. Regression modeling strategies were employed to evaluate potential associations between allelic status for individual genes or combinations of genes, Hg exposure, and neurobehavioral test outcomes assessed at baseline and for 7 subsequent years during the clinical trial. Among boys, significant modification of Hg effects on neurobehavioral outcomes over a broad range of neurologic domains was observed with variant genotypes for 4 of 13 genes evaluated. Modification of Hg effects on a more limited number of neurobehavioral outcomes was also observed for variants of another 8 genes. Cluster analyses suggested some genes interacting in common processes to affect Hg neurotoxicity. In contrast, significant modification of Hg effects on neurobehavioral functions among girls with the same genotypes was substantially more limited. These observations suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children, particularly boys, with genetic variants that are relatively common to the general human population. These findings advance public health goals to identify factors underlying susceptibility to Hg toxicity and may contribute to strategies for preventing

  3. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis

    PubMed Central

    Cho, Kyoung Im; Cho, Sang Hoon; Her, Ae-Young; Singh, Gillian Balbir; Shin, Eun-Seok

    2016-01-01

    Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS. PMID:27548384

  4. Clinical factors affecting pathological fracture and healing of unicameral bone cysts

    PubMed Central

    2014-01-01

    Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

  5. Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

    PubMed Central

    Kol, Amir; Murphy, Brian; Walker, Naomi J.; Wood, Joshua A.; Clark, Kaitlin; Verstraete, Frank J.M.; Borjesson, Dori L.

    2015-01-01

    Abstract Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that∼50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients. PMID:25404388

  6. Overexpression of the Promigratory and Prometastatic PTK7 Receptor Is Associated with an Adverse Clinical Outcome in Colorectal Cancer

    PubMed Central

    Boher, Jean-Marie; Monges, Geneviève; Castellano, Rémy; Goubard, Armelle; Doremus, Marie; Poizat, Flora; Lelong, Bernard; de Chaisemartin, Cécile; Bardin, Florence; Viens, Patrice; Raoul, Jean-Luc; Prebet, Thomas; Aurrand-Lions, Michel; Borg, Jean-Paul; Gonçalves, Anthony

    2015-01-01

    Biomarkers and novel therapeutic targets are urgently needed in colorectal cancer (CRC). The pseudo tyrosine kinase receptor 7 (PTK7) is involved in planar cell polarity and it is deregulated in various malignancies, including CRC. Yet, little is known about its protein expression in human CRC, or about a possible correlation of its expression with clinical endpoints. Using a clinically annotated Tissue MicroArray (TMA) produced from from 192 consecutive CRC patients treated by initial surgery, we examined PTK7 expression by immunohistochemistry in tumoral tissue and matched normal mucosae, and correlated its expression with clinico-pathological features and patient outcome. PTK7 depletion by specific shRNA in HCT116 and HCT15 CRC cell lines was found to affect cell proliferation, resistance to drugs and cell migration. Tumor growth and metastatic phenotype were investigated in vivo using a xenograft mouse model of CRC cells with modulated expression of PTK7 levels. PTK7 was significantly up-regulated in CRC tissue as compared to matched healthy mucosae, and significant overexpression was found in 34% of patients. PTK7 overexpression was significantly associated with a reduced metastasis-free survival in non-metastatic patients. In HCT116 and HCT15 cells, shRNA PTK7 reduced migration but did not affect cell proliferation and resistance to drugs. In a xenograft mouse of HCT15 cells, downregulation of PTK7 led to reduced tumor growth, whereas its overexpression in PTK7-negative cancer cells led to increased metastatic events. PTK7 expression thus represents a potential prognostic biomarker and a novel therapeutic target in CRC. PMID:25962058

  7. Do Case Rates Affect Physicians' Clinical Practice in Radiation Oncology?: An Observational Study

    PubMed Central

    Loy, Bryan A.; Shkedy, Clive I.; Powell, Adam C.; Happe, Laura E.; Royalty, Julie A.; Miao, Michael T.; Smith, Gary L.; Long, James W.; Gupta, Amit K.

    2016-01-01

    Case rate payments combined with utilization monitoring may have the potential to improve the quality of care by reducing over and under-treatment. Thus, a national managed care organization introduced case rate payments at one multi-site radiation oncology provider while maintaining only fee-for-service payments at others. This study examined whether the introduction of the payment method had an effect on radiation fractions administered when compared to clinical guidelines. The number of fractions of radiation therapy delivered to patients with bone metastases, breast, lung, prostate, and skin cancer was assessed for concordance with clinical guidelines. The proportion of guideline-based care ascertained from the payer's claims database was compared before (2011) and after (2013) the payment method introduction using relative risks (RR). After the introduction of case rates, there were no significant changes in guideline-based care in breast, lung, and skin cancer; however, patients with bone metastases and prostate cancer were significantly more likely to have received guideline-based care (RR = 2.0 and 1.1, respectively, p<0.05). For the aggregate of all cancers, the under-treatment rate significantly declined (p = 0.008) from 4% to 0% after the introduction of case rate payments, while the over-treatment rate remained steady at 9%, with no significant change (p = 0.20). These findings suggest that the introduction of case rate payments did not adversely affect the rate of guideline-based care at the provider examined. Additional research is needed to isolate the effect of the payment model and assess implications in other populations. PMID:26870963

  8. Do Case Rates Affect Physicians' Clinical Practice in Radiation Oncology?: An Observational Study.

    PubMed

    Loy, Bryan A; Shkedy, Clive I; Powell, Adam C; Happe, Laura E; Royalty, Julie A; Miao, Michael T; Smith, Gary L; Long, James W; Gupta, Amit K

    2016-01-01

    Case rate payments combined with utilization monitoring may have the potential to improve the quality of care by reducing over and under-treatment. Thus, a national managed care organization introduced case rate payments at one multi-site radiation oncology provider while maintaining only fee-for-service payments at others. This study examined whether the introduction of the payment method had an effect on radiation fractions administered when compared to clinical guidelines. The number of fractions of radiation therapy delivered to patients with bone metastases, breast, lung, prostate, and skin cancer was assessed for concordance with clinical guidelines. The proportion of guideline-based care ascertained from the payer's claims database was compared before (2011) and after (2013) the payment method introduction using relative risks (RR). After the introduction of case rates, there were no significant changes in guideline-based care in breast, lung, and skin cancer; however, patients with bone metastases and prostate cancer were significantly more likely to have received guideline-based care (RR = 2.0 and 1.1, respectively, p<0.05). For the aggregate of all cancers, the under-treatment rate significantly declined (p = 0.008) from 4% to 0% after the introduction of case rate payments, while the over-treatment rate remained steady at 9%, with no significant change (p = 0.20). These findings suggest that the introduction of case rate payments did not adversely affect the rate of guideline-based care at the provider examined. Additional research is needed to isolate the effect of the payment model and assess implications in other populations. PMID:26870963

  9. Studies of foetuses from cows clinically affected with bovine leucosis.

    PubMed

    Kono, Y; Sentsui, H; Arai, K; Irishio, W; Fujigaki, A

    1983-10-01

    Five foetuses at varying stages of gestation were recovered from cows showing clinical signs of infection with bovine leukaemia virus (BLV). No pathological changes were found in the foetuses although BLV was isolated from 2 of these foetuses. No antibody to BLV could be detected by virus-neutralisation or immunodiffusion (ID) techniques in these two foetuses, although neutralising antibody alone was detected in one of the other 3 foetuses which were all negative for virus. PMID:6316629

  10. Patient characteristics affecting attendance at general outpatient clinics.

    PubMed Central

    McClure, R J; Newell, S J; Edwards, S

    1996-01-01

    A study was carried out to identify the characteristics of children who do not attend appointments at general outpatient clinics. Over six months, 359 children who had an appointment at a general clinic were studied using a questionnaire given to parents (74% response rate) and by inspection of case notes. Based on their first appointment in the study period, children were divided into 'attenders' (n = 262) and 'non-attenders' (n = 97) for analysis. Non-attenders were significantly more likely to have one or more of the following characteristics: lower social class, poorer housing, unmarried parent(s) (56% v 33%), longer journey to clinic (35 v 27.6 minutes), more appointments per year (4.2 v 3.3), poorer past attendance record, and received their appointment by post (76% v 44%). Surprisingly parents of non-attenders rated their children to have a significantly more severe illness than those who attended. These results suggest that attendance is primarily determined by social and logistical factors as well as appointment details, rather than illness severity. PMID:8660073

  11. 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

  12. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID:27249687

  13. 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…

  14. Clinical Instructors' Perceptions of the Importance of Affective Behaviors in Undergraduate Athletic Training Clinical Education

    ERIC Educational Resources Information Center

    Mokris, Rebecca L.

    2012-01-01

    The affective domain represents a set of learning objectives that are difficult to assess and instruct. Affective behaviors consist of different attributes such as interpersonal relationships, professionalism, trust, empathy, and integrity to name a few. This study surveyed athletic training clinical instructors' perception of the importance…

  15. HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand

    PubMed Central

    Sukasem, Chonlaphat; Jantararoungtong, Thawinee; Kuntawong, Parnrat; Puangpetch, Apichaya; Koomdee, Napatrupron; Satapornpong, Patompong; Supapsophon, Patcharin; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha

    2016-01-01

    Background: The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B*58:01 in a Thai population. Methods: This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system. Results: Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for HLA-B*58:01, compared to only 4.0% in allopurinol-tolerant patients (p < 0.001). Odds ratio (OR) for the association of HLA-B*58:01 with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8–6475.0). The HLA-B*58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5–11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6–8958.9, p < 0.001). Additionally, OR of HLA-B*58:01 was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9–1497.0, p < 0.001). Conclusion: In this study we confirmed the association between HLAB*58:01 and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between HLA-B*58:01 and allopurinol-induced DRESS and MPE in this population. Therefore, HLA-B*58:01 can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for HLA-B*58:01 alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients. Summary Regardless of

  16. Obstructive sleep apnea affects the clinical outcomes of patients undergoing percutaneous coronary intervention

    PubMed Central

    Zhang, Jun-jie; Gao, Xiao-fei; Ge, Zhen; Jiang, Xiao-Min; Xiao, Ping-xi; Tian, Nai-liang; Kan, Jing; Lee, Chi-Hang; Chen, Shao-Liang

    2016-01-01

    Background There is a paucity of evidence regarding the association between obstructive sleep apnea (OSA) and patients undergoing percutaneous coronary intervention (PCI) for coronary artery disease. We sought to investigate whether OSA affects the clinical outcomes of patients undergoing PCI. Patients and methods All enrolled individuals treated with PCI were evaluated for OSA by polysomnography. The primary end point was defined as major adverse cardiac events (MACEs) at 2 years, including cardiac death, myocardial infarction (MI), and/or target vessel revascularization. Results A total of 340 consecutive patients undergoing PCI were assigned to the OSA (n=152, apnea–hypopnea index ≥15) and non-OSA (n=188, apnea–hypopnea index <15) groups. The incidence of OSA in patients with coronary artery disease undergoing PCI was 44.7%. Patients in the OSA group had more three-vessel disease (34.9%), increased number of total implanted stents (3.3±2.0), and longer total stent length (83.8±53.1 mm) when compared to the non-OSA group (23.4%, P=0.020; 2.8±1.9, P=0.007; 68.7±48.4, P=0.010). After a median follow-up of 2 years, the incidence of MACEs was significantly higher in patients with OSA (25.0% vs 16.0%, P=0.038), mainly driven by the increased periprocedural MI (19.2% vs 11.2%, P=0.038) in the OSA group. By Cox regression multivariable analysis, the independent predictor of MACEs was OSA (hazard ratio: 1.962, 95% confidence interval: 1.036–3.717, P=0.039). Conclusion There was a high prevalence of moderate-to-severe OSA in patients undergoing PCI, and OSA was associated with significantly increased MACE rate, mainly due to the increase in periprocedural MI rate. PMID:27284240

  17. Genetic and Clinical Factors Affecting Plasma Clozapine Concentration

    PubMed Central

    Edman, Gunnar; Bertilsson, Leif; Hukic, Dzana Sudic; Lavebratt, Catharina; Eriksson, Sven V.; Ösby, Urban

    2015-01-01

    Objective: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. Method: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. Results: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100–2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10–0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. Conclusions: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine. PMID:26137357

  18. 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. PMID:26948519

  19. 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. PMID:27368043

  20. Genetically-induced Estrogen Receptor Alpha mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

    PubMed Central

    Heath, John; Abdelmageed, Yazeed; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Paulose, Tessie; Hernandez-Ochoa, Isabel; Gupta, Rupesh; Flaws, Jodi A.; Goyal, Hari O.

    2011-01-01

    Previously, we reported that estrogen receptor alpha mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, the genetically-induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles. PMID:20930192

  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 Central

    Ichikura, Kanako; Takeuchi, Takashi

    2016-01-01

    Objectives 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. Methods 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. Results 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). Conclusion 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. PMID:27560966

  2. 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

  3. The AFFORD Clinical Decision Aid To Identify Emergency Department Patients With Atrial Fibrillation At Low Risk For 30-Day Adverse Events

    PubMed Central

    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

    2015-01-01

    There is wide variation in the management of emergency department (ED) patients with atrial fibrillation (AF). 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 ED patients presenting with symptomatic AF. Candidate predictors were based on ED data available in the first two hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We utilized 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, prior percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms); ED data (2 hour 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% CI, 0.65, 0.76). In conclusion, among ED patients with AF, AFFORD 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. PMID:25633190

  4. High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.

    PubMed

    Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A

    2016-07-01

    Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects. PMID:27262536

  5. 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. PMID:24452733

  6. Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

    PubMed

    Maciukiewicz, Malgorzata; Pawlak, Joanna; Kapelski, Pawel; Łabędzka, Magdalena; Skibinska, Maria; Zaremba, Dorota; Leszczynska-Rodziewicz, Anna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2016-09-01

    Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder. PMID:26646576

  7. Affective dysregulation and reality distortion: a 10-year prospective study of their association and clinical relevance.

    PubMed

    van Rossum, Inge; Dominguez, Maria-de-Gracia; Lieb, Roselind; Wittchen, Hans-Ulrich; van Os, Jim

    2011-05-01

    Evidence from clinical patient populations indicates that affective dysregulation is strongly associated with reality distortion, suggesting that a process of misassignment of emotional salience may underlie this connection. To examine this in more detail without clinical confounds, affective regulation-reality distortion relationships, and their clinical relevance, were examined in a German prospective cohort community study. A cohort of 2524 adolescents and young adults aged 14-24 years at baseline was examined by experienced psychologists. Presence of psychotic experiences and (hypo)manic and depressive symptoms was assessed at 2 time points (3.5 and up to 10 years after baseline) using the Munich-Composite International Diagnostic Interview. Associations were tested between level of affective dysregulation on the one hand and incidence of psychotic experiences, persistence of these experiences, and psychotic Impairment on the other. Most psychotic experiences occurred in a context of affective dysregulation, and bidirectional dose-response was apparent with greater level of both affective dysregulation and psychotic experiences. Persistence of psychotic experiences was progressively more likely with greater level of (hypo)manic symptoms (odds ratio [OR] trend=1.51, P<.001) and depressive symptoms (OR trend=1.15, P=.012). Similarly, psychotic experiences of clinical relevance were progressively more likely to occur with greater level of affective dysregulation (depressive symptoms: OR trend=1.28, P=.002; (hypo)manic symptoms: OR trend=1.37, P=.036). Correlated genetic liabilities underlying affective and nonaffective psychotic syndromes may be expressed as correlated dimensions in the general population. Also, affective dysregulation may contribute causally to the persistence and clinical relevance of reality distortion, possibly by facilitating a mechanism of aberrant salience attribution. PMID:19793794

  8. The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

    PubMed

    Chai, Damin; Tao, Yisheng; Bao, Zhengqi; Yang, Li; Feng, Zhenzhong; Ma, Li; Liang, Limei; Zhou, Xinwen

    2013-01-01

    Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures. PMID:23924960

  9. The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.

    PubMed

    Feng, Lei; Dharmarajan, Venkatasubramanian; Serrao, Erik; Hoyte, Ashley; Larue, Ross C; Slaughter, Alison; Sharma, Amit; Plumb, Matthew R; Kessl, Jacques J; Fuchs, James R; Bushman, Frederic D; Engelman, Alan N; Griffin, Patrick R; Kvaratskhelia, Mamuka

    2016-05-20

    Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit a reduced EC50 for inhibiting HIV-1 integration in target cells. To better understand the reduced antiviral activity of ALLINIs during the early stage of HIV-1 replication, we investigated the competitive interplay between a potent representative ALLINI, BI/D, and LEDGF/p75 with HIV-1 integrase. While the principal binding sites of BI/D and LEDGF/p75 overlap at the integrase catalytic core domain dimer interface, we show that the inhibitor and the cellular cofactor induce markedly different multimerization patterns of full-length integrase. LEDGF/p75 stabilizes an integrase tetramer through the additional interactions with the integrase N-terminal domain, whereas BI/D induces protein-protein interactions in C-terminal segments that lead to aberrant, higher-order integrase multimerization. We demonstrate that LEDGF/p75 binds HIV-1 integrase with significantly higher affinity than BI/D and that the cellular protein is able to reverse the inhibitor induced aberrant, higher-order integrase multimerization in a dose-dependent manner in vitro. Consistent with these observations, alterations of the cellular levels of LEDGF/p75 markedly affected BI/D EC50 values during the early steps of HIV-1 replication. Furthermore, genome-wide sequencing of HIV-1 integration sites in infected cells demonstrate that LEDGF/p75-dependent integration site selection is adversely affected by BI/D treatment. Taken together, our studies elucidate structural and mechanistic details of the interplay between LEDGF/p75 and BI/D during the early stage of HIV-1 replication. PMID:26910179

  10. Clinical experience with nanoparticle albumin-bound paclitaxel, a novel taxane anticancer agent, and management of adverse events in females with breast cancer

    PubMed Central

    TAKASHIMA, SEIKI; KIYOTO, SACHIKO; TAKAHASHI, MINA; HARA, FUMIKATA; AOGI, KENJIRO; OHSUMI, SHOZO; MUKAI, RYOKO; FUJITA, YORIKO

    2015-01-01

    Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is currently approved in Japan for treatment of breast cancer. However, apart from phase I clinical trials, data regarding Japanese patients are scant. In the present study, the efficacy and safety of nab-paclitaxel therapy were retrospectively analyzed in 22 patients with advanced or metastatic breast cancer who were treated at the National Hospital Organization Shikoku Cancer Center between November 2010 and June 2012. The nab-paclitaxel was administered once every three weeks. The median age of the patients was 59 years. The tumors were estrogen-receptor positive and/or progesterone-receptor positive in 63.6% patients. None of the patients had HER2-positive breast cancer. The median number of treatment cycles was six (range, two to 12). Six patients exhibited a partial response; the response rate was 27.3% and the clinical benefit rate was 31.8%. The response rate and clinical benefit rate were higher in patients who received nab-paclitaxel as first- or second-line treatment. The median time to treatment failure was 127 days (range, 27–257). Major adverse events were peripheral neuropathy (59%; Grade 3, 9%), myalgia (59%), rash (45%), and nausea and vomiting (50%). The results suggest that nab-paclitaxel is a well-tolerated and clinically useful anticancer preparation. PMID:25789050

  11. Adverse Event Recording and Reporting in Clinical Trials Comparing Lumbar Disk Replacement with Lumbar Fusion: A Systematic Review

    PubMed Central

    Hiratzka, Jayme; Rastegar, Farbod; Contag, Alec G.; Norvell, Daniel C.; Anderson, Paul A.; Hart, Robert A.

    2015-01-01

    Study Design Systematic review. Objectives (1) To compare the quality of adverse event (AE) methodology and reporting among randomized trials comparing lumbar fusion with lumbar total disk replacement (TDR) using established AE reporting systems; (2) to compare the AEs and reoperations of lumbar spinal fusion with those from lumbar TDR; (3) to make recommendations on how to report AEs in randomized controlled trials (RCTs) so that surgeons and patients have more-detailed and comprehensive information when making treatment decisions. Methods A systematic search of PubMed, the Cochrane collaboration database, and the National Guideline Clearinghouse through May 2015 was conducted. Randomized controlled trials with at least 2 years of follow-up comparing lumbar artificial disk replacement with lumbar fusion were included. Patients were required to have axial or mechanical low back pain of ≥3 months' duration due to degenerative joint disease defined as degenerative disk disease, facet joint disease, or spondylosis. Outcomes included the quality of AE acquisition methodology and results reporting, and AEs were defined as those secondary to the procedure and reoperations. Individual and pooled relative risks and their 95% confidence intervals comparing lumbar TDR with fusion were calculated. Results RCTs demonstrated a generally poor description of methods for assessing AEs. There was a consistent lack of clear definition or grading for these events. Furthermore, there was a high degree of variation in reporting of surgery-related AEs. Most studies lacked adequate reporting of the timing of AEs, and there were no clear distinctions between acute or chronic AEs. Meta-analysis of the pooled data demonstrated a twofold increased risk of AEs in patients having lumbar fusion compared with patients having lumbar TDR at 2-year follow-up, and this relative risk was maintained at 5 years. Furthermore, the pooled data demonstrated a 1.7 times greater relative risk of

  12. Adverse Event Recording and Reporting in Clinical Trials Comparing Lumbar Disk Replacement with Lumbar Fusion: A Systematic Review.

    PubMed

    Hiratzka, Jayme; Rastegar, Farbod; Contag, Alec G; Norvell, Daniel C; Anderson, Paul A; Hart, Robert A

    2015-12-01

    Study Design Systematic review. Objectives (1) To compare the quality of adverse event (AE) methodology and reporting among randomized trials comparing lumbar fusion with lumbar total disk replacement (TDR) using established AE reporting systems; (2) to compare the AEs and reoperations of lumbar spinal fusion with those from lumbar TDR; (3) to make recommendations on how to report AEs in randomized controlled trials (RCTs) so that surgeons and patients have more-detailed and comprehensive information when making treatment decisions. Methods A systematic search of PubMed, the Cochrane collaboration database, and the National Guideline Clearinghouse through May 2015 was conducted. Randomized controlled trials with at least 2 years of follow-up comparing lumbar artificial disk replacement with lumbar fusion were included. Patients were required to have axial or mechanical low back pain of ≥3 months' duration due to degenerative joint disease defined as degenerative disk disease, facet joint disease, or spondylosis. Outcomes included the quality of AE acquisition methodology and results reporting, and AEs were defined as those secondary to the procedure and reoperations. Individual and pooled relative risks and their 95% confidence intervals comparing lumbar TDR with fusion were calculated. Results RCTs demonstrated a generally poor description of methods for assessing AEs. There was a consistent lack of clear definition or grading for these events. Furthermore, there was a high degree of variation in reporting of surgery-related AEs. Most studies lacked adequate reporting of the timing of AEs, and there were no clear distinctions between acute or chronic AEs. Meta-analysis of the pooled data demonstrated a twofold increased risk of AEs in patients having lumbar fusion compared with patients having lumbar TDR at 2-year follow-up, and this relative risk was maintained at 5 years. Furthermore, the pooled data demonstrated a 1.7 times greater relative risk of

  13. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

    PubMed

    Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

    2014-09-01

    Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient. PMID:24760409

  14. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence of the adverse effects of industrially-produced trans fatty acids (iTFA) on risk of cardiovascular disease is consistent and well documented in the scientific literature; however, the cardiovascular effects of naturally-occurring TFA synthesized in ruminant animals (rTFA), such as vaccenic ...

  15. Application of a human factors classification framework for patient safety to identify precursor and contributing factors to adverse clinical incidents in hospital.

    PubMed

    Mitchell, Rebecca J; Williamson, Ann; Molesworth, Brett

    2016-01-01

    This study aimed to identify temporal precursor and associated contributing factors for adverse clinical incidents in a hospital setting using the Human Factors Classification Framework (HFCF) for patient safety. A random sample of 498 clinical incidents were reviewed. The framework identified key precursor events (PE), contributing factors (CF) and the prime causes of incidents. Descriptive statistics and correspondence analysis were used to examine incident characteristics. Staff action was the most common type of PE identified. Correspondence analysis for all PEs that involved staff action by error type showed that rule-based errors were strongly related to performing medical or monitoring tasks or the administration of medication. Skill-based errors were strongly related to misdiagnoses. Factors relating to the organisation (66.9%) or the patient (53.2%) were the most commonly identified CFs. The HFCF for patient safety was able to identify patterns of causation for the clinical incidents, highlighting the need for targeted preventive approaches, based on an understanding of how and why incidents occur. PMID:26360210

  16. Cognitive and affective components of Theory of Mind in preschoolers with oppositional defiance disorder: Clinical evidence.

    PubMed

    de la Osa, Nuria; Granero, Roser; Domenech, Josep Maria; Shamay-Tsoory, Simone; Ezpeleta, Lourdes

    2016-07-30

    The goal of the study was to examine the affective-cognitive components of Theory of Mind (ToM), in a community sample of 538 preschoolers, and more specifically in a subsample of 40 children diagnosed with ODD. The relationship between affective and cognitive ToM and some ODD clinical characteristics was examined. Children were assessed with structured diagnostic interviews and dimensional measures of psychopathology, impairment and unemotional traits. A measure based on eye-gaze was used to assess ToM. Mixed analysis of variance compared the mean cognitive versus affective scale scores and the between-subjects factor ODD. The association between ToM-scores and clinical measures was assessed through correlation models. Execution and reaction time to emotional and cognitive components of ToM tasks are different at age 5 in normally developing children. Oppositional Defiant children had slower response time when performing the affective mentalizing condition than children without the disorder. The correlation matrix between ToM-scores and clinical measures showed specific associations depending on the impaired ToM aspect and the psychological domain. Results may have clinical implications for the prevention and management of ODD. PMID:27173657

  17. The Affective Reactivity Index: A Concise Irritability Scale for Clinical and Research Settings

    ERIC Educational Resources Information Center

    Stringaris, Argyris; Goodman, Robert; Ferdinando, Sumudu; Razdan, Varun; Muhrer, Eli; Leibenluft, Ellen; Brotman, Melissa A.

    2012-01-01

    Background: Irritable mood has recently become a matter of intense scientific interest. Here, we present data from two samples, one from the United States and the other from the United Kingdom, demonstrating the clinical and research utility of the parent- and self-report forms of the Affective Reactivity Index (ARI), a concise dimensional measure…

  18. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  19. Evaluation of clinical bradycardiac effect and respiratory adverse effect of β-blocking agents in coronary computed tomography angiography based on theoretical analysis.

    PubMed

    Fujito, Kaori; Takayanagi, Risa; Kimura, Koji; Yokoyama, Haruko; Yamada, Yasuhiko

    2016-04-01

    β-blocking agents are used for patients with tachycardia to improve the image quality of coronary computed tomography angiography (CCTA). In this study, we analyzed the clinical bradycardiac effects and the adverse respiratory effects of five β-blocking agents (landiolol, esmolol, propranolol, metoprolol and atenolol) used for CCTA. The changes of the occupancy binding to β1 or β2 receptor of these drugs were calculated based on the receptor occupancy theory. Thereafter, we predicted both the rate of heart rate decline (▲HR) as a clinical effect and the rate of decrease in forced expiratory volume in 1 s (▲FEV1) as an adverse effect, by using the ternary complex model. The results showed that the drugs with ▲HR greater than 10 %, necessary for CCTA, were as follows: landiolol at 13.5 %, propranolol at 11.0 %, and atenolol at 22.6 %. The ▲HR values at the end of CCTA for those three drugs were 0.3, 6.7, and 22.9 %, respectively. It is desirable for the bradycardiac effect to disappear at the end of CCTA. Therefore, landiolol is thought to be a preferable drug. On the other hand, ▲FEV1 at start and end of CCTA for those three drugs was 0.04-2.5, 34.9-40.3, and 6.0-6.1 %, respectively. Our results suggested that landiolol has the most appropriate effect and safety for patients with tachycardia who are undergoing a CCTA procedure. PMID:25510848

  20. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  1. High-Flow Nasal Cannula Oxygen Therapy in Adults: Physiological Benefits, Indication, Clinical Benefits, and Adverse Effects.

    PubMed

    Nishimura, Masaji

    2016-04-01

    High-flow nasal cannula (HFNC) oxygen therapy is carried out using an air/oxygen blender, active humidifier, single heated tube, and nasal cannula. Able to deliver adequately heated and humidified medical gas at flows up to 60 L/min, it is considered to have a number of physiological advantages compared with other standard oxygen therapies, including reduced anatomical dead space, PEEP, constant FIO2 , and good humidification. Although few large randomized clinical trials have been performed, HFNC has been gaining attention as an alternative respiratory support for critically ill patients. Published data are mostly available for neonates. For critically ill adults, however, evidence is uneven because the reports cover various subjects with diverse underlying conditions, such as hypoxemic respiratory failure, exacerbation of COPD, postextubation, preintubation oxygenation, sleep apnea, acute heart failure, and conditions entailing do-not-intubate orders. Even so, across the diversity, many published reports suggest that HFNC decreases breathing frequency and work of breathing and reduces the need for respiratory support escalation. Some important issues remain to be resolved, such as definitive indications for HFNC and criteria for timing the starting and stopping of HFNC and for escalating treatment. Despite these issues, HFNC has emerged as an innovative and effective modality for early treatment of adults with respiratory failure with diverse underlying diseases. PMID:27016353

  2. 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

  3. ["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

  4. ["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

  5. 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…

  6. High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer

    PubMed Central

    van den Broek, Evert; Dijkstra, Maurits J. J.; Krijgsman, Oscar; Sie, Daoud; Haan, Josien C.; Traets, Joleen J. H.; van de Wiel, Mark A.; Nagtegaal, Iris D.; Punt, Cornelis J. A.; Carvalho, Beatriz; Ylstra, Bauke; Abeln, Sanne; Meijer, Gerrit A.; Fijneman, Remond J. A.

    2015-01-01

    Background Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA) and structural variants (SVs). Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC) and to determine the clinical relevance of recurrent breakpoint genes. Methods Primary CRC samples of patients with metastatic disease from CAIRO and CAIRO2 clinical trials were previously characterized by array-comparative genomic hybridization. These data were now used to determine the prevalence of CNA-associated chromosomal breaks within genes across 352 CRC samples. In addition, mutation status of the commonly affected APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS genes was determined for 204 CRC samples by targeted massive parallel sequencing. Clinical relevance was assessed upon stratification of patients based on gene mutations and gene breakpoints that were observed in >3% of CRC cases. Results In total, 748 genes were identified that were recurrently affected by chromosomal breaks (FDR <0.1). MACROD2 was affected in 41% of CRC samples and another 169 genes showed breakpoints in >3% of cases, indicating that prevalence of gene breakpoints is comparable to the prevalence of well-known gene point mutations. Patient stratification based on gene breakpoints and point mutations revealed one CRC subtype with very poor prognosis. Conclusions We conclude that CNA-associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC. PMID:26375816

  7. 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

  8. Optical coherence tomography derived cut-off value of uncovered stent struts to predict adverse clinical outcomes after drug-eluting stent implantation.

    PubMed

    Won, Hoyoun; Shin, Dong-Ho; Kim, Byeong-Keuk; Mintz, Gary S; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2013-08-01

    Although the presence of uncovered struts may be associated with occurrence of stent thrombosis, the impact of uncovered struts detected routinely by optical coherence tomography (OCT) on subsequent long-term clinical outcomes remains unclear. The objective of this study was to determine the cut-off value of uncovered struts that predicted adverse clinical outcomes after drug eluting stent (DES) implantation. Major safety events (MSEs, a composite occurrence of cardiovascular death, myocardial infarction, and stent thrombosis) were evaluated in 489 DES-treated patients (535 lesions) during the median 851 days after follow-up OCT. MSEs occurred in six patients (four definite stent thrombosis and two sudden cardiac death). The best cut-off value of percentage of uncovered struts for predicting MSE was 5.9 % using the maximal χ(2) method: area under the receiver-operating characteristic curve = 0.779, 95 % confidence interval (CI) = 0.648-0.910, p = 0.019, a sensitivity of 83.3 % and a specificity of 70.3 %. Independent predictors for MSE were post-intervention minimal lumen diameter (odds ratio 0.019, 95 % CI = 0.001-0.513, p = 0.018) and percentage of uncovered struts ≥5.9 % (odds ratio 19.781, 95 % CI = 2.071-188.968, p = 0.010). A greater percentage of uncovered struts (the cut-off value of ≥5.9 % uncovered struts) might be significantly associated with occurrence of MSE after DES implantation. PMID:23615849

  9. Assessing the Performance Characteristics of Signals Used by a Clinical Event Monitor to Detect Adverse Drug Reactions in the Nursing Home

    PubMed Central

    Handler, Steven M.; Hanlon, Joseph T.; Perera, Subashan; Saul, Melissa I.; Fridsma, Douglas B.; Visweswaran, Shyam; Studenski, Stephanie A.; Roumani, Yazan F.; Castle, Nicholas G.; Nace, David A.; Becich, Michael J.

    2008-01-01

    Adverse drug reactions (ADRs) are a common cause of morbidity and mortality in the nursing home (NH) setting. Traditional non-automated mechanisms for ADR detection are time-consuming, costly, and fail to detect the majority of ADRs. We describe the implementation and pharmacist evaluation of a clinical event monitor using signals previously developed by our research team to detect potential ADRs in the NH. The overall positive predictive value (PPV) for all signals combined was 81% (54/67), with individual signal PPVs ranging from 0-100%. The PPVs were 53% (10/19) for the antidote signals category and 96% (44/46) for the laboratory/medication combination signals category. The majority 75% (12/16) of the preventable ADRs were laboratory/medication combination signals. The results suggest that ADRs can be detected in the NH setting with a high degree of accuracy using a clinical event monitor that employs a set of signals derived by expert consensus. PMID:18998853

  10. Endoscopic and Clinical Factors Affecting the Prognosis of Colorectal Endoscopic Submucosal Dissection-Related Perforation

    PubMed Central

    Kang, Dong-Uk; Choi, Yunsik; Lee, Ho-Su; Lee, Hyo Jeong; Park, Sang Hyoung; Yang, Dong-Hoon; Yoon, Soon Man; Kim, Kyung-Jo; Ye, Byong Duk; Myung, Seung-Jae; Yang, Suk-Kyun; Kim, Jin-Ho; Byeon, Jeong-Sik

    2016-01-01

    Background/Aims Although colorectal endoscopic submucosal dissection (ESD)-related perforation is not uncommon, the factors affecting clinical outcomes after perforation have not been investigated. This study was designed to investigate the factors influencing the clinical course of ESD-related colon perforation. Methods Forty-three patients with colorectal ESD-related perforation were evaluated. The perforations were classified as endoscopic or radiologic perforations. The patients’ medical records and endoscopic pictures were analyzed. Results The clinical outcomes were assessed by the duration of nil per os, intravenous antibiotics administration, and hospital stays, which were 2.7±1.5, 4.9±2.3, and 5.1±2.3 days, respectively. Multivariate analyses revealed that a larger tumor size, ESD failure, specific endoscopists, and abdominal pain were independently related to a poorer outcome. The time between perforation and clipping was 15.8±25.4 minutes in the endoscopic perforation group. The multivariate analysis of this group indicated that delayed clipping, specific endoscopists, and abdominal pain were independently associated with poorer outcomes. Conclusions Tumor size, ESD failure, abdominal pain, and the endoscopist were factors that affected the clinical outcomes of patients with colorectal ESD-related perforation. The time between the perforation and clipping was an additional factor influencing the clinical course of endoscopic perforation. Decreasing this time period may improve outcomes. PMID:26780090

  11. Clinical use of coping in affective disorder, a critical review of the literature

    PubMed Central

    2005-01-01

    Background The relationship between life stressors, coping and affective disorder is interesting when predicting onset of a affective disorder and relapse of mood episodes. Methods A litteratur review of cross-sectional and longitudinal studies concerning coping and affective disorder in adults including a Medline and Embase search was conducted. Results 11 cross-sectional studies and 17 longitudinal studies concerning affective disorder and coping were found, among these, two studies include patients with bipolar disorder exclusively. Only four studies elucidate whether emotion-oriented and/or avoidance coping styles are associated with a higher risk of developing affective disorder, so this hypothesis remains unclear. Most studies shows that emotion-oriented and avoidance coping strategies are associated with relapse of depressive episodes. Conversely, problem-focused and task-oriented coping seem to be associated with a good outcome. Conclusion There is a gap between coping theory and clinical use of coping and the clinical relevance of coping is, though promising, still unclear. In future research it is recommended to concentrate on development of a semi-structured interview combining coping style, life events and personality traits. PMID:16212656

  12. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome

    PubMed Central

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

    2014-01-01

    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting. PMID:24976697

  13. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

    PubMed

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

    2014-06-28

    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting. PMID:24976697

  14. High d(+)-fructose diet adversely affects testicular weight gain in weaning rats─protection by moderate d(+)-glucose diet.

    PubMed

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2013-01-01

    The use of high D(+)-fructose corn syrup has increased over the past several decades in the developed countries, while overweight and obesity rates and the related diseases have risen dramatically. However, we found that feeding a high D(+)-fructose diet (80% D(+)-fructose as part of the diet) to weaning rats for 21 days led to reduced food intake (50% less, P < 0.0001) and thus delayed the weight gains in the body (40% less, P < 0.0001) and testes (40% less, P < 0.0001) compared to the no D(+)-fructose diet. We also challenged a minimum requirement of dietary D(+)-glucose for preventing the adverse effects of D(+)-fructose, such as lower food intake and reduction of body weight and testicular weight; the minimum requirement of D(+)-glucose was ≈23% of the diet. This glucose amount may be the minimum requirement of exogenous glucose for reducing weight gain. PMID:23935370

  15. Confirmation of in vitro and clinical safety assessment of behentrimonium chloride-containing leave-on body lotions using post-marketing adverse event data.

    PubMed

    Cameron, D M; Donahue, D A; Costin, G-E; Kaufman, L E; Avalos, J; Downey, M E; Billhimer, W L; Gilpin, S; Wilt, N; Simion, F A

    2013-12-01

    Behentrimonium chloride (BTC) is a straight-chain alkyltrimonium chloride compound commonly used as an antistatic, hair conditioning, emulsifier, or preservative agent in personal care products. Although the European Union recently restricted the use of alkyltrimonium chlorides and bromides as preservatives to ≤0.1%, these compounds have been safely used for many years at ≤5% in hundreds of cosmetic products for other uses than as a preservative. In vitro, clinical, and controlled consumer usage tests in barrier-impaired individuals were conducted to determine if whole body, leave-on skin care products containing 1-5% BTC cause dermal irritation or any other skin reaction with use. BTC-containing formulations were predicted to be non-irritants by the EpiDerm® skin irritation test and the bovine corneal opacity and permeability (BCOP)/chorioallantoic membrane vascular assay (CAMVA) ocular irritation test battery. No evidence of allergic contact dermatitis or cumulative dermal irritation was noted under the exaggerated conditions of human occlusive patch tests. No clinically assessed or self-reported adverse reactions were noted in adults or children with atopic, eczematous, and/or xerotic skin during two-week and four-week monitored home usage studies. These results were confirmed by post-marketing data for five body lotions, which showed only 0.69 undesirable effects (mostly skin irritation) reported per million shipped consumer units during 2006-2011; a value consistent with a non-irritating body lotion. No serious undesirable effects were reported during in-market use of the products. Therefore, if formulated in appropriate conditions at 1-5%, BTC will not cause dermal irritation or delayed contact sensitization when used in a whole-body, leave-on product. PMID:24064305

  16. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.

    PubMed

    Zhao, Yan; Li, Hailiang; Bai, Wei; Liu, Jueshi; Lv, Weifu; Sahu, Sonia; Guan, Sheng; Qin, Xiao; Wang, Wenhui; Ren, Weixin; Mu, Wei; Guo, Weidong; Gu, Shanzhi; Ma, Yilong; Yin, Zhanxin; Guo, Wengang; Wang, Wenjun; Wang, Yongji; Duran, Rafael; Fan, Daiming; Zhang, Zhuoli; Han, Guohong

    2016-08-15

    The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials. PMID:27038145

  17. Medication Monitoring in a Nurse-Led Respiratory Outpatient Clinic: Pragmatic Randomised Trial of the West Wales Adverse Drug Reaction Profile

    PubMed Central

    Gabe, Marie E.; Murphy, Fiona; Davies, Gwyneth A.; Russell, Ian T.; Jordan, Susan

    2014-01-01

    Objective To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine. Design Single-site parallel-arm pragmatic trial using stratified randomisation. Setting Nurse-led respiratory outpatient clinic in general hospital in South Wales. Participants 54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists. Intervention Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care (‘intervention arm’ with 26 participants); or usual care alone (‘control arm’ with 28 participants). Main Outcome Measures Problems reported and actions taken. Results We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13–26], while that in the control arm was −1 [−3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]–[4] while that in the control arm was 0 [−1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001]. Conclusion When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management. Trial Registration Controlled-trials.com ISRCTN10386209 PMID:24798210

  18. Correlation Between the Clinical Parameters and Tissue Phenotype in Patients Affected by Deep-Infiltrating Endometriosis.

    PubMed

    Vinci, Giovanna; Arkwright, Sylviane; Audebourg, Anne; Radenen, Brigitte; Chapron, Charles; Borghese, Bruno; Dousset, Bertrand; Mehats, Celine; Vaiman, Daniel; Vacher-Lavenu, Marie-Cécile; Gogusev, Jean

    2016-09-01

    The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care. PMID:26994067

  19. Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals.

    PubMed

    Müller, K E; Bernadina, W E; Kalsbeek, H C; Hoek, A; Rutten, V P; Wentink, G H

    1994-03-01

    The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described. Affected animals were presented with a history of poor thriving and recurrent bacterial infections. Five of these animals had to be killed because of severe respiratory disease shortly after admittance. Three affected animals survived calfhood only as a result of frequent antibacterial treatments. At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically. Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis). A leukocytosis based on a mature neutrophilia, which persisted during infection-free periods, was observed in all animals. Granulocytes were substantially deficient of beta 2-integrin expression on their membranes. Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID). The serum total protein content increased with time and was associated with elevated gamma-globulin levels. We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system. PMID:8009815

  20. Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals.

    PubMed

    Müller, K E; Bernadina, W E; Kalsbeek, H C; Hoek, A; Rutten, V P; Wentink, G H

    1994-07-01

    The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described. Affected animals were presented with a history of poor thriving and recurrent bacterial infections. Five of these animals had to be killed because of severe respiratory disease shortly after admittance. Three affected animals survived calfhood only as a result of frequent antibacterial treatments. At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically. Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis). A leukocytosis based on a mature neutrophilia, which persisted during infection-free periods, was observed in all animals. Granulocytes were substantially deficient of beta 2-integrin expression on their membranes. Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID). The serum total protein content increased with time and was associated with elevated gamma-globulin levels. We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system. PMID:7985357

  1. Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

    PubMed Central

    2009-01-01

    Background Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. Patients and methods 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple

  2. Factors affecting the clinical development of cytochrome p450 3A substrates.

    PubMed

    Gibbs, Megan A; Hosea, Natilie A

    2003-01-01

    The objective of this review is to evaluate the risks associated with the discovery and development of cytochrome p450 (CYP) 3A substrates. CYP3A is the most abundant p450 enzyme in human liver and is highly expressed in the intestinal tract. The enzyme contributes substantially to metabolism of approximately 50% of currently marketed drugs that undergo oxidative metabolism. As a result, drug-drug interactions involving inhibitors of CYP3A-mediated metabolism can be of great clinical consequence. It is the position of the authors that, because of the factors responsible for the broad substrate specificity of CYP3A, discovery and development of compounds across a large and broad portfolio that are completely devoid of CYP3A metabolism is not feasible. Thus, it is important that scientifically valid approaches to the discovery and development of compounds metabolised by CYP3A be realised. The clinical relevance of CYP3A metabolism is dependent on a multitude of factors that include the degree of intestinal and hepatic CYP3A-mediated first-pass extraction, the therapeutic index of the compound and the adverse event associated with inhibition of CYP3A metabolism. Thus, a better understanding of the disposition of a CYP3A-metabolised compound relative to the projected or observed therapeutic index (or safety margin) can provide ample evidence to support the continued development of a CYP3A substrate. This document will highlight current practices as well as the benefits and risks associated with those practices. PMID:12908853

  3. Migration, neighborhoods, and networks: approaches to understanding how urban environmental conditions affect syndemic adverse health outcomes among gay, bisexual and other men who have sex with men.

    PubMed

    Egan, James E; Frye, Victoria; Kurtz, Steven P; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A

    2011-04-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  4. Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA.

    PubMed

    Roberts, Ainslie L K; Fletcher, Janice M; Moore, Lynette; Byers, Sharon

    2010-01-01

    MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studies in MPS IIIA mice have shown that rhodamine B substrate deprivation therapy (SDT) (also termed substrate reduction therapy/SRT) inhibits GAG biosynthesis and, improves both somatic and CNS disease pathology. Acute overexposure to high doses of rhodamine B results in liver toxicity and is detrimental to reproductive ability. However, the long-term effects of decreasing GAG synthesis, at the low dose sufficient to alter neurological function are unknown. A trans-generational study was therefore initiated to evaluate the continuous exposure of rhodamine B treatment in MPS IIIA mice over 4 generations, including treatment during pregnancy. No alterations in litter size, liver histology or liver function were observed. Overall, there are no long-term issues with the administration of rhodamine B at the low dose tested and no adverse effects were noted during pregnancy in mice. PMID:20650670

  5. Rock Glacier Outflows May Adversely Affect Lakes: Lessons from the Past and Present of Two Neighboring Water Bodies in a Crystalline-Rock Watershed

    PubMed Central

    2014-01-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake’s history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  6. Rock glacier outflows may adversely affect lakes: lessons from the past and present of two neighboring water bodies in a crystalline-rock watershed.

    PubMed

    Ilyashuk, Boris P; Ilyashuk, Elena A; Psenner, Roland; Tessadri, Richard; Koinig, Karin A

    2014-06-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake's history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  7. Plasmid load adversely affects growth and gluconic acid secretion ability of mineral phosphate-solubilizing rhizospheric bacterium Enterobacter asburiae PSI3 under P limited conditions.

    PubMed

    Sharma, Vikas; Archana, G; Naresh Kumar, G

    2011-01-20

    Effect of the metabolic load caused by the presence of plasmids on mineral phosphate-solubilizing (MPS) Enterobacter asburiae PSI3, was monitored with four plasmid cloning vectors and one native plasmid, varying in size, nature of the replicon, copy number and antibiotic resistance genes. Except for one plasmid, the presence of all other plasmids in E. asburiae PSI3 resulted in the loss of the MPS phenotype as reflected by the failure to bring about a drop in pH and release soluble P when grown in media containing rock phosphate (RP) as the sole P source. When 100 μM soluble P was supplemented along with RP, the adverse effects of plasmids on MPS phenotype and on growth parameters was reduced for some plasmid bearing derivatives, as monitored in terms of specific growth rates, glucose consumed, gluconic acids yields and P released. When 10 mM of soluble P as the only P source, was added to the medium all transformants showed growth and pH drop comparable with native strain. It may be concluded that different plasmids impose, to varying extents, a metabolic load in the phosphate-solubilizing bacterium E. asburiae PSI3 and results in diminishing its growth and P-solubilizing ability in P deficient conditions. PMID:20171856

  8. Migration, Neighborhoods, and Networks: Approaches to Understanding How Urban Environmental Conditions Affect Syndemic Adverse Health Outcomes Among Gay, Bisexual and Other Men Who Have Sex with Men

    PubMed Central

    Egan, James E.; Kurtz, Steven P.; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A.

    2011-01-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  9. Demographic and Clinical Findings in Pediatric Patients Affected by Organic Acidemia

    PubMed Central

    NAJAFI, Reza; HASHEMIPOUR, Mahin; MOSTOFIZADEH, Neda; GHAZAVI, Mohammadreza; NASIRI, Jafar; SHAHSANAI, Armindokht; FAMORI, Fatemeh; NAJAFI, Fatemeh; MOAFI, Mohammad

    2016-01-01

    Objective Metabolic disorders, which involve many different organs, can be ascribed to enzyme deficiency or dysfunction and manifest with a wide range of clinical symptoms. This study evaluated some of the demographic and clinical findings in pediatric patients affected by organic acidemia. Materials & Methods This cross-sectional study was part of a larger study conducted in patients with metabolic disorders during a period of 7 years from 2007 to 2014 in Isfahan Province, Iran. Our study covered a wide range of cases from newborn infants (one-week old) to adolescents (children up to the age of 17 years). This study evaluated patients’ demographic information, history of disease, developmental and educational status, clinical and general conditions. Phone and in-person interviews were used to gather information. Results Out of 5100 patients screened in this study, 392 patients were affected by one of the different metabolic disorders and 167 individuals were diagnosed as organic acidemia. Propionic acidemia/methyl malonic acidemia (PA/MMA) was the most prevalent form of this metabolic disorder. The frequency of consanguinity was 84.7% in the group of patients. The mortality rate was 18.8% in patients with organic academia. Conclusion Each of the metabolic diseases, as a separate entity, is rare; nevertheless, in aggregate they have a somewhat high overall prevalence. These diseases result in mental and developmental disorders in the absence of quick diagnosis and initiation of treatment. Furthermore, more mutations should be identified in societies affected by consanguinity. Further research should also be conducted to determine worthwhile and more-efficient screening methods as well as long term neurological prognosis. PMID:27247587

  10. Graphic Warning Labels Elicit Affective and Thoughtful Responses from Smokers: Results of a Randomized Clinical Trial

    PubMed Central

    Evans, Abigail T.; Peters, Ellen; Strasser, Andrew A.; Emery, Lydia F.; Sheerin, Kaitlin M.; Romer, Daniel

    2015-01-01

    Objective Observational research suggests that placing graphic images on cigarette warning labels can reduce smoking rates, but field studies lack experimental control. Our primary objective was to determine the psychological processes set in motion by naturalistic exposure to graphic vs. text-only warnings in a randomized clinical trial involving exposure to modified cigarette packs over a 4-week period. Theories of graphic-warning impact were tested by examining affect toward smoking, credibility of warning information, risk perceptions, quit intentions, warning label memory, and smoking risk knowledge. Methods Adults who smoked between 5 and 40 cigarettes daily (N = 293; mean age = 33.7), did not have a contra-indicated medical condition, and did not intend to quit were recruited from Philadelphia, PA and Columbus, OH. Smokers were randomly assigned to receive their own brand of cigarettes for four weeks in one of three warning conditions: text only, graphic images plus text, or graphic images with elaborated text. Results Data from 244 participants who completed the trial were analyzed in structural-equation models. The presence of graphic images (compared to text-only) caused more negative affect toward smoking, a process that indirectly influenced risk perceptions and quit intentions (e.g., image->negative affect->risk perception->quit intention). Negative affect from graphic images also enhanced warning credibility including through increased scrutiny of the warnings, a process that also indirectly affected risk perceptions and quit intentions (e.g., image->negative affect->risk scrutiny->warning credibility->risk perception->quit intention). Unexpectedly, elaborated text reduced warning credibility. Finally, graphic warnings increased warning-information recall and indirectly increased smoking-risk knowledge at the end of the trial and one month later. Conclusions In the first naturalistic clinical trial conducted, graphic warning labels are more effective

  11. Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia

    PubMed Central

    Girschick, HJ; Schneider, P; Haubitz, I; Hiort, O; Collmann, H; Beer, M; Shin, YS; Seyberth, HW

    2006-01-01

    Background Hypophosphatasia (HP) is an inborn error of bone metabolism characterized by a genetic defect in the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP). There is a lack of knowledge as to how the variability and clinical severity of the HP phenotype (especially pain and walking impairment) are related to metabolic disturbances or impairments, subsequent to the molecular defect. Methods We analyzed the changes in clinical symptoms and the prostaglandin (PG) metabolism in response to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in six children affected by childhood HP. In addition, by exposing HP fibroblasts to pyridoxal phosphate and/or calcium pyrophosphate in vitro, we analyzed whether the alterations in PG levels are sequelae related to the metabolic defect. Results Childhood HP patients, who often complain about pain in the lower limbs without evident fractures, have systemic hyperprostaglandinism. Symptomatic anti-inflammatory treatment with NSAIDs significantly improved pain-associated physical impairment. Calcium pyrophosphate, but not pyridoxal phosphate, induced cyclooxygenase-2 (COX-2) gene expression and PG production in HP and normal fibroblasts in vitro. Conclusion Clinical features of childhood HP related to pain in the lower legs may be, at least in part, sequelae related to elevated PG levels, secondary to the primary metabolic defect. Consequently, NSAID treatment does improve the clinical features of childhood HP. PMID:16803637

  12. Broad Clinical Involvement in a Family Affected by the Fragile X Premutation

    PubMed Central

    CHONCHAIYA, WEERASAK; UTARI, AGUSTINI; PEREIRA, GABRIELA MARQUES; TASSONE, FLORA; HESSL, DAVID; HAGERMAN, RANDI J.

    2009-01-01

    The mutations in the FMR1 gene have been described as a family of disorders called fragile X-associated disorders (FXD) including fragile X syndrome (FXS), fragile X-associated tremor/ ataxia syndrome (FXTAS), primary ovarian insufficiency and other problems associated with the premutation, such as hypothyroidism, hypertension, neuropathy, anxiety, depression, attention deficit hyperactivity disorders and autism spectrum disorders. The premutation is relatively common in the general population affecting 1 of 130–250 female individuals and 1 of 250–800 male individuals. Therefore, to provide appropriate treatment and genetic counseling for all of the carriers and affected individuals in a family, a detailed family history that reviews many of the disorders that are related to both the premutation and the full mutation should be carried out as exemplified in these cases. To facilitate the integration of this knowledge into clinical practice, this is the first case report that demonstrates only premutation involvement across 3 generations. PMID:19996900

  13. Broad clinical involvement in a family affected by the fragile X premutation.

    PubMed

    Chonchaiya, Weerasak; Utari, Agustini; Pereira, Gabriela Marques; Tassone, Flora; Hessl, David; Hagerman, Randi J

    2009-12-01

    The mutations in the FMR1 gene have been described as a family of disorders called fragile X-associated disorders including fragile X syndrome, fragile X-associated tremor/ataxia syndrome, primary ovarian insufficiency, and other problems associated with the premutation, such as hypothyroidism, hypertension, neuropathy, anxiety, depression, attention-deficit hyperactivity disorders, and autism spectrum disorders. The premutation is relatively common in the general population affecting 1 of 130 to 250 female individuals and 1 of 250 to 800 male individuals. Therefore, to provide appropriate treatment and genetic counseling for all of the carriers and affected individuals in a family, a detailed family history that reviews many of the disorders that are related to both the premutation and the full mutation should be carried out as exemplified in these cases. To facilitate the integration of this knowledge into clinical practice, this is the first case report that demonstrates only premutation involvement across 3 generations. PMID:19996900

  14. Signet ring cell histology is associated with unique clinical features but does not affect gastric cancer survival.

    PubMed

    Theuer, C P; Nastanski, F; Brewster, W R; Butler, J A; Anton-Culver, H

    1999-10-01

    Signet ring cell histology is found in 3 to 39 per cent of gastric cancer cases and has been reported to be a feature of poor prognosis, although this issue has not been rigorously examined. The objective of this study was to determine those demographic and clinical variables associated with signet ring cell histology and to determine the effect of signet ring cell histology on survival using multivariate analyses. We studied a historical cohort of consecutive cases of gastric cancer reported to the population-based California Cancer Registries of Orange, San Diego, and Imperial Counties from 1984 through 1994. Factors associated with signet ring cell histology were assessed using chi2 and logistic regression. Life tables were constructed to assess unadjusted survival and survival differences in patient subgroups. Multivariate survival was determined using a Cox proportional hazards model. Of 3020 patients, 464 (15%) had signet ring cell histology. Patients with signet ring cell histology were more likely to be younger than 50 years (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.5), less likely to be male (OR = 0.49; 95% CI = 0.37-0.66), and more likely to have tumors of the distal stomach (OR = 2.0; 95% CI = 1.4-3.0). Signet ring cell histology did not adversely affect unadjusted overall survival, race-stratified survival, or stage-stratified survival. Multivariate analysis indicated that patients with signet ring cell histology had an insignificant increased risk of dying (relative risk = 1.027; P>0.10) in comparison with patients without signet ring cell histology. Patients with signet ring cell histology were more likely to be young women and to have tumors of the distal stomach. Signet ring cell histology did not impact survival in our group of largely advanced gastric cancer cases. PMID:10515534

  15. High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma

    PubMed Central

    Sun, Peng; Yan, Shu-mei; Liu, Pan-pan; Li, Zhi-ming; Jiang, Wen-qi

    2016-01-01

    Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL. PMID:27032016

  16. 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

  17. Emotion malleability beliefs, emotion regulation, and psychopathology: Integrating affective and clinical science.

    PubMed

    Kneeland, Elizabeth T; Dovidio, John F; Joormann, Jutta; Clark, Margaret S

    2016-04-01

    Beliefs that individuals hold about whether emotions are malleable or fixed, also referred to as emotion malleability beliefs, may play a crucial role in individuals' emotional experiences and their engagement in changing their emotions. The current review integrates affective science and clinical science perspectives to provide a comprehensive review of how emotion malleability beliefs relate to emotionality, emotion regulation, and specific clinical disorders and treatment. Specifically, we discuss how holding more malleable views of emotion could be associated with more active emotion regulation efforts, greater motivation to engage in active regulatory efforts, more effort expended regulating emotions, and lower levels of pathological distress. In addition, we explain how extending emotion malleability beliefs into the clinical domain can complement and extend current conceptualizations of major depressive disorder, social anxiety disorder, and generalized anxiety disorder. This may prove important given the increasingly central role emotion dysregulation has been given in conceptualization and intervention for these psychiatric conditions. Additionally, discussion focuses on how emotion beliefs could be more explicitly addressed in existing cognitive therapies. Promising future directions for research are identified throughout the review. PMID:27086086

  18. Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management

    PubMed Central

    Ventriglio, Antonio; Gentile, Alessandro; Stella, Eleonora; Bellomo, Antonello

    2015-01-01

    Patients affected by psychotic disorders are more likely to develop high rates of co-morbidities, such as obesity, type 2 diabetes, dyslipidemias, hypertension, metabolic syndrome, myocardial infarction, stroke etc., in the long-term. These morbidities have a significant impact on the life-expectancy of these patients. Patients with chronic psychoses show a 2–3-fold increased risk of death mostly from cardiovascular and metabolic diseases. Although there may be an independent link, between schizophrenia and metabolic conditions the cardio-metabolic risk is mostly related to an unhealthy lifestyle and the usage of antipsychotic agents (especially Second Generation Antipsychotics or atypical) even when these remain effective treatments in the management of major psychoses. Recently, many international organizations have developed screening and monitoring guidelines for the control of modifiable risk factors in order to reduce the rate of co-morbidity and mortality among patients affected by schizophrenia. This paper is a review of current knowledge about the metabolic issues of patients affected by schizophrenia and describes clinical characteristics and medical management strategies for such conditions. PMID:26388714

  19. Clinical Integration and How It Affects Student Retention in Undergraduate Athletic Training Programs

    PubMed Central

    Young, Allison; Klossner, Joanne; Docherty, Carrie L; Dodge, Thomas M; Mensch, James M

    2013-01-01

    Context A better understanding of why students leave an undergraduate athletic training education program (ATEP), as well as why they persist, is critical in determining the future membership of our profession. Objective To better understand how clinical experiences affect student retention in undergraduate ATEPs. Design Survey-based research using a quantitative and qualitative mixed-methods approach. Setting Three-year undergraduate ATEPs across District 4 of the National Athletic Trainers' Association. Patients or Other Participants Seventy-one persistent students and 23 students who left the ATEP prematurely. Data Collection and Analysis Data were collected using a modified version of the Athletic Training Education Program Student Retention Questionnaire. Multivariate analysis of variance was performed on the quantitative data, followed by a univariate analysis of variance on any significant findings. The qualitative data were analyzed through inductive content analysis. Results A difference was identified between the persister and dropout groups (Pillai trace = 0.42, F1,92 = 12.95, P = .01). The follow-up analysis of variance revealed that the persister and dropout groups differed on the anticipatory factors (F1,92 = 4.29, P = .04), clinical integration (F1,92 = 6.99, P = .01), and motivation (F1,92 = 43.12, P = .01) scales. Several themes emerged in the qualitative data, including networks of support, authentic experiential learning, role identity, time commitment, and major or career change. Conclusions A perceived difference exists in how athletic training students are integrated into their clinical experiences between those students who leave an ATEP and those who stay. Educators may improve retention by emphasizing authentic experiential learning opportunities rather than hours worked, by allowing students to take on more responsibility, and by facilitating networks of support within clinical education experiences. PMID:23672327

  20. Analysis of donor heterogeneity as a factor affecting the clinical outcome of oocyte donation.

    PubMed

    Harris, Sarah E; Faddy, Malcolm; Levett, Stephen; Sharma, Vinay; Gosden, Roger

    2002-11-01

    This study investigated factors that may affect the clinical outcome of oocyte donation on the basis of data from a clinical programme involving 243 treatment cycles analysed retrospectively. In each cohort, oocytes were distributed randomly to one, two or three recipients, which enabled the outcomes in terms of pregnancy and live birth rates to be compared among donors. The results were compared with respect to age of the donor and recipient, number of oocytes collected, fertilization and cleavage rates, qualitative embryo criteria (morphological grade) and other clinical criteria. Most variables had no significant effect on either outcome, although the live birth rate varied inversely with recipient age. Unsurprisingly, the pregnancy rate was correlated positively with the number of embryos transferred. Most of the variation in pregnancy and live birth rates (85-90%) could not be accounted for by any specific donation characteristic, indicating that interdonor heterogeneity was the result of idiopathic factors. The factor most predictive of a recipient's cycle outcome was a history of previous success of the donor, which accounted for approximately 30% of the variation in live birth rates. Pregnancy success rates varied widely among oocyte donors, as has been found among sperm donors. This observation highlights the need to identify markers that predict developmental competence and help to identify the genetic and environmental bases of differential fertility. In conclusion, the quality of oocytes varied widely among women presumed to be fertile by clinical criteria, and the causative factors set a major limitation on the prospects of improving the outcome of egg donation. PMID:12477962

  1. Detecting Adverse Events Using Information Technology

    PubMed Central

    Bates, David W.; Evans, R. Scott; Murff, Harvey; Stetson, Peter D.; Pizziferri, Lisa; Hripcsak, George

    2003-01-01

    Context: Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. Objective: To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. Design: Structured review. Methodology: English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. Main Outcome Measures: Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. Results: Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. Conclusion: Computerized detection of adverse events will soon be practical on a widespread basis. PMID:12595401

  2. Early pregnancy vitamin D status and risk for adverse maternal and infant outcomes in a bi-ethnic cohort: the Behaviors Affecting Baby and You (B.A.B.Y.) Study.

    PubMed

    Nobles, Carrie J; Markenson, Glenn; Chasan-Taber, Lisa

    2015-12-28

    Vitamin D deficiency is common during pregnancy and higher in Hispanic as compared with non-Hispanic white women. However, the association between vitamin D deficiency and adverse pregnancy outcomes remains unclear and may vary across ethnic groups, in part because of genetic variation in the metabolism of vitamin D. Few studies have included Hispanic women. Therefore, we investigated this association among 237 participants in the Behaviors Affecting Baby and You Study, a randomised trial of an exercise intervention among ethnically diverse prenatal care patients in Massachusetts. Baseline serum 25-hydroxyvitamin D (25(OH)D) was measured at 15·2 (sd 4·7) weeks' gestation. Information on adverse pregnancy outcomes was abstracted from medical records. Mean 25(OH)D was 30·4 (sd 12·0) ng/ml; 53·2 % of participants had insufficient (<30 ng/ml) and 20·7 % had deficient (<20 ng/ml) 25(OH)D levels. After adjusting for month of blood draw, gestational age at blood draw, gestational age at delivery, age, BMI and Hispanic ethnicity, women with insufficient and deficient vitamin D had infants with birth weights 139·74 (se 69·16) g (P=0·045) and 175·52 (se 89·45) g (P=0·051) lower compared with women with sufficient vitamin D levels (≥30 ng/ml). Each 1 ng/ml increase in 25(OH)D was associated with an increased risk for gestational diabetes mellitus among Hispanic women only (relative risk 1·07; 95 % CI 1·03, 1·11) in multivariable analysis. We did not observe statistically significant associations between maternal vitamin D status and other pregnancy outcomes. Our findings provide further support for an adverse impact of vitamin D deficiency on birth weight in Hispanic women. PMID:26507186

  3. Virtual Reality for Enhanced Ecological Validity and Experimental Control in the Clinical, Affective and Social Neurosciences

    PubMed Central

    Parsons, Thomas D.

    2015-01-01

    An essential tension can be found between researchers interested in ecological validity and those concerned with maintaining experimental control. Research in the human neurosciences often involves the use of simple and static stimuli lacking many of the potentially important aspects of real world activities and interactions. While this research is valuable, there is a growing interest in the human neurosciences to use cues about target states in the real world via multimodal scenarios that involve visual, semantic, and prosodic information. These scenarios should include dynamic stimuli presented concurrently or serially in a manner that allows researchers to assess the integrative processes carried out by perceivers over time. Furthermore, there is growing interest in contextually embedded stimuli that can constrain participant interpretations of cues about a target’s internal states. Virtual reality environments proffer assessment paradigms that combine the experimental control of laboratory measures with emotionally engaging background narratives to enhance affective experience and social interactions. The present review highlights the potential of virtual reality environments for enhanced ecological validity in the clinical, affective, and social neurosciences. PMID:26696869

  4. Clinical factors affecting engraftment and transfusion needs in SCT: a single-center retrospective analysis.

    PubMed

    Liesveld, J; Pawlowski, J; Chen, R; Hyrien, O; Debolt, J; Becker, M; Phillips, G; Chen, Y

    2013-05-01

    Successful utilization of SCT modalities often requires utilization of both red cell and platelet transfusions. In this retrospective evaluation of clinical factors affecting transplant engraftment and transfusion utilization at a single transplant center in 505 patients from 2005 through 2009, we found that graft type, donor type and the conditioning regimen intensity significantly affected both the neutrophil engraftment time (P<0.001) and the platelet engraftment time (P<0.001). SCT patients required an average of 6.2 red cell units, and 7.9 platelet transfusions in the first 100 days with a wide s.d. Among auto-SCT patients, 5% required neither RBC nor platelet transfusions. Some reduced-intensity transplants were also associated with no transfusion need, and in allogeneic transplants, conditioning regimen intensity was positively correlated with platelet transfusion events as assessed by multivariate analysis. Other patient characteristics such as gender, graft type, donor type, underlying disease and use of TBI were all independently associated with transfusion needs in SCT patients. Further studies are required to understand the means to minimize transfusions and potential related complications in SCT patients. PMID:23085827

  5. Virus and Host Factors Affecting the Clinical Outcome of Bluetongue Virus Infection

    PubMed Central

    Caporale, Marco; Di Gialleonorado, Luigina; Janowicz, Anna; Wilkie, Gavin; Shaw, Andrew; Savini, Giovanni; Van Rijn, Piet A.; Mertens, Peter; Di Ventura, Mauro

    2014-01-01

    ABSTRACT Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence. IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected

  6. Does therapist’s attitude affect clinical outcome of lumbar facet joint injections?

    PubMed Central

    Middendorp, Marcus; Kollias, Konstantinos; Ackermann, Hanns; Splettstößer, Annina; Vogl, Thomas J; Khan, M Fawad; Maataoui, Adel

    2016-01-01

    AIM: To investigate if the clinical outcome of intra-articular lumbar facet joint injections is affected by the therapist’s attitude. METHODS: A total of 40 patients with facet joint-associated chronic low back pain were randomly divided into two groups. All patients received computed tomography-guided, monosegmental intra-articular facet joint injections. Following the therapeutic procedure, the patients of the experimental group (EG) held a conversation with the radiologist in a comfortable atmosphere. During the dialog, the patients were encouraged to ask questions and were shown four images. The patients of the control group (CG) left the clinic without any further contact with the radiologist. Outcome was assessed using a pain-based Verbal Numeric Scale at baseline, at 1 wk and at 1, 3, and 6 mo after first treatment. RESULTS: The patient demographics showed no differences between the groups. The patients of the EG received 57 interventional procedures in total, while the patients of the CG received 70 interventional procedures. In both groups, the pain scores decreased significantly over the entire observation period. Compared to the CG, the EG showed a statistically significant reduction of pain at 1 wk and 1 mo post-treatment, while at 3 and 6 mo after treatment, there were no significant differences between both groups. CONCLUSION: Our results show a significant effect on pain relief during the early post-interventional period in the EG as compared to the CG. The basic principle behind the higher efficacy might be the phenomenon of hetero-suggestion. PMID:27358691

  7. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  8. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  9. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  10. Sirtuin Inhibition Adversely Affects Porcine Oocyte Meiosis

    PubMed Central

    Zhang, Liang; Ma, Rujun; Hu, Jin; Ding, Xiaolin; Xu, Yinxue

    2015-01-01

    Sirtuins have been implicated in diverse biological processes, including oxidative stress, energy metabolism, cell migration, and aging. Here, we employed Sirtuin inhibitors, nicotinamide (NAM) and Sirtinol, to investigate their effects on porcine oocyte maturation respectively. The rate of polar body extrusion in porcine oocytes decreased after treatment with NAM and Sirtinol, accompanied with the failure of cumulus cell expansion. We further found that NAM and Sirtinol significantly disrupted oocyte polarity, and inhibited the formation of actin cap and cortical granule-free domain (CGFD). Moreover, the abnormal spindles and misaligned chromosomes were readily detected during porcine oocyte maturation after treatment with NAM and Sirtinol. Together, these results suggest that Sirtuins are involved in cortical polarity and spindle organization in porcine oocytes. PMID:26176547

  11. LITHIUM IN AFFECTIVE DISORDERS : A SEVEN YEAR OBSERVATION OF LITHIUM CLINIC

    PubMed Central

    Sethi, B.B.; Dalal, P.K.; Trivedi, J.K.

    1984-01-01

    SUMMARY Out of 692 patients registered in the lithium clinic, King George's Medical College, Lucknow, 122 patients suffering from affective disorders, receiving lithium for at least 6 months continuously, having had at least 5 serum lithium estimations done and having been evaluated at least once in 6 months while on follow-up, were analysed with a view to study the relapses. About one-third patients suffered no relapse while on lithium. The study revealed that longer the duration of lithium treatment lesser were the frequency, number, intensity and duration of manic/depressive relapses. Majority of patients were maintained on the lower side (0.5-0.8 mEq/L) of the usually recommended therapeutic range (0.6-1.2 mEq/L) for lithium prophylaxis. Commonly observed side effects include fine tremors, muscular weakness, polyuria, polydipsia and constipation. All the side effects were easily managed and none had a fatal sides-effect. A reappraisal in the light of existing literature of lithium prophylaxis on manic depressive psychosis is done. PMID:21966016

  12. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  13. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  14. Clinical findings in patients with anorexia nervosa and affective illness in their relatives.

    PubMed

    Gershon, E S; Schreiber, J L; Hamovit, J R; Dibble, E D; Kaye, W; Nurnberger, J I; Andersen, A E; Ebert, M

    1984-11-01

    The most prevalent psychiatric disorders in the families of patients with anorexia nervosa are bipolar and unipolar major affective disorder. The presence of affective disorder, self-induced vomiting, or bulimia in the patient is not predictive of affective illness in the relatives. Thus these features do not define genetic heterogeneity within anorexia nervosa. There may be genetic factors shared between anorexia nervosa and affective disorders. PMID:6496786

  15. Avoidance of Affect Mediates the Effect of Invalidating Childhood Environments on Borderline Personality Symptomatology in a Non-Clinical Sample

    ERIC Educational Resources Information Center

    Sturrock, Bonnie A.; Francis, Andrew; Carr, Steven

    2009-01-01

    The aim of this study was to test the Linehan (1993) proposal regarding associations between invalidating childhood environments, distress tolerance (e.g., avoidance of affect), and borderline personality disorder (BPD) symptoms. The sample consisted of 141 non-clinical participants (51 men, 89 women, one gender unknown), ranging in age from 18 to…

  16. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background 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. Description 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. Conclusion 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

  17. High birth weight in a suburban hospital in Cameroon: an analysis of the clinical cut-off, prevalence, predictors and adverse outcomes

    PubMed Central

    Choukem, Simeon-Pierre; Njim, Tsi; Atashili, Julius; Hamilton-Shield, Julian P; Mbu, Robinson

    2016-01-01

    Background and aims High birth weight (HBW) increases the risk of maternal and fetal morbidity and mortality. Its prevalence and adverse outcomes may be reduced if risk factors are identified and managed during pregnancy. The cut-off value for HBW remains debatable. The objectives of this study were to identify the optimal cut-off value and determine the prevalence, predictors and adverse outcomes of HBW in a suburban area of Cameroon. Design A 6-year retrospective register analysis and a 3-month prospective phase. Setting A secondary care level (regional) hospital in the city of Buea (southwest region of Cameroon). Participants Women who delivered in this hospital over a 6-year period (retrospective phase) and consenting pregnant mothers and their infants (singletons, born at >28 weeks gestation) (prospective phase). Outcome measures 90th centile of birth weights; prevalence of HBW defined as birth weight above the 90th centile; sociodemographic, maternal and obstetrical factors associated with HBW; maternal and neonatal adverse outcomes of HBW. Results Of the 4941 newborns reviewed in registers, the 90th centile of birth weights was 3850 g. Using this new cut-off, we obtained a prevalence of 14.0% for HBW in the 200 newborns included in the prospective phase. This was significantly higher than the prevalence (9.5%) yielded when the traditional cut-off of 4000 g was used (p=0.003). None of the factors assessed was independently associated with HBW. Newborns with HBW were more likely to have shoulder dystocia (p<0.01), and their mothers more likely to suffer from prolonged labour (p=0.01) and postpartum haemorrhage (p<0.01). Conclusions The results of this study suggest that the cut-off for HBW in this population should be 3850 g. Thus, 3 of every 10 babies born with HBW in this hospital are likely not receiving optimal postnatal care because 4000 g is currently used to qualify for additional support. PMID:27357199

  18. The Use of Vascular Closure Devices and Impact on Major Bleeding and Net Adverse Clinical Events (NACE) in Balloon Aortic Valvuloplasty: A Sub-Analysis of the BRAVO study

    PubMed Central

    O’Neill, Brian; Singh, Vikas; Kini, Annapoorna; Mehran, Roxana; Jacobs, Evan; Knopf, David; Alfonso, Carlos E.; Martinez, Claudia A.; Martinezclark, Pedro; O’Neill, William; Heldman, Alan W.; Yu, Jennifer; Baber, Usman; Kovacic, Jason; Dangas, George; Sharma, Samin; Sartori, Samantha; Cohen, Mauricio G.

    2013-01-01

    Objective To determine the impact of suture-mediated vascular closure devices on net adverse clinical events (NACE) after balloon aortic valvuloplasty (BAV). Background Ischemic and bleeding complications are common following transfemoral BAV however; previous studies have been single center and limited by varying definitions of major bleeding. Methods The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVO) study was a retrospective observational study conducted at two high-volume academic centers over a 6-year period designed to compare the effect of bivalirudin versus unfractionated heparin. This is a sub-analysis of 428 consecutive patients who underwent BAV (with 10-13 French sheaths) to compare the effect of hemostasis with vascular closure devices versus manual compression utilizing standardized definitions. NACE was defined as the composite of major bleeding and major adverse clinical events (MACE). All events were adjudicated by an independent clinical events committee who were blinded to antithrombin use. Results Pre-closure was performed in 269 (62.8%) of patients. While bivalirudin was used more frequently in those with pre-closure (60.6% vs. 37.7%, p<0.001), a history of prior BAV (11.1% vs. 3.6%, p=0.04) and peripheral vascular disease (30.7% vs. 19.7%, p=0.01) was more common in those not undergoing pre-closure (n=159, 37%). Other clinical and demographic features were well balanced between groups. Vascular closure was associated with a significant reduction in NACE (24.5% vs 10.0% p<0.001). Results remained significant after adjusting for baseline differences and bivalirudin use (OR 0.38, 95% CI: 0.21 - 0.68; p=0.001). Conclusions Our study suggests that suture-mediated vascular closure is associated with a substantial reduction in NACE after transfemoral BAV. Large randomized clinical trials should be conducted to confirm our results. PMID:23436434

  19. 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; Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward; Sahgal, Arjun

    2013-07-15

    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 analgesic 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.

  20. Does medical students’ clinical performance affect their actual performance during medical internship?

    PubMed Central

    Han, Eui-Ryoung; Chung, Eun-Kyung

    2016-01-01

    INTRODUCTION This study examines the relationship between the clinical performance of medical students and their performance as doctors during their internships. METHODS This retrospective study involved 63 applicants of a residency programme conducted at Chonnam National University Hospital, South Korea, in November 2012. We compared the performance of the applicants during their internship with their clinical performance during their fourth year of medical school. The performance of the applicants as interns was periodically evaluated by the faculty of each department, while their clinical performance as fourth-year medical students was assessed using the Clinical Performance Examination (CPX) and the Objective Structured Clinical Examination (OSCE). RESULTS The performance of the applicants as interns was positively correlated with their clinical performance as fourth-year medical students, as measured by the CPX and OSCE. The performance of the applicants as interns was moderately correlated with the patient-physician interaction items addressing communication and interpersonal skills in the CPX. CONCLUSION The clinical performance of medical students during their fourth year in medical school was related to their performance as medical interns. Medical students should be trained to develop good clinical skills through actual encounters with patients or simulated encounters using manikins, to enable them to become more competent doctors. PMID:26768172

  1. Cognitive Set and Clinical Inference: Referral Information May Not (Always) Affect Psychosocial Assessment.

    ERIC Educational Resources Information Center

    Abraham, Ivo L.

    1986-01-01

    Studied the effects of general referral information about a client on subsequent clinical inferences. Nursing students (N=54) were randomly assigned to "referral information" or "no referral information" conditions before being presented with additional data. Clinical inferential tasks included the assessment of maladjustment, client stress,…

  2. Exploring Factors Affecting Undergraduate Medical Students' Study Strategies in the Clinical Years: A Qualitative Study

    ERIC Educational Resources Information Center

    Al Kadri, Hanan M. F.; Al-Moamary, Mohamed S.; Elzubair, Margaret; Magzoub, Mohi Eldien; AlMutairi, Abdulrahman; Roberts, Christopher; van der Vleuten, Cees

    2011-01-01

    The aim of this study is to explore the effects of clinical supervision, and assessment characteristics on the study strategies used by undergraduate medical students during their clinical rotations. We conducted a qualitative phenomenological study at King Saud Bin Abdulaziz University for Health Sciences, College of Medicine, Riyadh, Saudi…

  3. Subliminal affective priming in clinical depression and comorbid anxiety: a longitudinal investigation.

    PubMed

    Dannlowski, Udo; Kersting, Anette; Lalee-Mentzel, Judith; Donges, Uta-Susan; Arolt, Volker; Suslow, Thomas

    2006-06-30

    In the present study, the sequential affective priming paradigm developed by Fazio et al. [Fazio, R.H., Sanbonmatsu, D.M., Powell, M.C., Kardes, F.R., 1986. On the automatic activation of attitudes. Journal of Personality and Social Psychology 50, 229-238.] was applied for the first time to investigate automatic cognitive bias in depressed patients. Unipolar depressed patients (n=22) were tested on admission and after about 7 weeks of inpatient psychotherapy. Half of the patients (n=11) were suffering from a comorbid anxiety disorder. Twenty-two healthy subjects served as controls. Affectively polarized prime words were presented subliminally followed by positive or negative target words, which had to be evaluated. Subjects' affective state was assessed by self-report measures. In the course of psychotherapy, patients recovered significantly. Study groups exhibited qualitatively different affective priming effects: In non-comorbid depressed patients, no affective priming was found. Instead, a highly significant main effect of prime valence emerged, indicating a Stroop-like interference of negative prime words at time 1. This negative bias was associated with depression level at time 1 and could not be found after recovery. Affective priming was observed in controls and comorbid patients, but in opposite directions. Direction and strength of affective priming was directly associated with anxiety level at both times. The affective priming paradigm provides evidence for differential group effects regarding unconscious emotional information processing. PMID:16725208

  4. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  5. 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 Central

    Valadares, Fabiana; Garbi Novaes, Maria Rita Carvalho; Cañete, Roberto

    2013-01-01

    Background: 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. Aim: To evaluate the effects of dietary supplementation of Agaricus sylvaticus on clinical and nutritional parameters in BC patients undergoing chemotherapy. Materials and Methods: 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. Results: 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%). Conclusion: Dietary supplementation with A. sylvaticus improved nutritional status and reduced abnormal bowel functions, nausea, vomiting, and anorexia in patients with BC receiving chemotherapy. PMID:23833361

  6. Parental emotion socialization in clinically depressed adolescents: Enhancing, and dampening positive affect

    PubMed Central

    Katz, Lynn Fainsilber; Shortt, Joann Wu; Allen, Nicholas B.; Davis, Betsy; Hunter, Erin; Leve, Craig; Sheeber, Lisa

    2013-01-01

    This study compared parental socialization of adolescent positive affect in families of depressed and healthy adolescents. Participants were 107 adolescents (42 boys) aged 14 - 18 years and their parents. Half of the participants met criteria for major depressive disorder and the others were demographically matched adolescents without emotional or behavioral disorders. Results based on multi-source questionnaire and interview data indicated that mothers and fathers of depressed adolescents were less accepting of adolescents’ positive affect and more likely to use strategies that dampen adolescents’ positive affect than were parents of healthy adolescents. Additionally, fathers of depressed adolescents exhibited fewer responses likely to enhance the adolescents’ positive affect than were fathers of healthy adolescents. These findings build on those of previous work in examining parental responses to adolescent emotions, focusing on positive emotions and including both mothers and fathers. PMID:23942826

  7. Cutaneous adverse reactions of imatinib therapy in patients with chronic myeloid leukemia: A six-year follow up.

    PubMed

    Dervis, Emine; Ayer, Mesut; Akin Belli, Asli; Barut, Saime Gul

    2016-04-01

    Imatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Cutaneous adverse reactions of imatinib therapy have been reported in 7%-88.9% patients. We sought to evaluate the prevalence rates of cutaneous adverse reactions of imatinib therapy and to investigate the clinical and pathological characteristics of these reactions. Sixty-six patients (36 men, 30 women; age range 19-83 years) with CML treated with imatinib between 2008 and 2014 were included in the study. Clinical and pathological features of the adverse reactions were investigated. Cutaneous adverse reactions were the most common adverse effects of imatinib therapy and were seen in nine patients with a prevalence rate of 13.6%. The second most common adverse effect was musculoskeletal pain (12.1%). The following cutaneous reactions were observed in patients: edema, rash, pigmentary changes, aphthous stomatitis, alopecia, cutaneous dryness, hyperhidrosis and cheilitis. Imatinib therapy was discontinued in four patients because of various adverse effects. Although the prevalence rate of cutaneous adverse reactions in our study was lower than that in several other studies, cutaneous reactions were common in our study. The relatively low prevalence rate of adverse reactions may be related to the low dosage of imatinib (400 mg/day) used to treat our patients and may have been affected by pharmacogenetic characteristics of our population. PMID:26679005

  8. 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. PMID:26645393

  9. Extreme sensory processing patterns and their relation with clinical conditions among individuals with major affective disorders.

    PubMed

    Engel-Yeger, Batya; Muzio, Caterina; Rinosi, Giorgio; Solano, Paola; Geoffroy, Pierre Alexis; Pompili, Maurizio; Amore, Mario; Serafini, Gianluca

    2016-02-28

    Previous studies highlighted the involvement of sensory perception in emotional processes. However, the role of extreme sensory processing patterns expressed in hyper- or hyposensitivity was not thoroughly considered. The present study, in real life conditions, examined the unique sensory processing patterns of individuals with major affective disorders and their relationship with psychiatric symptomatology. The sample consisted of 105 participants with major affective conditions ranging in age from 20 to 84 years (mean=56.7±14.6). All participants completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A), the second version of the Beck Depression Inventory (BDI-II), and Adolescent/Adult Sensory Profile (AASP). Sensory sensitivity/avoiding hypersensitivity patterns and low registration (a hyposensitivity pattern) were prevalent among our sample as compared to normative data. About seventy percent of the sample showed lower seeking tendency. Stepwise regression analyses revealed that depression and anxious/cyclothymic affective temperaments were predicted by sensory sensory/avoiding. Anxious and irritable affective temperaments were predicted by low registration. Hyperthymic affective temperament and lower severity of depression were predicted by sensation seeking. Hyposensitivity or hypersensitivity may be "trait" markers of individuals with major affective disorders. Interventions should refer to the individual unique sensory profiles and their behavioral and functional impact in the context of real life. PMID:26738981

  10. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  11. Mid-Trimester Maternal Serum hCG and Alpha Fetal Protein Levels: Clinical Significance and Prediction of Adverse Pregnancy Outcome

    PubMed Central

    Androutsopoulos, Georgios; Gkogkos, Panagiotis; Decavalas, Georgios

    2013-01-01

    Context Maternal serum human Chorionic Gonadotropin (hCG) and Alpha Fetal Protein (AFP) were originally introduced to detect trisomy 21 and neural tube defects. However, in the absence of aneuploidy or neural tube defects, mid-trimester maternal serum hCG and/or maternal serum AFP associated with adverse pregnancy outcomes. Pregnancies with unexplained mid-trimester elevation in maternal serum hCG and/or maternal serum AFP, are at increased risk for pregnancy complications resulting from placental insufficiency. Evidence Acquisition Mid-trimester maternal serum hCG>2.5 MoM associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, intrauterine growth restriction (IUGR), preterm delivery and intrauterine fetal death(IUFD). Mid-trimester maternal serum AFP levels >2.5 MoM are thought to reflect a defect in placentation and associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. Results Combined mid-trimester elevation in maternal serum hCG and AFP levels suggest a more complex type of placental pathology. They have stronger association with pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. Conclusions Mid-trimester maternal serum hCG or AFP levels alone cannot detect all pregnant women with increased risk to develop pregnancy complications. Multiparameter testing of placental function in mid-trimester (maternal serum hCG and AFP screening, uterine artery Doppler and placental morphology) may allow us to identify women with increased risk to develop severe placental insufficiency and pregnancy complications. However, future prospective studies are needed to confirm the prognostic significance of multiparameter testing of placental function in mid-trimester. PMID:23825981

  12. 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

  13. Histopathological investigation of clinically non-affected perilesional scalp in alopecias detected unexpected spread of disease activities.

    PubMed

    Watanabe-Okada, Emiko; Amagai, Masayuki; Ohyama, Manabu

    2014-09-01

    Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non-affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4-mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non-affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions. PMID:25156442

  14. [Affection, proximity, frequency and hesitant clinical practice: basis of the "bond" between Down syndrome patients and primary health care?].

    PubMed

    Fontanella, Bruno José Barcellos; Setoue, Cesar Seiji; Melo, Débora Gusmão

    2013-07-01

    The national policy of comprehensive care in clinical genetics propounds that families and individuals with genetic disorders should receive ongoing assistance at primary health care (PHC) level. In this study, the social representation of professionals working in family health care units (FHCU) is investigated based on their "bond" with Down syndrome patients, bearing in mind that this expression currently contains relevant meanings in the clinical practice and service management routine. Sixteen practitioners were interviewed, and the sample was defined by theoretical saturation. The statements given by the participants expressed knowledge based mainly on affective skills, physical proximity and patients' frequency of attendance at the family health care unit (FHCU). Clinical skills of other kinds, especially cognitive skills, do not appear to justify the notion of "bond." The results indicate the need of continuous professional education and definition of guidelines and approaches in care to the most common syndromes in the context of primary health care (PHC). PMID:23827892

  15. The Influence of Context on Residents' Evaluations: Effects of Priming on Clinical Judgment and Affect

    ERIC Educational Resources Information Center

    Teunissen, P. W.; Stapel, D. A.; Scheele, F.; Scherpbier, A. J. J. A.; Boor, K.; van Diemen-Steenvoorde, J. A. A. M.; van der Vleuten, C. P. M.

    2009-01-01

    Different lines of research have suggested that context is important in acting and learning in the clinical workplace. It is not clear how contextual information influences residents' constructions of the situations in which they participate. The category accessibility paradigm from social psychology appears to offer an interesting perspective for…

  16. Client Preferences Affect Treatment Satisfaction, Completion, and Clinical Outcome: A Meta-Analysis

    PubMed Central

    Lindhiem, Oliver; Bennett, Charles B.; Trentacosta, Christopher J.; McLear, Caitlin

    2014-01-01

    We conducted a meta-analysis on the effects of client preferences on treatment satisfaction, completion, and clinical outcome. Our search of the literature resulted in 34 empirical articles describing 32 unique clinical trials that either randomized some clients to an active choice condition (shared decision making condition or choice of treatment) or assessed client preferences. Clients who were involved in shared decision making, chose a treatment condition, or otherwise received their preferred treatment evidenced higher treatment satisfaction (ESd = .34; p < .001), increased completion rates (ESOR = 1.37; ESd = .17; p < .001), and superior clinical outcome (ESd = .15; p < .0001), compared to clients who were not involved in shared decision making, did not choose a treatment condition, or otherwise did not receive their preferred treatment. Although the effect sizes are modest in magnitude, they were generally consistent across several potential moderating variables including study design (preference versus active choice), psychoeducation (informed versus uninformed), setting (inpatient versus outpatient), client diagnosis (mental health versus other), and unit of randomization (client versus provider). Our findings highlight the clinical benefit of assessing client preferences, providing treatment choices when two or more efficacious options are available, and involving clients in treatment-related decisions when treatment options are not available. PMID:25189522

  17. Social and Demographic Factors Affecting Psychopathology and Substance Abuse in a Spanish Family Clinic Population.

    ERIC Educational Resources Information Center

    Ladner, Robert A.

    This report presents findings on the social and demographic factors associated with drug abuse, alcoholism, and major psychological impairment in a population of Cuban American patients presenting at the Spanish Family Guidance Clinic (Miami, Florida) in 1974-75. The analysis indicates a number of factors operating to increase the likelihood of…

  18. Ruby laser for treatment of tattoos: technical considerations affecting clinical use

    NASA Astrophysics Data System (ADS)

    Grove, Robert E.

    1990-06-01

    Recent clinical research on the use of ruby lasers for the treatment of tattoos and FIlk approval of a commercial system have renewed interest in this device. In this paper the principles of Q-switched ruby laser operation are reviewed, and potential sources of error in the estimation of delivered fluence are discussed.

  19. Changes in disengagement coping mediate changes in affect following mindfulness-based cognitive therapy in a non-clinical sample.

    PubMed

    Cousin, Gaëtan; Crane, Catherine

    2016-08-01

    Past research has shown that mindfulness-based interventions increase positive affect in non-clinical populations. However, the mechanisms underlying this increase are poorly understood. On the basis of previous empirical and theoretical accounts, we hypothesized that a decreased use of disengagement coping strategies in daily life would explain the benefits of a mindfulness-based intervention in terms of increased positive affect. We analysed the data of 75 healthy adult participants (58 women; 17 men) of different ages (M = 49 years old; SD = 13; age range 19-81) who had been randomly allocated to 8-week Mindfulness-Based Cognitive Therapy (MBCT) or to a waitlist control group. The results confirmed our hypothesis: Participants in the MBCT group showed significant improvements in positive affect compared to the control group, with decreased use of disengagement coping styles mediating these improvements. The implications of this study are discussed. PMID:26385256

  20. Affective Neural Responses Modulated by Serotonin Transporter Genotype in Clinical Anxiety and Depression

    PubMed Central

    Oathes, Desmond J.; Hilt, Lori M.; Nitschke, Jack B.

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/LG carriers showed less activity than their LA/LA counterparts in both regions and less activity than S/LG healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  1. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.

    PubMed

    Pan, Xiaoxia; Ouyang, Yan; Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  2. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

    PubMed Central

    Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  3. Commentary: a practical guide for translating basic research on affective science to implementing physiology in clinical child and adolescent assessments.

    PubMed

    Aldao, Amelia; De Los Reyes, Andres

    2015-01-01

    The National Institute of Mental Health recently launched the Research Domain Criteria (RDoC). RDoC is a framework that facilitates the dimensional assessment and classification of processes relevant to mental health (e.g., affect, regulation, cognition, social affiliation), as reflected in measurements across multiple units of analysis (e.g., physiology, circuitry, genes, self-reports). A key focus of RDoC involves opening new lines of research examining patients' responses on biological measures, with the key goal of developing new therapeutic techniques that effectively target mechanisms of mental disorders. Yet applied researchers and practitioners rarely use biological measures within mental health assessments, which may present challenges in translating RDoC-guided research into improvements in patient care. Thus, if RDoC is to result in research that yields clinical tools that reduce the burden of mental illness and improve public health, we ought to develop strategies for effectively implementing biological measures in the context of clinical assessments. In this special issue, we sought to provide an initial step in this direction by assembling a collection of articles from leading research teams carrying out pioneering work on implementing multimodal assessments (biological, subjective, behavioral) of affective processes in applied settings. In this commentary, we expand upon the work presented in this special issue by making a series of suggestions for how to most parsimoniously conduct multimodal assessments of affective processes in applied research and clinical settings. We hope that this approach will facilitate translations of the RDoC framework into applied research and clinic settings. PMID:25664768

  4. Evaluation of Factors Affecting Continuous Performance Test Identical Pairs Version Score of Schizophrenic Patients in a Japanese Clinical Sample

    PubMed Central

    Koide, Takayoshi; Aleksic, Branko; Kikuchi, Tsutomu; Banno, Masahiro; Kohmura, Kunihiro; Adachi, Yasunori; Kawano, Naoko; Iidaka, Tetsuya; Ozaki, Norio

    2012-01-01

    Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP), which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit) and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS) scores) in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d′ score in patients. These three clinical factors explained about 28% of the variance in mean d′ score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score. PMID:22966454

  5. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition. PMID:26934738

  6. Affective neural responses modulated by serotonin transporter genotype in clinical anxiety and depression.

    PubMed

    Oathes, Desmond J; Hilt, Lori M; Nitschke, Jack B

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L(G) carriers showed less activity than their L(A)/L(A) counterparts in both regions and less activity than S/L(G) healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  7. Pierre Robin Sequence: A Familial, Clinical, and Pathoanatomical Record of an Affected Dachshund.

    PubMed

    Moura, Enio; Wagner, José L; Cirio, Silvana M; Pimpão, Cláudia T

    2015-01-01

    This study describes a spontaneous case of Pierre Robin sequence in a nonhuman animal species. A miniature dachshund with micrognathia developed glossoptosis, respiratory distress, dysphagia, temporomandibular ankylosis, and a misaligned upper jaw. The severity of this condition resulted in death by obstructive apnea at the age of 8 mo. Dogs with Pierre Robin sequence can provide further knowledge and a greater understanding of this abnormality, leading to better management of affected individuals and improvement of therapeutic methods. PMID:26355589

  8. Considerations on assisted resilience and individualized therapy in bipolar affective disorder, with a clinical case exemplification

    PubMed Central

    BOLOS, ALEXANDRA

    2015-01-01

    Morbidity, mortality and economic consequences of bipolar affective disorder are very important to be evaluated because many of the costs entailed by this psychiatric disorder come from indirect costs due to inadequate diagnosis and treatment and from the characteristics of the affective symptoms itself. Psychotherapy focuses on diagnosis and the newest pharmacotherapy determines a decreasing of the morbidity of the disorder and also of its social and economic burden. However, more studies are necessary, with more heterogeneous patients, to find more predictors regarding the psychosocial consequences and to find more information about the prognosis of the bipolar disorder. In this context, in this paper we discuss the role of assisted resilience and the individualization of the therapy of bipolar affective disorder, especially that the resilience must be seen as a continuum and can be used anytime and in any situation, according to the theory of Geanellos. This idea is reflected in a case presentation of a patient with the diagnosis of bipolar disorder. PMID:26733744

  9. Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population

    PubMed Central

    Yoo, Seung Don; Yun, Dong Hwan; Kim, Hee-Sang; Kim, Su Kang; Kim, Dong Hwan; Chon, Jinmann; Je, Goun; Kim, Yoon-Seong; Chung, Joo-Ho; Chung, Seung Joon; Yeo, Jin Ah

    2016-01-01

    Objective To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke. Methods We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data. Results No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models. Conclusion These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population. PMID:26949676

  10. Pain and Other Non-Neurological Adverse Events in Children with Sickle Cell Anemia and Previous Stroke who Received Hydroxyurea and Phlebotomy or Chronic Transfusions and Chelation: Results from the SWiTCH Clinical Trial

    PubMed Central

    Alvarez, Ofelia; Yovetich, Nancy A.; Scott, J. Paul; Owen, William; Miller, Scott T.; Schultz, William; Lockhart, Alexandre; Aygun, Banu; Flanagan, Jonathan; Bonner, Melanie; Mueller, Brigitta U.; Ware, Russell E.

    2014-01-01

    Purpose To compare the non-neurological events in children with sickle cell anemia (SCA) and previous stroke enrolled in SWiTCH. Methods The NHLBI-sponsored Phase III multicenter randomized clinical trial Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) (ClinicalTrials.gov NCT00122980) compared continuation of chronic blood transfusion/iron chelation to switching to hydroxyurea/phlebotomy for secondary stroke prevention and management of iron overload. All randomized children were included in the analysis (intention to treat). The Fisher's Exact test was used to compare the frequency of subjects who experienced at least one SCA-related adverse event (AE) or serious adverse event (SAE) in each arm and to compare event rates. Results 133 subjects, mean age 13 ±3.9 years (range 5.2-19.0 years) and mean time of 7 years on chronic transfusion at study entry, were randomized and treated. Numbers of subjects experiencing non-neurological AEs were similar in the two treatment arms, including SCA-related events, SCA pain events, and low rates of acute chest syndrome and infection. However, fewer children continuing transfusion/chelation experienced SAEs (p=0.012), SCA-related SAEs (p=0.003), and SCA pain SAEs (p=0.016) as compared to children on the hydroxyurea/phlebotomy arm. The timing of phlebotomy did not influence SAEs. Older age at baseline predicted having at least 1 SCA pain event. Patients with recurrent neurological events during SWiTCH were not more likely to experience pain. Conclusions In children with SCA and prior stroke, monthly transfusions and daily iron chelation provided superior protection against acute vaso-occlusive pain SAEs when compared to hydroxyurea and monthly phlebotomy. PMID:23861242

  11. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  12. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials

    PubMed Central

    Jin, Xia; Morgan, Cecilia; Yu, Xuesong; DeRosa, Stephen; Tomaras, Georgia D.; Montefiori, David C.; Kublin, James; Corey, Larry; Keefer, Michael C.

    2015-01-01

    Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8% to 17.8%) and 37.7% (95% CI: 31.9% to 43.8%) of vaccine recipients, respectively. Three vaccinations (versus 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower Body Mass Index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials. PMID:25820067

  13. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.

    PubMed

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-04-19

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma.Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines.We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK.Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%.Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression.Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants.In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  14. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    PubMed Central

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  15. How can usability measurement affect the re-engineering process of clinical software procedures?

    PubMed

    Terazzi, A; Giordano, A; Minuco, G

    1998-01-01

    As a consequence of the dramatic improvements achieved in information technology standards in terms of single hardware and software components, efforts in the evaluation processes have been focused on the assessment of critical human factors, such as work-flow organisation, man-machine interaction and, in general, quality of use, or usability. This trend is particularly valid when applied to medical informatics, since the human component is the basis of the information processing system in health care context. With the aim to establish an action-research project on the evaluation and assessment of clinical software procedures which constitute an integrated hospital information system, the authors adopted this strategy and considered the measurement of perceived usability as one of the main goals of the project itself: the paper reports the results of this experience. PMID:9848419

  16. Factors affecting the postoperative limb alignment and clinical outcome after Oxford unicompartmental knee arthroplasty.

    PubMed

    Kim, Seung-Ju; Bae, Ji-Hoon; Lim, Hong Chul

    2012-06-01

    We evaluated the postoperative mechanical axis deviation and clinical outcome according to bearing size, femoral component position, and tibial resection angle after unicompartmental knee arthroplasty (UKA). A total of 104 patients with 124 knees underwent Oxford phase 3 UKA. The overall changes in mechanical axis deviation and tibiofemoral angle were significantly different according to bearing size (P = .001 and < .001), but they were not significantly different according to the tibial resection angle and femoral component position. The postoperative mechanical axis fell into the zone C or zone 2 in 108 knees (87%) and into the zone 3 or zone 4 in 16 cases (13%). One hundred eight cases, which had the mechanical axis passing the zone C or zone 2, did not show any progression of arthritis. Limb alignment is a function of the thickness of the bearing rather than alignments of femoral and tibial implant. PMID:22285234

  17. Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

    PubMed Central

    Severson, Tyler J; Besur, Siddesh; Bonkovsky, Herbert L

    2016-01-01

    AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review. METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur. RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine. CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management. PMID:27547017

  18. Clinical and radiological factors affecting progressive collapse of acute osteoporotic compression spinal fractures.

    PubMed

    Goldstein, Sergei; Smorgick, Yossi; Mirovsky, Yigal; Anekstein, Yoram; Blecher, Ronen; Tal, Sigal

    2016-09-01

    Osteoporotic compression spine fractures have a different clinical course and outcomes when compared to spinal fractures occurring in the younger population. Only a few studies have investigated the risk factors for progressive osteoporotic compression spine fractures. The purpose of this study was to investigate clinical and radiological factors related to progressive collapse following acute osteoporotic compression spine fractures. We retrospectively identified all patients treated for thoracolumbar fractures in our institution between January 2008 and July 2013. Included cases were examined by plain radiographs and CT scans. For each patient we classified the fracture according to the AOSpine Thoracolumbar Spine Injury Classification System. The difference between initial and final height loss and initial and final local kyphosis was documented as height loss difference and kyphotic angle difference. The presence of old fractures and intravertebral cleft were also documented. The study included 153 patients, comprising 102 women and 51 men. The mean patient age was 68.9years. The mean length of follow up was 15months. A statistically significant correlation was found between patient age, final height loss, height loss difference and kyphotic angle difference. Height loss difference and kyphotic angle difference were significantly correlated to type of fracture according to the AO classification system. The height loss difference was 18.1% in A1 type fractures, 27.1% in A2 type fractures, 24.2% in A3 type fractures and 25.7% in A4 type fractures. During a minimum 3-month follow up of conservative treatment for acute osteoporotic vertebral compression fractures, age and the AOSpine Thoracolumbar Spine Injury Classification System were predictive factors for progressive collapse. PMID:27387197

  19. Verbal conditioning of affect responses of process and reactive schizophrenics in a clinical interview situation.

    PubMed

    Pansa, M

    1979-06-01

    Sixteen process and 16 reactive schizoprenics out-patients were compared on a verbal conditioning task in an alternating conditioning-extinction design, using verbal and non-verbal positive social reinforcement to influence the emission of self-referred affect statements. It was found that process subjects failed to condition during the time periods used, while reactives demonstrated a significant trials effect showing trends consistent with those hypothesized from the type of design used. This differential conditionability between groups was shown not to be a function of diagnosis, sex, motivation, severity of illness, medication, hospitalization history, or general speech output. It was concluded that the degree of social responsiveness manifested in the premorbid history of the two groups is also operative in behaviour during the psychotic period, specifically, in responsiveness to positive social reinforcers in a verbal conditioning task. PMID:486358

  20. Deficits of Affect Mentalization in Patients with Drug Addiction: Theoretical and Clinical Aspects

    PubMed Central

    Savov, Svetoslav; Atanassov, Nikola

    2013-01-01

    Traditionally treated with wariness, drug addictions have provoked a serious interest in psychodynamically oriented clinicians in recent decades. This paper discusses the development of contemporary psychodynamic conceptualizations of addictions, focusing specifically on mentalization-based theories. The concept of mentalization refers to a complex form of self-regulation which includes attribution of psychological meaning to one's own behavior and affective states, as well as those of the others. We hypothesize that drug-addicted patients have severe impairments in mentalizing, associated with developmental deficits, characteristic for the borderline personality disorder and psychosomatic conditions. Psychodynamic models of mentalization and their corresponding research operationalizations are reviewed, and implications for a contemporary understanding of drug addictions and psychotherapy are drawn. The authors propose that mentalization-oriented theories provide an adequate conceptualization, which is open to empirical testing and has clear and pragmatic guidelines for treatment. PMID:25969831

  1. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    PubMed

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  2. Psychogenic fever: how psychological stress affects body temperature in the clinical population

    PubMed Central

    Oka, Takakazu

    2015-01-01

    Psychogenic fever is a stress-related, psychosomatic disease especially seen in young women. Some patients develop extremely high core body temperature (Tc) (up to 41°C) when they are exposed to emotional events, whereas others show persistent low-grade high Tc (37–38°C) during situations of chronic stress. The mechanism for psychogenic fever is not yet fully understood. However, clinical case reports demonstrate that psychogenic fever is not attenuated by antipyretic drugs, but by psychotropic drugs that display anxiolytic and sedative properties, or by resolving patients' difficulties via natural means or psychotherapy. Animal studies have demonstrated that psychological stress increases Tc via mechanisms distinct from infectious fever (which requires proinflammatory mediators) and that the sympathetic nervous system, particularly β3-adrenoceptor-mediated non-shivering thermogenesis in brown adipose tissue, plays an important role in the development of psychological stress-induced hyperthermia. Acute psychological stress induces a transient, monophasic increase in Tc. In contrast, repeated stress induces anticipatory hyperthermia, reduces diurnal changes in Tc, or slightly increases Tc throughout the day. Chronically stressed animals also display an enhanced hyperthermic response to a novel stress, while past fearful experiences induce conditioned hyperthermia to the fear context. The high Tc that psychogenic fever patients develop may be a complex of these diverse kinds of hyperthermic responses. PMID:27227051

  3. Psychogenic fever: how psychological stress affects body temperature in the clinical population.

    PubMed

    Oka, Takakazu

    2015-01-01

    Psychogenic fever is a stress-related, psychosomatic disease especially seen in young women. Some patients develop extremely high core body temperature (Tc) (up to 41°C) when they are exposed to emotional events, whereas others show persistent low-grade high Tc (37-38°C) during situations of chronic stress. The mechanism for psychogenic fever is not yet fully understood. However, clinical case reports demonstrate that psychogenic fever is not attenuated by antipyretic drugs, but by psychotropic drugs that display anxiolytic and sedative properties, or by resolving patients' difficulties via natural means or psychotherapy. Animal studies have demonstrated that psychological stress increases Tc via mechanisms distinct from infectious fever (which requires proinflammatory mediators) and that the sympathetic nervous system, particularly β3-adrenoceptor-mediated non-shivering thermogenesis in brown adipose tissue, plays an important role in the development of psychological stress-induced hyperthermia. Acute psychological stress induces a transient, monophasic increase in Tc. In contrast, repeated stress induces anticipatory hyperthermia, reduces diurnal changes in Tc, or slightly increases Tc throughout the day. Chronically stressed animals also display an enhanced hyperthermic response to a novel stress, while past fearful experiences induce conditioned hyperthermia to the fear context. The high Tc that psychogenic fever patients develop may be a complex of these diverse kinds of hyperthermic responses. PMID:27227051

  4. Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.

    PubMed

    Bilski, Jan; Mazur-Bialy, Agnieszka; Brzozowski, Bartosz; Magierowski, Marcin; Zahradnik-Bilska, Janina; Wójcik, Dagmara; Magierowska, Katarzyna; Kwiecien, Slawomir; Mach, Tomasz; Brzozowski, Tomasz

    2016-08-01

    The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models. PMID:27255494

  5. Biased Recognition of Facial Affect in Patients with Major Depressive Disorder Reflects Clinical State

    PubMed Central

    Münkler, Paula; Rothkirch, Marcus; Dalati, Yasmin; Schmack, Katharina; Sterzer, Philipp

    2015-01-01

    Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait. PMID:26039710

  6. Client Factors Affect Provider Adherence to Clinical Guidelines during First Antenatal Care

    PubMed Central

    Agyepong, Irene Akua; Zuithoff, Nicolaas P. A.; Kayode, Gbenga A; Grobbee, Diederick E; Klipstein-Grobusch, Kerstin; Ansah, Evelyn K

    2016-01-01

    Background The first antenatal clinic (ANC) visit helps to distinguish pregnant women who require standard care, from those with specific problems and so require special attention. There are protocols to guide care providers to provide optimal care to women during ANC. Our objectives were to determine the level of provider adherence to first antenatal visit guidelines in the Safe Motherhood Protocol (SMP), and assess patient factors that determine complete provider adherence. Methods This cross-sectional study is part of a cohort study that recruited women who delivered in eleven health facilities and who had utilized antenatal care services during their pregnancy in the Greater Accra region of Ghana. A record review of the first antenatal visit of participants was carried out to assess the level of adherence to the SMP, using a thirteen-point checklist. Information on their socio-demographic characteristics and previous pregnancy history was collected using a questionnaire. Percentages of adherence levels and baseline characteristics were estimated and cluster-adjusted odds ratios (OR) calculated to identify determinants. Results A total of 948 women who had delivered in eleven public facilities were recruited with a mean age (SD) of 28.2 (5.4) years. Overall, complete adherence to guidelines pertained to only 48.1% of pregnant women. Providers were significantly more likely to completely adhere to guidelines when caring for multiparous women [OR = 5.43 (1.69–17.44), p<0.01] but less likely to do so when attending to women with history of previous pregnancy complications [OR = 0.50 (0.33–0.75), p<0.01]. Conclusion Complete provider adherence to first antenatal visit guidelines is low across different facility types in the Greater Accra region of Ghana and is determined by parity and history of previous pregnancy complication. Providers should be trained and supported to adhere to the guidelines during provision of care to all pregnant women. PMID:27322643

  7. Biased recognition of facial affect in patients with major depressive disorder reflects clinical state.

    PubMed

    Münkler, Paula; Rothkirch, Marcus; Dalati, Yasmin; Schmack, Katharina; Sterzer, Philipp

    2015-01-01

    Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait. PMID:26039710

  8. Clinical and Pharmacogenetic Factors Affecting Neonatal Bilirubinemia Following Atazanavir Treatment of Mothers During Pregnancy

    PubMed Central

    Huang, Shu-Pang; Conradie, Francesca; Zorrilla, Carmen D.; Josipovic, Deirdre; Botes, Mariëtte; Osiyemi, Olayemi; Hardy, Hélène; Bertz, Richard; McGrath, Donnie

    2013-01-01

    Abstract A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia. PMID:23782005

  9. Clinical and pharmacogenetic factors affecting neonatal bilirubinemia following atazanavir treatment of mothers during pregnancy.

    PubMed

    Eley, Timothy; Huang, Shu-Pang; Conradie, Francesca; Zorrilla, Carmen D; Josipovic, Deirdre; Botes, Mariëtte; Osiyemi, Olayemi; Hardy, Hélène; Bertz, Richard; McGrath, Donnie

    2013-10-01

    A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia. PMID:23782005

  10. Exercise testing in the clinical management of patients affected by pulmonary arterial hypertension.

    PubMed

    Paolillo, Stefania; Farina, Stefania; Bussotti, Maurizio; Iorio, Annamaria; PerroneFilardi, Pasquale; Piepolil, Massimo F; Agostoni, Piergiuseppe

    2012-10-01

    Patients affected by pulmonary arterial hypertension (PAH) show a reduced exercise tolerance with early occurrence of dyspnoea and fatigue. The origin of functional capacity limitation is multifactorial and several mechanisms have been proposed, including right heart failure, which leads to a limited increase in cardiac output during exercise, and hyperventilation with a reduced perfusion of properly ventilated alveoli. In addition, abnormalities in arterial blood gases are observed, with the occurrence of hypoxemia and hypocapnia, related to an abnormal ventilation/perfusion match, gas diffusion abnormalities, low mixed venous oxygen saturation and to the development of intra- and extra-pulmonary right-to-left shunts. At present, the 6-minute walking test is the most used method to assess exercise tolerance in PAH; it is also useful to monitor the response to therapy and provides prognostic information. However, the assessment of functional capacity by cardiopulmonary exercise test (CPET) seems to be more complete, because CPET allows for discrimination between the metabolic, cardiovascular and pulmonary components of exercise limitation. Moreover, CPET estimates the severity of disease and assesses patients' prognosis and response to therapy. In PAH, a typical CPET-response is observed, characterized by a severe reduction in peak VO2, work rate, O2 pulse and anaerobic threshold and by a marked increase in VE/VCO2 slope and in the dead space to tidal volume ratio. However, the use of CPET should be limited to experienced centres. This review will focus on resting lung function and exercise tolerance tests, showing that CPET can provide the physiological explanation of functional limitation in PAH. PMID:23126000

  11. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

    Plasma utilization has increased over the past 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 after 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 and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or 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

  12. Heart-type fatty acid binding protein and high-sensitivity troponin T are myocardial damage markers that could predict adverse clinical outcomes in patients with peripheral artery disease

    PubMed Central

    Otaki, Yoichiro; Takahashi, Hiroki; Watanabe, Tetsu; Yamaura, Gensai; Funayama, Akira; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Kubota, Isao

    2015-01-01

    Background Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators of future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD. Methods and results We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow-up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H-FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan–Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors. Conclusion The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients. PMID:26673681

  13. Altered plasma pharmacokinetics of ceftiofur hydrochloride in cows affected with severe clinical mastitis.

    PubMed

    Gorden, P J; Kleinhenz, M D; Wulf, L W; KuKanich, B; Lee, C J; Wang, C; Coetzee, J F

    2016-01-01

    Mastitis is a frequent problem among dairy cows, reducing milk yield and increasing cull rates. Systemic therapy with the cephalosporin antimicrobial ceftiofur hydrochloride (CEF) may improve therapeutic outcomes, but the incidence of CEF violative residues has increased annually since 2011. One potential explanation is that disease status may alter the pharmacokinetics (PK) of CEF. To test this hypothesis, we compared the plasma PK of CEF in healthy cows with those with severe endotoxic mastitis. Eight cows with naturally occurring mastitis and 8 clinically healthy cows were treated with 2.2 mg of CEF per kilogram of body weight once daily for 5d via the intramuscular route. Blood was collected at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 8, 16, and 24h after the first CEF administration and every 8h thereafter until 120 h after the final dose. Plasma samples were analyzed for CEF concentrations using liquid chromatography coupled with mass spectrometry. With the exception of time 0, CEF was detected at all time points. The disease group had a significantly higher plasma CEF concentration at t=3h after the first injection and a significantly lower plasma concentration from 40 to 152 h following the first injection, with the exception of the t=64 h time point. Data following the first injection (time 0-24 h) were fit to a single-dose, noncompartmental PK model. This model indicated that the disease group had a shorter plasma half-life. A multidose, noncompartmental model was used to determine steady-state PK. Compared with control cows, the disease group had an initially higher peak concentration and a higher volume of distribution and drug clearance rates. The disease group also had a lower area under the curve per dosing interval, steady-state concentration maximum, and dose-adjusted peak steady-state concentration. All other PK parameters were not different between the 2 groups. Altered PK, as suggested by this trial, may contribute to an increased risk for the

  14. Evaluation of factors affecting mortality in Fournier’s Gangrene: Retrospective clinical study of sixteen cases

    PubMed Central

    Oymacı, Erkan; Coşkun, Ali; Yakan, Savaş; Erkan, Nazif; Uçar, Ahmet Deniz; Yıldırım, Mehmet

    2014-01-01

    Objective: Fournier’s gangrene is a progressive, necrotizing fasciitis due to synergistic infection of the perineum and external genitalia that is associated with high mortality and morbidity. The purpose of this study is to review the diagnostic and treatment methods that effect mortality in Fournier’s gangrene. Material and Methods: Sixteen patients who were diagnosed and treated at our clinic between 2011 and 2013 due to Fournier’s gangrene were retrospectively analyzed. The surviving and non-surviving patient groups were compared in terms of age, sex, onset time of symptoms, isolated microorganisms, concomitant diseases, Fournier’s gangrene severity index (FGSI), and length of hospital stay. Results: Ten of our cases (62.5%) were male and six (37.5%) were female, with a mean age of 61.2±12.3 (42–73) years. The mortality rate was 18.8% (3 cases). The mean duration of symptoms before admission was 4.31±1.81 (2–8) days. This period was 6.67±1.52 days in patients who succumbed to death, and 3.77±1.42 days in patients who survived (p=0.007). Ten cases (62.5%) had concomitant diabetes mellitus. The most common organism isolated in wound cultures was Escherichia coli (68.7%), and Acinetobacter baumannii, Proteus mirabilis, methicillin-resistant Staphylococcus aureus and Enterococcus spp. in the remaining patients. The mean FGSI of surviving patients was 3.84±1.77, and 7.66±0.57 in fatal cases (p=0.003). The mean length of hospital stay was 25.5 days (2–57) and duration of hospitalization was significantly longer in survivors (p<0.05). Conclusion: The delay in diagnosis and higher FGSI may be responsible for worsening of prognosis and mortality in Fournier’s gangrene. Early diagnosis and determination of the severity of the disease, aggressive surgical debridement and appropriate antimicrobial therapy may improve prognosis. PMID:25931901

  15. Factors affecting the response to the specific treatment of several forms of clinical anestrus in high producing dairy cows.

    PubMed

    López-Gatius, F; Mirzaei, A; Santolaria, P; Bech-Sàbat, G; Nogareda, C; García-Ispierto, I; Hanzen, Ch; Yániz, J L

    2008-06-01

    This study was designed to examine estrous response rates to the therapeutic treatment of clinical anestrus in high producing dairy cows and to identify the factors that could affect these rates. Cows with silent ovulation (Subestrus group), cystic ovarian disease (Cyst group) or ovarian hypofunction (OH group) were given specific treatment for their disorder. Data were derived from 1764 treatments in cows producing a mean of 45.4 kg of milk upon treatment including: 889 subestrous cows, 367 cystic cows and 508 cows with ovarian hypofunction. Cows showing estrus following treatment exhibited a similar pregnancy rate to cows attaining natural estrus used as reference: 33% (337/1006) and 35% (626/1796), respectively. No significant differences in pregnancy rates were observed among the Subestrus, Cyst and OH groups (34% (196/571), 34% (44/130), 32% (97/305), respectively. Based on the odds ratio, an estrous response for all groups was less likely to occur in cows that had suffered previous anestrus, compared to cows that were anestrous for the first time, whereas the likelihood of an estrous response increased in cows treated after 90 days in milk. Our results indicate that previous anestrus and a late stage of lactation can have a negative and positive effect, respectively, on the estrous response to the specific treatment of clinical anestrus shown by high producing dairy cows. Treatment targeted at each type of clinical anestrus can render similar pregnancy rates to those shown by cows in natural estrus. PMID:18359070

  16. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  17. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  18. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  19. Genome scan linkage analysis identifies quantitative trait loci affecting serum clinical-chemical traits in Korean native chicken.

    PubMed

    Seo, Dong-Won; Park, Hee-Bok; Jin, Shil; Cahyadi, Muhammad; Choi, Nuri; Heo, Kang-Nyeong; Jo, Cheorun; Lee, Jun-Heon

    2016-07-01

    Alterations in robustness- and health-related traits lead to physiological changes, such as changes in the serum clinical chemical parameters in individuals. Therefore, clinical-chemical traits can be used as biomarkers to examine the health status of chickens. The aim of the present study was to detect the quantitative trait loci (QTLs) influencing eight clinical-chemical traits (glucose, total protein, creatinine, high-density lipoprotein cholesterol, total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and α-amylase) in an F1 nuclear families comprising 83 F0 founders and 585 F1 progeny of Korean native chickens. Genotypic data on 135 DNA markers representing 26 autosomes have been generated for this resource pedigree. The total length of the map was 2729.4 cM. We used a multipoint variance component linkage approach to identify QTLs for the traits. A significant QTL affecting serum α-amylase levels was identified on chicken chromosome (GGA) 7 [logarithm of odds (LOD) = 3.02, P value = 1.92 × 10(-4)]. Additionally, we detected several suggestive linkage signals for the levels of total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine on GGA 4, 12, 13, and 15. In this study, serum α-amylase levels related significant QTL was mapped on GGA7 and cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine traits related suggestive QTLs were detected on GGA4, 12, 13 and 15, respectively. Further verification and fine mapping of these identified QTLs can provide valuable information for understanding the variations of clinical chemical trait in chickens. PMID:27188424

  20. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands

    PubMed Central

    2014-01-01

    Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of

  1. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  2. Seasonal variation in affective and other clinical symptoms among high-risk families for bipolar disorders in an Arctic population

    PubMed Central

    Pirkola, Sami; Eriksen, Heidi A.; Partonen, Timo; Kieseppä, Tuula; Veijola, Juha; Jääskeläinen, Erika; Mylläri-Figuerola, Eeva-Maija; Salo, Paula M.; Paunio, Tiina

    2015-01-01

    Background In bipolar disorder (BD), seasonality of symptoms is common and disturbances in circadian rhythms have been reported. Objectives We identified high-penetrance families in a geographically restricted area in Northern Fennoscandia and studied the seasonal variation of clinical symptoms among BD subjects and their healthy relatives. Design We explored the clinical characteristics of subjects living in Northern Fennoscandia, with extreme annual variation in daylight. Among known indigenous high-risk families for BD, we compared the affected ones (N=16) with their healthy relatives (N=15), and also included 18 healthy non-related controls from the same geographical area. Seasonal fluctuation in clinical measures was followed up at the 4 most demarcated photoperiodic time points of the annual cycle: around the summer solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder Questionnaire (MDQ)] and morningness–eveningness questionnaire type (MEQ) were registered, whereas in the follow-up, depressive [Beck Depression Inventory (BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol consumption and sleep were recorded. Results Possibly indicative or statistically significant differences in symptoms between the affected subjects and their healthy relatives were the BDI winter (13.3 vs. 2.6, t=−2.51, p=0.022) and spring scores (12.6 vs. 3.2, t=−1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=−2.08, p=0.052) and spring scores (3.8 vs. 0.82, t=−1.97, p=0.063). Scores were higher among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3) at all the time points, and without the notable seasonality which was observed among the healthy relatives. In the overall population, MDQ and MEQ scores had an inverse correlation (−0.384, significant at 0.016), indicating increased lifetime manic behaviour among “the night

  3. Adverse drug reactions in special populations - the elderly.

    PubMed

    Davies, E A; O'Mahony, M S

    2015-10-01

    The International Conference on Harmonization considers older people a 'special population', as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  4. Identifying Adverse Drug Events by Relational Learning

    PubMed Central

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2013-01-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task, related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events. PMID:24955289

  5. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

    The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided. PMID:25535415

  6. The Clinical Significance of Single Features of Borderline Personality Disorder: Anger, Affective Instability, Impulsivity, and Chronic Emptiness in Psychiatric Outpatients.

    PubMed

    Ellison, William D; Rosenstein, Lia; Chelminski, Iwona; Dalrymple, Kristy; Zimmerman, Mark

    2016-04-01

    Although dimensional models of borderline personality disorder (BPD) are consistent with findings showing that minimal levels of pathology are associated with substantial increases in psychosocial impairment, it is still unclear whether different individual BPD criteria are each clinically significant on their own. The current study uses semistructured interview data from 1,870 adults presenting for outpatient psychiatric treatment to investigate whether the BPD criteria of impulsivity, affective instability, emptiness, and anger are each related to psychosocial morbidity when met in the absence of the other eight criteria. Analyses showed that each of these criteria was associated with dysfunction in comparison with a control group meeting zero BPD criteria, but only the emptiness criterion was a marker of impairment on all indices of psychosocial morbidity: suicidality, history of suicide attempts and psychiatric hospitalizations, social and work dysfunction, Axis I comorbidity, and global functioning. Implications for the study of borderline pathology are discussed. PMID:25893552

  7. Resident trainees do not affect patient satisfaction in an outpatient gastroenterology clinic: A prospective study conducted in a Canadian gastroenterology clinic

    PubMed Central

    Brahmania, Mayur; Young, Madison; Muthiah, Chetty; Ilnyckyj, Alexandra; Duerksen, Donald; Moffatt, Dana C

    2015-01-01

    BACKGROUND: There is little literature regarding how a gastroenterology trainee affects a patient’s interpretation of care during outpatient clinic visits. Improving patient satisfaction is desirable and benefits may include enhanced patient compliance as well as providing trainees with areas for improvement. OBJECTIVES: To evaluate patient satisfaction in an outpatient gastroenterology clinic when seen by a trainee and attending physician versus an attending physician alone. The secondary objective was to evaluate physician characteristics that play a role in creating a positive clinical experience. METHODS: A randomized prospective survey study was conducted over an 11-month period (July 2012 to June 2013) at St Boniface Hospital (Winnipeg, Manitoba). Two gastroenterology fellows (postgraduate year 4 and 5) and nine internal medicine residents (postgraduate year 1 to 3) comprised the ‘trainee’ role, while three academic clinicians comprised the ‘attending’ role. Patients included individuals seen for an initial consultation and were >18 years of age. RESULTS: A total of 211 patients comprised the final study group, with 118 in the attending group and 93 in the trainee group. In univariate analysis, patients more often had a very good experience when seen by an attending physician alone versus a trainee and attending physician (73% versus 56%; P=0.016); however, on multivariate analysis, there was no significant difference in patient satisfaction (OR 0.89; P=0.931). Physician factors found to be associated with high patient satisfaction on multivariate analysis included: addressing all patient concerns (OR 27.56; P=0.021); giving the patient a preliminary diagnosis (OR 78.02; P=0.006); and feeling the physician was thorough (OR 72.53; P=0.029). CONCLUSIONS: The present study did not reveal a difference in patient satisfaction if a patient sees an attending physician alone or with a trainee. Moreover, to improve patient satisfaction in a gastroenterology

  8. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group.

    PubMed

    Heinemann, Lutz; Fleming, G Alexander; Petrie, John R; Holl, Reinhard W; Bergenstal, Richard M; Peters, Anne L

    2015-04-01

    Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error, or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held by the manufacturing companies is not currently shared in a sufficiently transparent manner. Public availability of adverse event (AE) reports on the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is potentially a rich source of safety information but is insufficiently utilized due to the current configuration of the system; the comparable database in Europe (European Databank on Medical Devices [EUDAMED]) is not publicly accessible. Many AEs appear to be attributable to human factors and/or user error, but the extent to which manufacturing companies are required by regulators to consider the interactions of users with the technical features of their products is limited. The clinical studies required by regulators prior to marketing are small and over-reliant on bench testing in relation to "predicate" products. Once a pump is available on the market, insufficient data are made publicly available on its long-term use in a real

  9. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting and research needs. A joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group.

    PubMed

    Heinemann, Lutz; Fleming, G Alexander; Petrie, John R; Holl, Reinhard W; Bergenstal, Richard M; Peters, Anne L

    2015-05-01

    Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycaemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycaemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held by the manufacturing companies is not currently shared in a sufficiently transparent manner. Public availability of adverse event (AE) reports on the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is potentially a rich source of safety information but is insufficiently utilised due to the current configuration of the system; the comparable database in Europe (European Databank on Medical Devices, EUDAMED) is not publicly accessible. Many AEs appear to be attributable to human factors and/or user error, but the extent to which manufacturing companies are required by regulators to consider the interactions of users with the technical features of their products is limited. The clinical studies required by regulators prior to marketing are small and over-reliant on bench testing in relation to 'predicate' products. Once a pump is available on the market, insufficient data are made publicly available on its long-term use in a real

  10. Analysis of Pre-Analytic Factors Affecting the Success of Clinical Next-Generation Sequencing of Solid Organ Malignancies

    PubMed Central

    Chen, Hui; Luthra, Rajyalakshmi; Goswami, Rashmi S.; Singh, Rajesh R.; Roy-Chowdhuri, Sinchita

    2015-01-01

    Application of next-generation sequencing (NGS) technology to routine clinical practice has enabled characterization of personalized cancer genomes to identify patients likely to have a response to targeted therapy. The proper selection of tumor sample for downstream NGS based mutational analysis is critical to generate accurate results and to guide therapeutic intervention. However, multiple pre-analytic factors come into play in determining the success of NGS testing. In this review, we discuss pre-analytic requirements for AmpliSeq PCR-based sequencing using Ion Torrent Personal Genome Machine (PGM) (Life Technologies), a NGS sequencing platform that is often used by clinical laboratories for sequencing solid tumors because of its low input DNA requirement from formalin fixed and paraffin embedded tissue. The success of NGS mutational analysis is affected not only by the input DNA quantity but also by several other factors, including the specimen type, the DNA quality, and the tumor cellularity. Here, we review tissue requirements for solid tumor NGS based mutational analysis, including procedure types, tissue types, tumor volume and fraction, decalcification, and treatment effects. PMID:26343728

  11. Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome.

    PubMed

    Braga-Neto, Pedro; Pedroso, José Luiz; Gadelha, Ary; Laureano, Maura Regina; de Souza Noto, Cristiano; Garrido, Griselda Jara; Barsottini, Orlando Graziani Povoas

    2016-08-01

    Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome. PMID:26298474

  12. [Novel oral anticancer drugs: a review of adverse drug reactions, interactions and patient adherence].

    PubMed

    Bartal, Alexandra; Mátrai, Zoltán; Szucs, Attila; Belinszkaja, Galina; Langmár, Zoltán; Rosta, András

    2012-01-15

    Each aspect of oncological care is widely affected by the spread of oral anticancer agents, which raises several questions in terms of safe medication use and patient adherence. Over the past decade targeted therapies have appeared in clinical practice and revolutionized the pharmacological treatment of malignancies. Regular patient - doctor visits and proper patient education is crucial in order to comply with the therapy previously agreed upon with the oncologist, to increase patient adherence, to detect and to treat adverse effects in early stages. Since the information on the new medicines in Hungarian language is sparse it is the intention of the authors to give an overview of the basic knowledge, patient safety issues, adverse effects and interactions. Official drug information summaries and data on pharmacokinetics, interactions and adverse effects from the literature are reviewed as the basis for this overview. PMID:22217686

  13. [Adverse reaction of pseudoephedrine].

    PubMed

    López Lois, G; Gómez Carrasco, J A; García de Frías, E

    2005-04-01

    We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications. PMID:15826569

  14. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  15. Clinical and methodological confounders in assessing the cerebellar cognitive affective syndrome in adult patients with posterior fossa tumours.

    PubMed

    Omar, Dashne; Ryan, Tracy; Carson, Alan; Bak, Thomas H; Torrens, Lorna; Whittle, Ian

    2014-12-01

    The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS. PMID:24881640

  16. Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

    PubMed Central

    Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

    2013-01-01

    OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

  17. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  18. Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo - Meta-analyses on efficacy and adverse events based on randomized clinical trials.

    PubMed

    Rydén, Lisa; Heibert Arnlind, Marianne; Vitols, Sigurd; Höistad, Malin; Ahlgren, Johan

    2016-04-01

    Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. The literature review was performed according to the principles of the Cochrane Collaboration. The search included common databases up to 2013-01-14. Studies of high or moderate quality were used for grading of evidence. Revman™ software was utilized for meta-analyses of published data. Disease free survival (DFS) and overall survival (OS) were improved with AI monotherapy compared to TAM with high and moderate quality of evidence respectively. Sequenced therapy with AI → TAM (or vice versa) improved DFS compared with TAM with moderate quality of evidence, but did not improve OS (low quality of evidence). However, if only studies on sequenced AI therapy with randomization before endocrine therapy were considered, no improvement of DFS could be found. Fractures are more frequently associated with AI whereas the risk of endometrial cancer and venous thromboembolism are higher with TAM. For cardiovascular events no difference was found between AI (mono- or sequenced therapy) and TAM, whereas sequenced therapy compared with AI had lower risk of cardiovascular events (moderate level of evidence). AIs are superior to TAM as adjuvant hormonal therapy for postmenopausal ER-positive breast cancer. TAM can be considered for individual patients due to the different toxicity profile compared with AI. Cardiovascular events related to AI treatment deserve further attention. PMID:27017249

  19. Hepatic drug metabolism and adverse hepatic drug reactions.

    PubMed

    Schaffner, F

    1975-01-01

    Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin. PMID:171822

  20. [Analgesics in geriatric patients. Adverse side effects and interactions].

    PubMed

    Gosch, Markus

    2015-07-01

    Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions. PMID:26152872

  1. Debridement Arthroplasty for Post-traumatic Stiff Elbow: Intraoperative Factors Affecting the Clinical Results of Surgical Treatment

    PubMed Central

    Cho, Nam Su; Lim, Chan Teak; Yi, Jin Woong

    2009-01-01

    Background This study evaluated the outcomes of debridement arthroplasty for stiff elbows, as well as the factors affecting clinical outcomes after surgical treatment. Methods Eighteen patients with post-traumatic stiff elbows were treated with debridement arthroplasty using a posterior approach. The mean patient age was 33 years (range, 16 to 59 years), and the average follow-up period was 59 months (range, 24 to 141 months). The patient's ability to perform activities of daily living, including combing their hair, feeding themselves, performing hygiene, and putting on shirt and shoes, were evaluated using the Mayo Elbow Performance Score. Results At the last follow-up, 16 elbows had painless motion. Two patients continued to complain of mild intermittent pain. The flexion and extension improved to 121° and 10° after surgery, respectively, indicating an average 34° increase in elbow flexion range and an average 25° increase in elbow extension range (p < 0.001, p < 0.001). The Mayo Elbow Performance Score at the last follow-up was excellent in nine elbows (50%) and good in nine elbows (50%). Conclusions Debridement arthroplasty is a predictable procedure for the treatment of intractable stiff elbow, provided that the elbow is stable and congruous. PMID:19884994

  2. The scientist-practitioner model: how do advances in clinical and cognitive neuroscience affect neuropsychology in the courtroom?

    PubMed

    Wood, Rodger Ll

    2009-01-01

    One of the core tenets of the scientist-practitioner model, slightly modified to make it applicable to modern neuropsychology, is that assessment procedures should be developed, applied, and interpreted in a relevant scientific framework. However, over the last 30 years, the general structure of a neuropsychological assessment has changed little, if at all. It has continued to focus mainly on the assessment of cognitive constructs such as intelligence, memory, attention, and perception. During the same time period, cognitive neuroscience has focused on integrative systems, largely controlled by frontal mechanisms, that allow individuals to utilize cognitive functions in an adaptive way, especially in the context of novel situations or when social stimuli are ambiguous. Consequently, the gulf between cognitive neuroscience and the practice of clinical neuropsychology has grown uncomfortably large. This article attempts to review some of the developments in cognitive and affective neuroscience that are relevant to an evaluation of neuropsychological abilities, especially in a medicolegal context, to determine whether conventional neuropsychological methods can be considered fit for purpose. PMID:19333064

  3. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  4. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate. PMID:3302664

  5. The complement system and adverse pregnancy outcomes.

    PubMed

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

    2015-09-01

    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 fetal 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

  6. Oral adverse reactions due to cinnamon-flavoured chewing gums consumption.

    PubMed

    Calapai, G; Miroddi, M; Mannucci, C; Minciullo, Pl; Gangemi, S

    2014-10-01

    Cinnamon-flavoured products (toothpaste, chewing gum, food, candy and mouthwash) can cause oral adverse reactions; among these, the most common is contact stomatitis (cinnamon contact stomatitis, CCS). Signs and symptoms of contact allergic reactions affecting the oral mucosa can mimic other common oral disorders, making diagnosis difficult. As CCS may be more prevalent than believed and its clinical features can frequently determine misdiagnosis, we reviewed case reports and case series of oral adverse reactions due to cinnamon-containing chewing gums, emphasizing clinical aspects, diagnostic and management procedures. We also proposed an algorithm to perform a diagnosis of CCS as in the previous published literature the diagnostic approach was not based on a harmonized and shared evidence-based procedure. Moreover, as patients can refer to different specialists as dentists, dermatologists and allergists, a multidisciplinary approach is suggested. PMID:24004186

  7. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. PMID:24011493

  8. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues. PMID:27040337

  9. Adverse Reactions to Field Vaccination Against Lumpy Skin Disease in Jordan.

    PubMed

    Abutarbush, S M; Hananeh, W M; Ramadan, W; Al Sheyab, O M; Alnajjar, A R; Al Zoubi, I G; Knowles, N J; Bachanek-Bankowska, K; Tuppurainen, E S M

    2016-04-01

    Lumpy skin disease (LSD) is an emerging disease in the Middle East region and has been recently reported in Jordan. The aim of this study was to investigate the adverse reactions that were reported after vaccine administration. Geographical areas enrolled in the study were free of the disease and away from the outbreak governorate. Sixty-three dairy cattle farms, with a total of 19,539 animals, were included in the study. Of those, 56 farms reported adverse clinical signs after vaccine administration. The duration between vaccine administration and appearance of adverse clinical signs ranged from 1 to 20 days (Mean = 10.3, SD ± 3.9). Clinical signs were similar to those observed with natural cases of lumpy skin disease. These were mainly fever, decreased feed intake, decreased milk production and variable sized cutaneous nodules (a few millimetres to around 2 cm in diameter) that could be seen anywhere on the body (head, neck, trunk, perineum), udder, and/or teats. Nodules were raised and firm initially and then formed dry scabs that could be peeled off the skin. The characteristic deep 'sit fast' appearance was rarely seen and most lesions were superficial. Some cattle had swollen lymph nodes, while a few pregnant animals aborted. The percentage of affected cattle ranged from 0.3 to 25% (Mean = 8, SD ± 5.1). Fever, decreased feed intake, and decreased milk production were seen in 83.9, 85.7, and 94.6% in cattle on the affected farms, respectively. All affected cattle displayed skin nodules over their entire bodies, while 33.9 and 7.1% of the affected farms reported nodular lesions present on the udders and teats, respectively. No mortalities were reported due to vaccine adverse reactions. Duration (course) of clinical signs ranged from 3 to 20 days (Mean = 13.7, SD ± 4.1). Two types of LSD vaccines were used by the farmers in this study. The first one was a sheep pox virus (SPPV) vaccine derived from the RM65 isolate [Jovivac, manufactured by Jordan

  10. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... reports or as the result of a formal clinical trial. (2) As with all reports submitted under paragraph (c... derived from commercial marketing experience, postmarketing clinical investigations, postmarketing... adverse experience obtained from a postmarketing clinical study (whether or not conducted under...

  11. A Randomized Clinical Trial Comparing Affect Regulation and Social Problem-Solving Psychotherapies for Mothers with Victimization-Related PTSD

    ERIC Educational Resources Information Center

    Ford, Julian D.; Steinberg, Karen L.; Zhang, Wanli

    2011-01-01

    Addressing affect dysregulation may provide a complementary alternative or adjunctive approach to the empirically supported trauma memory processing models of cognitive behavior therapy (CBT) for posttraumatic stress disorder (PTSD). A CBT designed to enhance affect regulation without trauma memory processing--trauma affect regulation: guide for…

  12. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. PMID:23836598

  13. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  14. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  15. Internalizing Symptoms and Affective Reactivity in Relation to the Severity of Aggression in Clinically Referred, Behavior-Disordered Children

    ERIC Educational Resources Information Center

    Kolko, David J.; Baumann, Barbara L.; Bukstein, Oscar G.; Brown, Elissa J.

    2007-01-01

    We examined the affective correlates of aggression in children referred to a partial hospitalization program for the treatment of behavior disorders who did not have a mood or anxiety disorder. Parent and teacher ratings of the children's impulsivity, internalizing symptoms, affective reactivity, and aggression were examined for their…

  16. Adverse Events of Auricular Therapy: A Systematic Review

    PubMed Central

    Molassiotis, Alexander; Wang, Tao; Suen, Lorna K. P.

    2014-01-01

    The aim of this study was to systematically evaluate the literature on adverse events associated with auricular therapy (AT). Case reports, case series, surveys, and all types of clinical trials reporting adverse events of AT were included. Relevant articles were mainly retrieved from 13 electronic databases and seven Chinese journals on complementary medicine. AT-related adverse events were reported in 32 randomized controlled trials, five uncontrolled clinical trials, four case reports, and two controlled clinical trials. For auricular acupuncture, the most frequently reported adverse events were tenderness or pain at insertion, dizziness, local discomfort, minor bleeding and nausea, and so forth. For auricular acupressure, local skin irritation and discomfort, mild tenderness or pain, and dizziness were commonly reported. Skin irritation, local discomfort, and pain were detected in auricular electroacupuncture, and minor infection was identified in auricular bloodletting therapy. Most of these events were transient, mild, and tolerable, and no serious adverse events were identified. Our findings provide preliminary evidence that AT is a relatively safe approach. Considering the patient's safety, prospective or retrospective surveys are needed in future research to gather practitioner-reported and patient-reported adverse events on AT, and the quality of adverse events reporting in future AT trials should be improved. PMID:25435890

  17. Glaucoma eye drops adverse skin reactions.

    PubMed

    Cantisani, Carmen; Ambrifi, Marina; Frascani, Federica; Fazia, Gilda; Paolino, Giovanni; Lisi, Roberto; Calvieri, Stefano

    2014-01-01

    The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

  18. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  19. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency.

    PubMed

    Schlotawa, Lars; Ennemann, Eva Charlotte; Radhakrishnan, Karthikeyan; Schmidt, Bernhard; Chakrapani, Anupam; Christen, Hans-Jürgen; Moser, Hugo; Steinmann, Beat; Dierks, Thomas; Gärtner, Jutta

    2011-03-01

    Multiple Sulfatase Deficiency (MSD) is caused by mutations in the sulfatase-modifying factor 1 gene encoding the formylglycine-generating enzyme (FGE). FGE post translationally activates all newly synthesized sulfatases by generating the catalytic residue formylglycine. Impaired FGE function leads to reduced sulfatase activities. Patients display combined clinical symptoms of single sulfatase deficiencies. For ten MSD patients, we determined the clinical phenotype, FGE expression, localization and stability, as well as residual FGE and sulfatase activities. A neonatal, very severe clinical phenotype resulted from a combination of two nonsense mutations leading to almost fully abrogated FGE activity, highly unstable FGE protein and nearly undetectable sulfatase activities. A late infantile mild phenotype resulted from FGE G263V leading to unstable protein but high residual FGE activity. Other missense mutations resulted in a late infantile severe phenotype because of unstable protein with low residual FGE activity. Patients with identical mutations displayed comparable clinical phenotypes. These data confirm the hypothesis that the phenotypic outcome in MSD depends on both residual FGE activity as well as protein stability. Predicting the clinical course in case of molecularly characterized mutations seems feasible, which will be helpful for genetic counseling and developing therapeutic strategies aiming at enhancement of FGE. PMID:21224894

  20. Characterization of Erysipelothrix Species Isolates from Clinically Affected Pigs, Environmental Samples, and Vaccine Strains from Six Recent Swine Erysipelas Outbreaks in the United States ▿

    PubMed Central

    Bender, J. S.; Shen, H. G.; Irwin, C. K.; Schwartz, K. J.; Opriessnig, T.

    2010-01-01

    The aim of this study was to characterize Erysipelothrix sp. isolates from clinically affected pigs and their environment and compare them to the Erysipelothrix sp. vaccines used at the sites. Samples were collected during swine erysipelas outbreaks in vaccinated pigs in six Midwest United States swine operations from 2007 to 2009. Pig tissue samples were collected from 1 to 3 pigs from each site. Environmental samples (manure, feed, central-line water, oral fluids, and swabs collected from walls, feed lines, air inlets, exhaust fans, and nipple drinkers) and live vaccine samples were collected following the isolation of Erysipelothrix spp. from clinically affected pigs. All Erysipelothrix sp. isolates obtained were further characterized by serotyping. Selected isolates were further characterized by PCR assays for genotype (E. rhusiopathiae, E. tonsillarum, Erysipelothrix sp. strain 1, and Erysipelothrix sp. strain 2) and surface protective antigen (spa) type (A, B1, B2, and C). All 26 isolates obtained from affected pigs were E. rhusiopathiae, specifically, serotypes 1a, 1b, 2, and 21. From environmental samples, 56 isolates were obtained and 52/56 were E. rhusiopathiae (serotypes 1a, 1b, 2, 6, 9, 12, and 21), 3/56 were Erysipelothrix sp. strain 1 (serotypes 13 and untypeable), and one was a novel species designated Erysipelothrix sp. strain 3 (serotype untypeable). Four of six vaccines used at the sites were commercially available products and contained live E. rhusiopathiae serotype 1a. Of the remaining two vaccines, one was an autogenous live vaccine and contained live E. rhusiopathiae serotype 2 and one was a commercially produced inactivated vaccine and was described by the manufacturer to contain serotype 2 antigen. All E. rhusiopathiae isolates were positive for spaA. All Erysipelothrix sp. strain 1 isolates and the novel Erysipelothrix sp. strain 3 isolate were negative for all currently known spa types (A, B1, B2, and C). These results indicate that

  1. Knowledge discovery of drug data on the example of adverse reaction prediction

    PubMed Central

    2014-01-01

    Background Antibiotics are the widely prescribed drugs for children and most likely to be related with adverse reactions. Record on adverse reactions and allergies from antibiotics considerably affect the prescription choices. We consider this a biomedical decision-making problem and explore hidden knowledge in survey results on data extracted from a big data pool of health records of children, from the Health Center of Osijek, Eastern Croatia. Results We applied and evaluated a k-means algorithm to the dataset to generate some clusters which have similar features. Our results highlight that some type of antibiotics form different clusters, which insight is most helpful for the clinician to support better decision-making. Conclusions Medical professionals can investigate the clusters which our study revealed, thus gaining useful knowledge and insight into this data for their clinical studies. PMID:25079450

  2. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  3. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

    Concepts applicable to adverse possession of subsurface minerals are generally the same as those that apply to adverse possession of all real estate. However, special requirements must be satisfied in order to perfect title to subsurface minerals by adverse possession, particularly when there has been a severance of the true title between surface and subsurface minerals. In those jurisdictions where senior and junior grants came from the state or commonwealth covering the same or some of the same land and in those areas where descriptions of land were vague or not carefully drawn, adverse possession serves to solidify land and mineral ownership. There may be some public, social, and economic justification in rewarding, with good title, those who take possession and use real estate for its intended use, including the extraction of subsurface minerals. 96 refernces.

  4. Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine circovirus type 2 (PCV2) which can be further subdivide into two main genotypes, PCV2a and PCV2b, is often clinically associated with respiratory signs, failure-to-thrive, and diarrhea. The precise pathogenesis of PCV2, and in particular its involvement in apoptosis, is controversial. The ob...

  5. Singular PCV2a or PCV2b Infection Results in Apoptosis of Hepatocytes in Clinically Affected Gnotobiotic Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Systemic infection with porcine circovirus type 2 (PCV2) is often clinically associated with respiratory signs, failure to thrive and diarrhea [1]. Currently, PCV2 can be further subdivided into two main genotypes, PCV2a and PCV2b which under experimental conditions result in very simi...

  6. Cadec: A corpus of adverse drug event annotations.

    PubMed

    Karimi, Sarvnaz; Metke-Jimenez, Alejandro; Kemp, Madonna; Wang, Chen

    2015-06-01

    CSIRO Adverse Drug Event Corpus (Cadec) is a new rich annotated corpus of medical forum posts on patient-reported Adverse Drug Events (ADEs). The corpus is sourced from posts on social media, and contains text that is largely written in colloquial language and often deviates from formal English grammar and punctuation rules. Annotations contain mentions of concepts such as drugs, adverse effects, symptoms, and diseases linked to their corresponding concepts in controlled vocabularies, i.e., SNOMED Clinical Terms and MedDRA. The quality of the annotations is ensured by annotation guidelines, multi-stage annotations, measuring inter-annotator agreement, and final review of the annotations by a clinical terminologist. This corpus is useful for studies in the area of information extraction, or more generally text mining, from social media to detect possible adverse drug reactions from direct patient reports. The corpus is publicly available at https://data.csiro.au.(1). PMID:25817970

  7. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  8. Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

  9. Adverse Effects of Common Drugs: General Concepts.

    PubMed

    Karpa, Kelly Dowhower; Lewis, Peter R; Felix, Todd Matthew

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  10. Clinical and structural impact of mutations affecting the residue Phe367 of FOXP3 in patients with IPEX syndrome.

    PubMed

    Colobran, Roger; Álvarez de la Campa, Elena; Soler-Palacín, Pere; Martín-Nalda, Andrea; Pujol-Borrell, Ricardo; de la Cruz, Xavier; Martínez-Gallo, Mónica

    2016-02-01

    Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic autoimmune disease characterized by early-onset life-threatening multisystemic autoimmunity. This rare hereditary disorder is caused by loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor, which plays a key role in the differentiation and function of CD4(+)CD25(+) natural regulatory T cells (Tregs), essential for the establishment and maintenance of natural tolerance. We identified a novel mutation in the FOXP3 gene affecting the Phe367 residue of the protein (F367V) in a family with three male siblings affected by IPEX. Two other mutations affecting the FOXP3 Phe367 residue (F367L and F367C) have been described previously. This unique situation of three mutations affecting the same residue in FOXP3 led us to study the molecular impact of these mutations on the structure of FOXP3 protein. Structure analysis showed that Phe367 is involved in a rich interaction network related to both monomer and dimer structure stabilization, and is crucial for FOXP3 regulatory activity. The relevance of this location is confirmed by the results of SIFT and PolyPhen-2 pathogenicity predictions for F367V mutation. In summary, as assessment of the pathogenicity of a novel mutation is crucial to achieve a proper molecular diagnosis, we analysed the impact of mutations affecting the Phe367 residue using a combined approach that provides a mechanistic view of their pathogenic effect. PMID:26748374

  11. Recent Advances in Preventing Adverse Reactions to Transfusion

    PubMed Central

    Rogers, Thomas S; Fung, Mark K; Harm, Sarah K

    2015-01-01

    The spectrum of adverse reactions to blood product transfusion ranges from a benign clinical course to serious morbidity and mortality.  There have been many advances in technologies and transfusion strategies to decrease the risk of adverse reactions. Our aim is to address a few of the advancements in increasing the safety of the blood supply, specifically pathogen reduction technologies, bacterial contamination risk reduction, and transfusion associated acute lung injury risk mitigation strategies. PMID:27081471

  12. Recent Advances in Preventing Adverse Reactions to Transfusion.

    PubMed

    Rogers, Thomas S; Fung, Mark K; Harm, Sarah K

    2015-01-01

    The spectrum of adverse reactions to blood product transfusion ranges from a benign clinical course to serious morbidity and mortality.  There have been many advances in technologies and transfusion strategies to decrease the risk of adverse reactions. Our aim is to address a few of the advancements in increasing the safety of the blood supply, specifically pathogen reduction technologies, bacterial contamination risk reduction, and transfusion associated acute lung injury risk mitigation strategies. PMID:27081471

  13. The science of evaluation of adverse events associated with vaccination.

    PubMed

    Halsey, Neal A

    2002-07-01

    All vaccines cause some adverse events; serious adverse events are rare. Causal associations between a vaccine and an adverse event rarely can be determined by specific tests such as identifying a vaccine agent in the affected tissue of patients. In the absence of such data, epidemiologic studies can be used to determine if the risk of the disorder is increased in vaccinated compared to unvaccinated individuals. Common mistakes include assuming a causal relationship based on a temporal association only or a series of affected patients. Careful studies have demonstrated that many hypothesized causal associations between vaccines and adverse events were not substantiated. False assumptions regarding causality are likely to occur for illnesses without a carefully defined etiology or pathogenesis. PMID:12199617

  14. Peri-operative adverse respiratory events in children.

    PubMed

    von Ungern-Sternberg, B S; Ramgolam, A; Hall, G L; Sly, P D; Habre, W

    2015-04-01

    Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse

  15. Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning.

    PubMed

    Giakoumaki, Stella G; Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C Robert

    2016-01-01

    Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger's psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The "Borderline/Explosive temperament" (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), "Schizotypal/Disorganized character" (low Self-directedness, low Cooperativeness, high Self-transcendence), and "Low Ego Strength/Fragile" profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. PMID:27019787

  16. Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning

    PubMed Central

    Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C. Robert

    2016-01-01

    Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger’s psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The “Borderline/Explosive temperament” (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), “Schizotypal/Disorganized character” (low Self-directedness, low Cooperativeness, high Self-transcendence), and “Low Ego Strength/Fragile” profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. PMID

  17. [Haematological adverse effects caused by psychiatric drugs].

    PubMed

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  18. [Injectable fillers: adverse reactions and their management].

    PubMed

    Rzany, B; Bachmann, F; Nast, A

    2013-02-01

    Injectable fillers are one of the corner stones of aesthetic medicine. In general they are safe to use. However, adverse reactions may occur. These reactions may be acute, subacute or delayed, e.g. after decades. It is important to know these reactions and to be prepared so that they can be adequately treated, in view of the clinical symptoms, the injected material and if applicable other diseases/treatments that might trigger these reactions. Last but not least, all reactions should be reported either to specialized registries or regulatory agencies. Only then we are able to learn more about these reactions and their best possible treatment. PMID:23407758

  19. Adverse events in 50 cats with allergic dermatitis receiving ciclosporin.

    PubMed

    Heinrich, Nicole A; McKeever, Patrick J; Eisenschenk, Melissa C

    2011-12-01

    Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Information about the adverse effects of ciclosporin in cats has been limited to smaller studies and case reports. Adverse effects in dogs are mainly gastrointestinal in nature, but humans can also experience hypertension and altered renal function. The aim of this retrospective case series study was to document the occurrence and clinical appearance of adverse events in cats receiving ciclosporin to treat allergic skin disease. The medical records of 50 cats with allergic dermatitis treated with oral ciclosporin (1.9-7.3 mg/kg/day) were reviewed. Adverse events occurred in 66% (33 cats). Adverse events likely to be associated with ciclosporin included the following: vomiting or diarrhoea within 1-8 weeks of receiving ciclosporin (24%), weight loss (16%), anorexia and subsequent hepatic lipidosis (2%) and gingival hyperplasia (2%). Other adverse events less likely to be associated with ciclosporin therapy included the following: weight gain (14%), dental tartar and gingivitis (10%), otitis (4%), chronic diarrhoea (4%), inflammatory bowel disease with indolent gastrointestinal lymphoma (2%), urinary tract infection (2%), cataract (2%), elevated liver enzymes (2%), hyperthyroidism and renal failure (2%) and transient inappropriate urination (2%). Some cats experienced multiple adverse events. Case-control studies are needed to prove cause and effect of ciclosporin with regard to these adverse events. PMID:21545660

  20. The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in both Healthy and Disease-affected Skin

    PubMed Central

    Del Rosso, James Q.; Levin, Jacqueline

    2011-01-01

    It has been recognized for approximately 50 years that the stratum corneum exhibits biological properties that contribute directly to maintaining and sustaining healthy skin. Continued basic science and clinical research coupled with keen clinical observation has led to more recent recognition and general acceptance that the stratum corneum completes many vital “barrier” tasks, including but not limited to regulating epidermal water content and the magnitude of water loss; mitigating exogenous oxidants that can damage components of skin via an innate antioxidant system; preventing or limiting cutaneous infection via multiple antimicrobial peptides; responding via innate immune mechanisms to “cutaneous invaders” of many origins, including microbes, true allergens, and other antigens; and protecting its neighboring cutaneous cells and structures that lie beneath from damaging effects of ultraviolet radiation. Additionally, specific abnormalities of the stratum corneum are associated with the clinical expression of certain disease states. This article provides a thorough “primer” for the clinician, reviewing the multiple normal homeostatic functions of the stratum corneum and the cutaneous challenges that arise when individual functions of this thin yet very active epidermal layer are compromised by exogenous and/or endogenous factors. PMID:21938268

  1. Clinical evaluation of an antiinflammatory and antioxidant diet effect in 30 dogs affected by chronic otitis externa: preliminary results.

    PubMed

    Di Cerbo, Alessandro; Centenaro, Sara; Beribè, Francesca; Laus, Fulvio; Cerquetella, Matteo; Spaterna, Andrea; Guidetti, Gianandrea; Canello, Sergio; Terrazzano, Giuseppe

    2016-03-01

    The aim of this evaluation study was to assess the possible role of a specific nutraceutical diet in relieving main clinical symptoms of chronic bilateral otitis externa (occlusion of ear canal, erythema, discharge quantity, and odor) in 30 adult dogs. Thirty dogs of different breeds (mean age ± SEM; 6.03 ± 0.15 years and mean weight ± SEM; 32.01 ± 1.17 Kg; 53.3% males, 46.6% females) with evident chronic clinical otitis symptoms were equally divided and randomly assigned to receive either the nutraceutical diet (ND group) or a standard diet (SD group) over a period of 90 days. In all cases a topical pharmacological treatment was given. The nutraceutical diet, also endowed with anti-inflammatory and antioxidant activities, significantly decreased the mean score intensity of all symptoms after 90 days of intervention (P < 0.0001) with the exception of Malassezia pachydermatis infection which was only slightly reduced. Our investigation is one of the few evidence-based results where a commercial nutraceutical diet has been proven effective, in combination with drugs, in relieving otitis externa-related symptoms. This study opens new insights into otitis externa clinical management providing evidence of efficacy of a combined therapy with drugs and a specific nutraceutical diet. PMID:26743397

  2. Parents' Psychiatric Issues May Adversely Affect Some Children

    MedlinePlus

    ... attempted suicide, or who had struggled with antisocial personality disorder or marijuana abuse, were found to face ... and mood disorders, schizophrenia, anxiety, Alzheimer's-related dementia, personality disorders, substance abuse and attempted suicide. Parental histories ...

  3. Patterson-Stevenson-Fontaine syndrome: 30-year follow-up and clinical details of a further affected case

    SciTech Connect

    Wilkie, A.O.M.; Goodacre, T.E.E.

    1997-04-14

    The nosology of the acrofacial dysostoses was reviewed extensively. The Patterson-Stevenson-Fontaine syndrome (MIM 183700) is a rare variant, characterized by variable oligosyndactyly of the feet, unusual ears, deafness, cleft palate and autosomal dominant inheritance. The original description by Patterson and Stevenson concerned an affected father and son; a second family with four affected individuals (some of whom also had learning difficulties) in three generations was described by Fontaine et al. Opitz et al. stated {open_quotes}A follow-up of these patients is strongly urged....{close_quotes} Recently we reviewed the son originally described by Patterson and Stevenson, who is now an adult (case JL). One of his three sons (case AL) has inherited the same condition. 6 refs., 3 figs.

  4. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial

    PubMed Central

    ANTONILLI, MORENA; RAHIMI, HASSAN; VISCONTI, VALERIA; NAPOLETANO, CHIARA; RUSCITO, ILARY; ZIZZARI, ILARIA GRAZIA; CAPONNETTO, SALVATORE; BARCHIESI, GIACOMO; IADAROLA, ROBERTA; PIERELLI, LUCA; RUGHETTI, AURELIA; BELLATI, FILIPPO; PANICI, PIERLUIGI BENEDETTI; NUTI, MARIANNA

    2016-01-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  5. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial.

    PubMed

    Antonilli, Morena; Rahimi, Hassan; Visconti, Valeria; Napoletano, Chiara; Ruscito, Ilary; Zizzari, Ilaria Grazia; Caponnetto, Salvatore; Barchiesi, Giacomo; Iadarola, Roberta; Pierelli, Luca; Rughetti, Aurelia; Bellati, Filippo; Panici, Pierluigi Benedetti; Nuti, Marianna

    2016-04-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  6. The sperm quality and clinical outcomes were not affected by sY152 deletion in Y chromosome for oligozoospermia or azoospermia men after ICSI treatment.

    PubMed

    Zhu, Yuanchang; Wu, Tonghua; Li, Guangui; Yin, Biao; Liu, Hongjie; Wan, Caiyun; Zhang, Hongzhan; Zeng, Yong

    2015-12-01

    Azoospermia factor (AZF) microdeletion plays a key role in the genetic etiology of male infertility. The relationship between sY152 deletion in the AZFc region and clinical outcomes is still unclear. This study was to determine the effects of sY152 deletion on the sperm parameters and clinical outcomes of non-obstructive azoospermia or oligozoospermia men after intracytoplasmic sperm injection (ICSI) treatment. A total of 61 infertile men with AZFc microdeletion of the Y chromosome from January 2008 to December 2012 were recruited in the present study. They were divided into two groups, the sY152 group (n=12) and the AZFc group (n=49), based upon whether they have deleted single sY152 marker or all AZFc markers. Fifty azoospermia or oligozoospermia patients without Y chromosome microdeletion were included as the control group. The sperm quality and clinical data were compared among the three groups. Retrospective cohort-control study was performed. The sperm concentration and motility in sY152 group were better than AZFc group (P<0.05), and were comparable to the control group (P>0.05); the morphology, seminal zinc, seminal fructose and seminal carnitine were similar among the three groups (P>0.05). Patients in both sY152 and AZFc groups had lower fertilization rates (68.40% and 70.63%, respectively) than those in the control group (74.91%), and the differences were statistically significant (P<0.05). No significant differences were found in terms of MII oocyte, high-grade embryo rate, 2PN zygote, number of available embryos and transferred embryos, clinical pregnancy rate, implantation rate, miscarriage rate, multiple pregnancy rate, delivery rate, preterm rate and the male/female ratio among the three groups (P>0.05). Single sY152 deletion might cause a lower fertilization rate, but no adverse effects on sperm quality and clinical outcomes were found. Our study may provide more information for consultation in these patients. PMID:26188156

  7. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  8. Algorithm to assess causality after individual adverse events following immunizations.

    PubMed

    Halsey, Neal A; Edwards, Kathryn M; Dekker, Cornelia L; Klein, Nicola P; Baxter, Roger; Larussa, Philip; Marchant, Colin; Slade, Barbara; Vellozzi, Claudia

    2012-08-24

    Assessing individual reports of adverse events following immunizations (AEFI) can be challenging. Most published reviews are based on expert opinions, but the methods and logic used to arrive at these opinions are neither well described nor understood by many health care providers and scientists. We developed a standardized algorithm to assist in collecting and interpreting data, and to help assess causality after individual AEFI. Key questions that should be asked during the assessment of AEFI include: Is the diagnosis of the AEFI correct? Does clinical or laboratory evidence exist that supports possible causes for the AEFI other than the vaccine in the affected individual? Is there a known causal association between the AEFI and the vaccine? Is there strong evidence against a causal association? Is there a specific laboratory test implicating the vaccine in the pathogenesis? An algorithm can assist with addressing these questions in a standardized, transparent manner which can be tracked and reassessed if additional information becomes available. Examples in this document illustrate the process of using the algorithm to determine causality. As new epidemiologic and clinical data become available, the algorithm and guidelines will need to be modified. Feedback from users of the algorithm will be invaluable in this process. We hope that this algorithm approach can assist with educational efforts to improve the collection of key information on AEFI and provide a platform for teaching about causality assessment. PMID:22507656

  9. An overview on adverse drug reactions to traditional Chinese medicines.

    PubMed

    Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu

    2015-10-01

    The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. PMID:25619530

  10. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  11. Clinical and Echocardiographic Factors Associated With In-Hospital Mortality in Patients With Infective Endocarditis Affecting the Native Tricuspid Valve.

    PubMed

    Mi, Michael Y; Nelson, Sandra B; Weiner, Rory B

    2016-09-01

    Infective endocarditis (IE) is a highly morbid disease, for which most outcomes data come from patients with left-sided valvular lesions. Echocardiographic findings such as vegetation size and prosthetic valve involvement have been identified as important predictors of mortality in left-sided IE, but predictors of outcomes in right-sided IE are less well characterized. Therefore, the aim of this study was to identify clinical and echocardiographic findings predictive of mortality in tricuspid valve (TV) IE. We retrospectively reviewed all echocardiograms showing TV vegetations that were performed at the Massachusetts General Hospital from January 1, 2003, to December 31, 2013. We identified 105 patients who had echocardiographic evidence of TV vegetations and a definite clinical diagnosis of IE based on the modified Duke's criteria but did not have intracardiac device-associated vegetations. Of the 105 patients, 88 survived until discharge. Clinical and echocardiographic factors that positively correlated with in-hospital mortality included age (p = 0.002), immunosuppression status (p = 0.016), blood urea nitrogen level (p = 0.029), Candida causative organism (p = 0.025), left ventricular ejection fraction <40% (p = 0.027), right ventricular (RV) systolic dysfunction (p = 0.009), and estimated RV systolic pressure >40 mm Hg (p = 0.040). Of these factors, immunosuppression status, blood urea nitrogen level, and RV systolic dysfunction were independently associated with increased in-hospital mortality. In conclusion, RV systolic dysfunction may serve as an echocardiographic marker to aid clinicians in identifying high-risk patients with right-sided IE for more aggressive therapy. PMID:27392511

  12. Preferential occurrence of attacks during night sleep and/or upon awakening negatively affects migraine clinical presentation

    PubMed Central

    Gori, Sara; Lucchesi, Cinzia; Baldacci, Filippo; Bonuccelli, Ubaldo

    2015-01-01

    Summary It is well known that migraine attacks can preferentially occur during night sleep and/or upon awakening, however the possible implications of this timing on migraine clinical presentation remain unclear. The aim of this study was to assess the possible consequences of sleep-related migraine (defined as ≥75% of migraine attacks occurring during night sleep and/or upon awakening) on the migraine clinical picture (i.e. migraine-related disability, attack severity, use of symptomatic drugs), subjective sleep quality, excessive daytime sleepiness and fatigue. Two hundred consecutive migraine without aura patients were enrolled; patients with comorbid disorders or chronic medication use were excluded. 39% of the migraineurs included in the study received a diagnosis of sleep-related migraine. The mean frequency of migraine attacks (days per month) did not significantly differ between the patients with and those without sleep-related migraine, whereas migraine-related disability (p<0.0001), mean attack severity (p<0.0001), and monthly intake of symptomatic drugs (p<0.0001) were significantly higher in patients with migraine preferentially occurring at night-time and/or upon awakening. Subjective sleep quality and excessive daytime sleepiness did not differ significantly between the two groups, whereas fatigue was significantly more present in the patients with sleep-related migraine (p=0.0001). These data seem to support the hypothesis that patients with sleep-related migraine represent a subset of individuals with a more severe and disabling clinical presentation of migraine and greater impairment of daily functioning, as suggested by the higher degree of fatigue. Migraineurs with night-time attacks also showed a greater use of symptomatic drugs, possibly related to delayed use of symptomatic treatment. The identification of subtypes of patients with a higher disability risk profile could have crucial implications for individually tailored management of

  13. Does a Physician’s Attitude toward a Patient with Mental Illness Affect Clinical Management of Diabetes? Results from a Mixed-Method Study

    PubMed Central

    Welch, Lisa C; Litman, Heather J; Borba, Christina PC; Vincenzi, Brenda; Henderson, David C

    2015-01-01

    Objective To determine whether physician’s attitudes toward patients with comorbid mental illness affect management of a chronic disease. Data Source A total of 256 primary care physicians interviewed in 2010. Study Design This randomized factorial experiment entailed physicians observing video vignettes of patient-actors with poorly controlled diabetes. Patients were balanced across age, gender, race, and comorbidity (schizophrenia with bizarre or normal affect, depression, eczema). Data Collection Physicians completed structured and semistructured interviews plus chart notes about clinical management and attitudes. Principal Findings Physicians reported more negative attitudes for patients with schizophrenia with bizarre affect (SBA). There were few differences in clinical decisions measured quantitatively or in charting, but qualitative data revealed less trust of patients with SBA as reporters, with more reliance on sources other than engaging the patient in care. Physicians often alerted colleagues about SBA, thereby shaping expectations before interactions occurred. Conclusions Results are consistent with common stereotypes about people with serious mental illness. Vignettes did not include intentional indication of unreliable reporting or danger. Reducing health care disparities requires attention to subtle aspects of managing patients—particularly those with atypical affect—as seemingly slight differences could engender disparate patient experiences over time. PMID:25487069

  14. Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes.

    PubMed

    Desaphy, Jean-François; Gramegna, Gianluca; Altamura, Concetta; Dinardo, Maria Maddalena; Imbrici, Paola; George, Alfred L; Modoni, Anna; Lomonaco, Mauro; Conte Camerino, Diana

    2013-10-01

    Myotonia congenita (MC) is caused by loss-of-function mutations of the muscle ClC-1 chloride channel. Clinical manifestations include the variable association of myotonia and transitory weakness. We recently described a cohort of recessive MC patients showing, at a low rate repetitive nerves stimulation protocol, different values of compound muscle action potential (CMAP) transitory depression, which is considered the neurophysiologic counterpart of transitory weakness. From among this cohort, we studied the chloride currents generated by G190S (associated with pronounced transitory depression), F167L (little or no transitory depression), and A531V (variable transitory depression) hClC-1 mutants in transfected HEK293 cells using patch-clamp. While F167L had no effect on chloride currents, G190S dramatically shifts the voltage dependence of channel activation and A531V reduces channel expression. Such variability in molecular mechanisms observed in the hClC-1 mutants may help to explain the different clinical and neurophysiologic manifestations of each ClCN1 mutation. In addition we examined five different mutations found in compound heterozygosis with F167L, including the novel P558S, and we identified additional molecular defects. Finally, the G190S mutation appeared to impair acetazolamide effects on chloride currents in vitro. PMID:23933576

  15. Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes☆

    PubMed Central

    Desaphy, Jean-François; Gramegna, Gianluca; Altamura, Concetta; Dinardo, Maria Maddalena; Imbrici, Paola; George, Alfred L.; Modoni, Anna; LoMonaco, Mauro; Conte Camerino, Diana

    2013-01-01

    Myotonia congenita (MC) is caused by loss-of-function mutations of the muscle ClC-1 chloride channel. Clinical manifestations include the variable association of myotonia and transitory weakness. We recently described a cohort of recessive MC patients showing, at a low rate repetitive nerves stimulation protocol, different values of compound muscle action potential (CMAP) transitory depression, which is considered the neurophysiologic counterpart of transitory weakness. From among this cohort, we studied the chloride currents generated by G190S (associated with pronounced transitory depression), F167L (little or no transitory depression), and A531V (variable transitory depression) hClC-1 mutants in transfected HEK293 cells using patch-clamp. While F167L had no effect on chloride currents, G190S dramatically shifts the voltage dependence of channel activation and A531V reduces channel expression. Such variability in molecular mechanisms observed in the hClC-1 mutants may help to explain the different clinical and neurophysiologic manifestations of each ClCN1 mutation. In addition we examined five different mutations found in compound heterozygosis with F167L, including the novel P558S, and we identified additional molecular defects. Finally, the G190S mutation appeared to impair acetazolamide effects on chloride currents in vitro. PMID:23933576

  16. Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions

    PubMed Central

    Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

    2015-01-01

    Objective We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Methods Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Results Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). Conclusions We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse

  17. Managing Adverse Events With Immune Checkpoint Agents.

    PubMed

    Dadu, Ramona; Zobniw, Chrystia; Diab, Adi

    2016-01-01

    Immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte antigen 4 and anti programmed cell death 1/programmed cell death 1 ligand antibodies) have shown impressive clinical activity in multiple cancer types. Despite achieving great clinical success, challenges and limitations of these drugs as monotherapy or various combinational strategies include the development of a unique set of immune-related adverse events (irAEs) that can be severe and even fatal. Therefore, identification of patients at risk, prevention, consistent communication between patients and medical team, rapid recognition, and treatment of irAEs are critical in optimizing treatment outcomes. This review focuses on the description of more common irAEs and provides a suggested approach for management of specific irAEs. PMID:27111908

  18. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

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

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  19. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

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

    PubMed Central

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

    2015-01-01

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

  1. Fingolimod-Associated Peripheral Vascular Adverse Effects.

    PubMed

    Russo, Margherita; Guarneri, Claudio; Mazzon, Emanuela; Sessa, Edoardo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-10-01

    Fingolimod is the first oral disease-modifying drug approved for the treatment of multiple sclerosis. The drug is usually well tolerated, and common adverse effects include bradycardia, headache, influenza, diarrhea, back pain, increased liver enzyme levels, and cough. Fingolimod is thought to provide therapeutic benefit by preventing normal lymphocyte egress from lymphoid tissues, thus reducing the infiltration of autoaggressive lymphocytes into the central nervous system. However, because the drug acts on different sphingosine-1-phosphate receptors, it may induce several biological effects by influencing endothelial cell-cell adhesion, angiogenesis, vascular development, and cardiovascular function. We describe a patient with multiple sclerosis who, after 3 weeks of fingolimod administration, developed purplish blotches over the dorsal surface of the distal phalanges of the second and fifth digits and the middle phalanx of the fourth ray, itching, and edema on his left hand, without other evident clinical manifestations. When fingolimod therapy was discontinued, the clinical picture regressed within a few days but reappeared after a rechallenge test. Physicians should be aware of unexpected peripheral vascular adverse effects due to fingolimod use, and patients with vascular-based acropathies should be carefully screened and monitored when taking this drug. PMID:26349949

  2. agr Dysfunction Affects Staphylococcal Cassette Chromosome mec Type-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia

    PubMed Central

    Kang, Chang Kyung; Cho, Jeong Eun; Choi, Yoon Jeong; Jung, Younghee; Kim, Nak-Hyun; Kim, Chung-Jong; Kim, Taek Soo; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Park, Wan Beom; Bang, Ji-Hwan; Kim, Eu Suk; Park, Kyoung Un; Park, Sang Won; Kim, Nam-Joong; Oh, Myoung-don

    2015-01-01

    Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea. PMID:25779574

  3. Demographic and clinical variables affecting mid- to late-life trajectories of plasma ceramide and dihydroceramide species.

    PubMed

    Mielke, Michelle M; Bandaru, Veera Venkata Ratnam; Han, Dingfen; An, Yang; Resnick, Susan M; Ferrucci, Luigi; Haughey, Norman J

    2015-12-01

    It has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age-related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross-sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2-6). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age-related increases compared to men. Ceramides and DHCer were more associated with waist-hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra-individual age- and sex-specific changes occur in synchrony to disease onset and progression. PMID:26193443

  4. Clinical Significance of National Patients Sample Analysis: Factors Affecting Mortality and Length of Stay of Organophosphate and Carbamate Poisoned Patients

    PubMed Central

    Kim, Kyoung-Ho; Lee, Jun Yeob; Yeo, Woon Hyung; Park, Ha Young; Park, Kyung Hye; Cho, Junho; Kim, Hyunjong; Kim, Gun Bea; Park, Deuk Hyun; Yoon, Yoo Sang; Kim, Yang Weon

    2013-01-01

    Objectives This study considered whether there could be a change of mortality and length of stay as a result of inter-hospital transfer, clinical department, and size of hospital for patients with organophosphates and carbamates poisoning via National Patients Sample data of the year 2009, which was obtained from Health Insurance Review and Assessment Services (HIRA). The utility and representativeness of the HIRA data as the source of prognosis analysis in poisoned patients were also evaluated. Methods Organophosphate and carbamate poisoned patients' mortality and length of stay were analyzed in relation to the initial and final treating hospitals and departments, as well as the presence of inter-hospital transfers. Results Among a total of 146 cases, there were 17 mortality cases, and the mean age was 56.8 ± 19.2 years. The median length of stay was 6 days. There was no inter-hospital or inter-departmental difference in length of stay. However, it significantly increased when inter-hospital transfer occurred (transferred 11 days vs. non-transferred 6 days; p = 0.037). Overall mortality rate was 11.6%. The mortality rate significantly increased when inter-hospital transfer occurred (transferred 23.5% vs. non-transferred 7.0%; p = 0.047), but there was no statistical difference in mortality on inter-hospital and inter-department comparison at the initial treating facility. However, at the final treating facility, there was a significant difference between tertiary and general hospitals (5.1% for tertiary hospitals and 17.3% for general hospitals; p = 0.024), although there was no significant inter-departmental difference. Conclusions We demonstrated that hospital, clinical department, length of stay, and mortality could be analyzed using insurance claim data of a specific disease group. Our results also indicated that length of stay and mortality according to inter-hospital transfer could be analyzed, which was previously unknown. PMID:24523992

  5. Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?

    PubMed

    Traish, Abdulmaged M; Melcangi, Roberto Cosimo; Bortolato, Marco; Garcia-Segura, Luis M; Zitzmann, Michael

    2015-09-01

    Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings. PMID

  6. Factors That Affect Quality of Life among People Living with HIV Attending an Urban Clinic in Uganda: A Cohort Study

    PubMed Central

    Mutabazi-Mwesigire, Doris

    2015-01-01

    Introduction With the availability of antiretroviral therapy (ART) and primary general care for people living with HIV (PLHIV) in resource limited settings, PLHIV are living longer, and HIV has been transformed into a chronic illness. People are diagnosed and started on treatment when they are relatively well. Although ART results in clinical improvement, the ultimate goal of treatment is full physical functioning and general well-being, with a focus on quality of life rather than clinical outcomes. However, there has been little research on the relationship of specific factors to quality of life in PLHIV. The objective of this study was to investigate factors associated with quality of life among PLHIV in Uganda receiving basic care and those on ART. Methods We enrolled 1274 patients attending an HIV outpatient clinic into a prospective cohort study. Of these, 640 received ART. All were followed up at 3 and 6 months. Health related quality of life was assessed with the MOS-HIV Health Survey and the Global Person Generated Index (GPGI). Multivariate linear regression and logistic regression with generalized estimating equations were used to examine the relationship of social behavioral and disease factors with Physical Health Summary (PHS) score, Mental Health Summary (MHS) score, and GPGI. Results Among PLHIV receiving basic care, PHS was associated with: sex (p=0.045) - females had lower PHS; age in years at enrollment (p=0.0001) - older patients had lower PHS; and depression (p<0.001) - depressed patients had lower PHS. MHS was only associated with opportunistic infection (p=0.01) - presence of an opportunistic infection was associated with lower MHS. For the GPG the associated variables were age (p=0.03) - older patients had lower GPGI; education (p=0.01) – higher education associated with higher GPGI; and depression - patients with depression had a lower GPGI (p<0.001). Among patients on ART, PHS was associated with: study visit (p=0.01), with increase in

  7. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

    This column reports the theme of adversity addressed in reference to theoretical and metatheoretical considerations for advancing nursing knowledge. The development and content of three classic nursing theories are presented by Neuman representatives, and by theorists King and Roy. Topics for continued dialogue are identified as derived from the interface between philosophy of science issues and these theories. PMID:18378823

  8. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  9. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

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

    1999-01-01

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

  10. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  11. [Clinical and instrumental characteristics of idiopathic hypertrophic cardiomyopathy and dynamics of echocardiographic indices as affected by beta-adrenergic blockaders].

    PubMed

    Barats, S S; Kheĭnonen, I M; Klets, F Kh; Serebrennikov, V A; Lipchenko, A A

    1983-10-01

    Clinical investigation of 31 patients with idiopathic hypertrophic subaortal stenosis (IHSS) and idiopathic hypertrophic nonobstructive cardiomyopathy (IHNCMP) comprised electro- and phonocardiography, roentgenologic examination and echocardiography. The disease was latent in 3 patients, and ischemic heart disease or rheumatic heart lesion had been diagnosed prior to echocardiography in 26. Asymmetrical hypertrophy and hypokinesia of the upper third of the ventricular septum, narrowed left-ventricular cavity and septum-wise systolic movement of the anterior mitral cusp were findings common to all IHSS patients. The ventricular septum/left-ventricular posterior wall thickness ratio was elevated (1.42 +/- 0.06). In IHNCMP patients, this ratio was within normal range. The results of an acute pharmacologic test with 10 mg intravenous obsidan given to 10 IHSS patients suggested that the obstruction of left-ventricular outflow pathway was somewhat reduced. Prolonged (2 months to 3 years) obsidan treatment was given to 25 patients and was associated with positive effect in terms of improved subjective manifestations of the disease. However, echocardiographic patterns only showed moderate improvement in 9 of the 13 patients who had completed 1-3 years' treatment course. PMID:6139501

  12. Critical evaluation of the use of cell cultures for inclusion in clinical trials of patients affected by collagen VI myopathies.

    PubMed

    Sabatelli, P; Palma, E; Angelin, A; Squarzoni, S; Urciuolo, A; Pellegrini, C; Tiepolo, T; Bonaldo, P; Gualandi, F; Merlini, L; Bernardi, P; Maraldi, N M

    2012-07-01

    Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1(-/-) mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established. PMID:21953374

  13. [Do clinical guidelines and economic restrictions on health care affect the criminal liability of health care professionals?].

    PubMed

    Erlinger, Rainer

    2004-05-01

    Criminal liability in connection with clinical guidelines relates to several different aspects: (1) It refers to the guideline authors' liability under criminal law in the case of faulty guidelines. (2) Guidelines do not constitute legally binding rules. They can only contribute to determining the standard for medical specialists. (3) There can and must not be any reversal in the burden of proof with criminal proceedings. (4) In case of a deviation from guidelines and a related breach of duty, the subjective aspect of negligence (i.e. the recognizability of danger) can often be inferred from the knowledge of the respective guideline that we can reasonably expect of the physician. (5) No physician who has adhered to the guidelines can regularly be accused of (subjective) negligence. (6) Problems may be encountered in cases where the topic in question has not been covered, but only peripherally touched upon by guidelines. For the sake of uniformity in our legal system, the individual physician must not be held criminally responsible for the lack of economic means. Possible solutions include: (1) relating the standard to the practically instead of the theoretically feasible, (2) investigating to what extent criminal liability may be limited by acceptability and possibility. The complete refusal to provide medical care under inadequate conditions may increase the endangerment of legally protected rights and therefore be unacceptable. Attempts to improve structures towards the standard may be regarded as meeting the requirements under criminal law. PMID:15250392

  14. Spinocerebellar Ataxia: Patient and Health Professional Perspectives on Whether and How Patents Affect Access to Clinical Genetic Testing

    PubMed Central

    Powell, Ashton; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2011-01-01

    Genetic testing for spinocerebellar ataxia (SCA) is used in diagnosis of rare movement disorders. Such testing generally does not affect treatment, but confirmation of mutations in a known gene can confirm diagnosis and end an often years-long quest for the cause of distressing and disabling symptoms. Through interviews and a web forum hosted by the National Ataxia Foundation, patients and health professionals related their experiences with patents’ impact on access to genetic testing for SCA. In the United States, Athena Diagnostics holds either a patent or an exclusive license to a patent in the case of 6 SCA variants (SCA1-3 & 6-8) and two other hereditary ataxias (Friedreich’s Ataxia and Early Onset Ataxia). Athena has enforced its exclusive rights to SCA-related patents by sending cease and desist letters to multiple laboratories offering genetic testing for inherited neurological conditions, including SCA. Roughly half of web forum respondents had decided not to get genetic tests. Price, coverage and reimbursement by insurers and health plans, and fear of genetic discrimination were the main reasons cited for deciding not to get tested. Price was cited as an access concern by the physicians, and as sole US provider, coverage and reimbursement depend on having payment agreements between Athena and payers. In cases where payers do not reimburse, the patient is responsible for payment, although some patients can apply to the voluntary Athena Access and Patient Protection Programs offered by the company. PMID:20393313

  15. Spinocerebellar ataxia: patient and health professional perspectives on whether and how patents affect access to clinical genetic testing.

    PubMed

    Powell, Ashton; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2010-04-01

    Genetic testing for spinocerebellar ataxia is used in diagnosis of rare movement disorders. Such testing generally does not affect treatment, but confirmation of mutations in a known gene can confirm diagnosis and end an often years-long quest for the cause of distressing and disabling symptoms. Through interviews and a web forum hosted by the National Ataxia Foundation, patients and health professionals related their experiences with the effect of patents on access to genetic testing for spinocerebellar ataxia. In the United States, Athena Diagnostics holds either a patent or an exclusive license to a patent in the case of six spinocerebellar ataxia variants (spinocerebellar ataxia 1-3 and 6-8) and two other hereditary ataxias (Friedreich's Ataxia and Early Onset Ataxia). Athena has enforced its exclusive rights to spinocerebellar ataxia-related patents by sending notification letters to multiple laboratories offering genetic testing for inherited neurological conditions, including spinocerebellar ataxia. Roughly half of web forum respondents had decided not to get genetic tests. Price, coverage and reimbursement by insurers and health plans, and fear of genetic discrimination were the main reasons cited for deciding not to get tested. Price was cited as an access concern by the physicians, and as sole US provider, coverage and reimbursement depend on having payment agreements between Athena and payers. In cases in which payers do not reimburse, the patient is responsible for payment, although some patients can apply to the voluntary Athena Access and Patient Protection Plan offered by the company. PMID:20393313

  16. Role of adverse effects in medication nonadherence in bipolar disorder.

    PubMed

    Mago, Rajnish; Borra, Dileep; Mahajan, Rajeev

    2014-01-01

    Nonadherence to medications is common and associated with poor or limited clinical outcomes in the treatment of bipolar disorder. A review of the literature discloses that adverse effects are one of the commonly reported reasons for nonadherence to mood stabilizers by patients with bipolar disorder. Nevertheless, other than such broad summaries, relatively little attention has been given to the role of adverse effects in relation to nonadherence. This review article is the first to consolidate the available data on this topic. Weight gain, perceived cognitive impairment, tremors, and sedation are the adverse effects most likely to lead to nonadherence. Further research is needed to anticipate, identify, manage, and potentially minimize the impact of adverse effects. PMID:25377611

  17. [Frequency of drug adverse reactions among hospitalized patients].

    PubMed

    González Martínez, L

    1995-01-01

    This article describes the frequency of adverse reactions to drugs in a sample of hospitalized patients in the internal medicine ward seen during a year's term. Of 61 medical charts, we found 8 patients with adverse reactions to drugs during their hospital stay and another 4 patients hospitalized due to adverse reactions to drugs. The majority of the adverse reactions were of moderate degree (75%) and were related to drugs of cardiovascular action (58%). The frequency of reactions in hospitalized patients (13%) is comparable with the results obtained from other hospitals. Yet, the real magnitude of the problem is probably greater since the source of information (hospital charts) the totality of the clinical manifestations are not registered. PMID:8581452

  18. [MedDRA and its applications in statistical analysis of adverse events].

    PubMed

    Lu, Meng-jie; Liu, Yu-xiu

    2015-11-01

    Safety assessment in clinical trials is dependent on an in-depth analysis of the adverse events to a great extent. However, there are difficulties in summary classification, data management and statistical analysis of the adverse events because of the different expressions on the same adverse events caused by regional, linguistic, ethnic, cultural and other differences. In order to ensure the normative expressions, it's necessary to standardize the terms in recording the adverse events. MedDRA (medical dictionary for regulatory activities) has been widely recommended and applied in the world as a powerful support for the adverse events reporting in clinical trials. In this paper, the development history, applicable scope, hierarchy structure, encoding term selection and standardized query strategies of the MedDRA is introduced. Furthermore, the practical process of adverse events encoding with MedDRA is proposed. Finally, the framework of statistical analysis about adverse events is discussed. PMID:26911031

  19. Factors affecting integration of midwifery nursing science theory with clinical practice in Vhembe District, Limpopo Province as perceived by professional midwives

    PubMed Central

    Malwela, Thivhulawi; Lebese, Rachel T.

    2016-01-01

    Background Professional midwives have an important role to play in midwifery training to produce a competent midwife. According to the social learning theory, professional midwives act as role models for students. When allocated for clinical learning experiences in the training hospitals, students will have the opportunity to observe the well-trained, skilled, and experienced professional midwives. The whole process will enable students to integrate theory with practice and they will become competent. Aim The aim of this study was to determine the factors affecting integration of midwifery nursing science theory with clinical practice as perceived by midwives. Setting The study was conducted at the training hospitals in Vhembe district of the Limpopo Province, South Africa. These hospitals were: Donald Fraser, Siloam, and Tshidzini. Methods A qualitative explorative, descriptive and contextual design was used. A Non-probability, convenient sampling method was used to select 11 midwives from the following hospitals: Donald Fraser, Siloam, and Tshidzini, in Vhembe district. In-depth individual interviews were conducted. Data were analysed through open coding method. Result One theme and five sub-themes emerged from the analysed data, namely: shortage of midwives, attitudes towards student midwives, reluctance to perform teaching functions, language barriers, and declining midwifery practice standards. Conclusion Shortage of midwives in the clinical areas led to fewer numbers of mentors whom the students could observe and imitate to acquire clinical skills. Some of the midwives were reluctant to teach students. Recommendations were made for both training institutions and hospitals to employ preceptors for students in the clinical practical. PMID:27380847

  20. Virulence-associated traits in avian Escherichia coli: comparison between isolates from colibacillosis-affected and clinically healthy layer flocks.

    PubMed

    Vandekerchove, D; Vandemaele, F; Adriaensen, C; Zaleska, M; Hernalsteens, J-P; De Baets, L; Butaye, P; Van Immerseel, F; Wattiau, P; Laevens, H; Mast, J; Goddeeris, B; Pasmans, F

    2005-06-15

    Colibacillosis appears to be of increasing importance in layer flocks. The aim of this study was to determine characteristics of avian pathogenic Escherichia coli associated with the occurrence of colibacillosis outbreaks at flock level. Forty E. coli strains originating from layers from healthy flocks ('control isolates'), consisting of 25 caecal and 15 extra-intestinal isolates, were compared with 40 strains isolated from layers originating from colibacillosis-affected flocks ('outbreak isolates'), consisting of 20 caecal and 20 extra-intestinal isolates. The examined characteristics were adhesins, invasivity in T84 cell culture, serum resistance, iron uptake, colicin production, and toxinogenicity. The following traits were significantly more often detected in the outbreak isolates than in the control isolates: tsh, iss, iucA, iutA, irp2, fyuA, iroC, cvaC, colicin and colicin V production. A comparison of the extra-intestinal outbreak isolates and the caecal control isolates yielded the same results as when the caecal isolates, extra-intestinal isolates and total number of isolates of the outbreak and the control group were compared. When comparing the caecal and extra-intestinal isolates within the control and within the outbreak group, no significant differences were detected. The O78 and O2 groups showed significant differences with other O-types and NT strains for prevalence of most of the same characteristics. The combination of type 1 fimbriae, tsh, serum resistance, iss, traT, iucA, fyuA, iroC and colicin or colicin V production was significantly more often present in extra-intestinal outbreak isolates than in extra-intestinal control isolates. Only the combination of serum resistance, fyuA and colicin production was present in all outbreak isolates, with a significantly lower prevalence in the control isolates. None of the characteristics or combinations examined were exclusive to the outbreak isolates. PMID:15917135

  1. Paraoxonase 1 Gene Polymorphism Does Not Affect Clopidogrel Response Variability but Is Associated with Clinical Outcome after PCI

    PubMed Central

    Kang, Jeehoon; Jeon, Ki-Hyun; Kang, Si-Hyuck; Han, Jung-Kyu; Lee, Sang Eun; Yang, Han-Mo; Lee, Hae-Young; Kang, Hyun-Jae; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

    2013-01-01

    Background Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation. Methods A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months. Results PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55–87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78–1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients. Conclusion PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C. PMID:23418418

  2. Gonadotropin-releasing hormone agonist for oocyte triggering in endometrial preparation of letrozole stimulation protocols does not affect clinical outcome of frozen-thawed embryo transfer

    PubMed Central

    Huang, Pin-Xiu; Wei, Ji-Hong; Wei, Li-Hong

    2015-01-01

    Objective: This study aims to evaluate the effectiveness of GnRH agonist in comparison with hCG for triggering final oocyte maturation in endometrial preparation of letrozole stimulation protocols for frozen-thawed embryo transfer. Methods: The frozen-thawed embryo transfer cycles (FET) that use the letrozole stimulation protocols for endometrial preparation were divided into two groups according the different method of triggering final oocyte maturation. The serum LH and E2 levels, and the endometrial thickness on the day of triggering, the clinical pregnancy rates, the miscarriage rates and live birth rates were compared. Results: There were no significant differences in the age, the endometrial thickness, the number of embryos transferred between the two groups. The clinical pregnancy rate, abortion rate and live birth rates of the group A were similar compared with the group B, P<0.05. Conclusion: Using GnRH agonist for oocyte triggering in endometrial preparation of letrozole stimulation protocols for frozen-thawed embryo transfer does not affect the clinical outcome compared with hCG under the same luteal phase support. PMID:26770535

  3. Adverse Prenatal, Perinatal and Neonatal Experiences in Children with Anxiety Disorders.

    PubMed

    Johnco, Carly; Lewin, Adam B; Salloum, Alison; Murphy, Tanya K; Crawford, Erika A; Dane, Brittney F; McBride, Nicole M; Storch, Eric A

    2016-04-01

    This study examined the incidence of adverse prenatal, perinatal, and neonatal experiences amongst children with anxiety disorders, and the relationship to clinical symptomology and functional impairment in treatment-seeking children (N = 107) with a primary anxiety disorder. Anxious children had higher rates of reported maternal prescription medication use during pregnancy, maternal smoking and illness during pregnancy and neonatal complications (including neonatal intensive care and feeding issues) compared with population base rates and non-affected children. Almost one-third had early problems with sleep. Developmental problems were common with more than half having at least one area of delay. More than three quarters of anxious children had a first-degree family member with a psychiatric history. There were several associations between neonatal complications and subsequent clinical symptomology, including attention deficit hyperactivity disorder and depressive comorbidity, anxiety severity and functional impairment. Findings suggest higher rates of perinatal complications in anxious children. PMID:26206734

  4. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  5. Negative emotionality and disconstraint influence PTSD symptom course via exposure to new major adverse life events.

    PubMed

    Sadeh, Naomi; Miller, Mark W; Wolf, Erika J; Harkness, Kate L

    2015-04-01

    Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23-68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality over time. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events. PMID:25659969

  6. Negative Emotionality and Disconstraint Influence PTSD Symptom Course via Exposure to New Major Adverse Life Events

    PubMed Central

    Sadeh, Naomi; Miller, Mark W.; Wolf, Erika J.; Harkness, Kate L.

    2015-01-01

    Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23 – 68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality over time. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events. PMID:25659969

  7. Adverse Effects of Tattoos and Piercing on Parent/Patient Confidence in Health Care Providers.

    PubMed

    Johnson, Scarlett C; Doi, Maegan L M; Yamamoto, Loren G

    2016-09-01

    First impressions based on practitioner appearance often form the basis for preliminary assumptions regarding trust, confidence, and competence, especially in situations where patients or family members do not have an established relationship with the physician. Given their growing prevalence, we strove to further investigate whether visible tattoos or piercings on a medical provider affects a patient's perception of the provider's capabilities and their trust in the care that would be provided. A survey using photographs of simulated practitioners was administered to 314 participants split between rural and urban locations. Study volunteers rated tattooed practitioners with lower confidence ratings when compared with nontattooed practitioners and reported greater degrees of discomfort with greater degrees of facial piercing. We concluded that these factors adversely affect the clinical confidence ratings of practitioners, regardless of the gender, age group, or location of participants. PMID:26603585

  8. Evaluating the accuracy of transcribed clinical data.

    PubMed Central

    Wilton, R.; Pennisi, A. J.

    1993-01-01

    This study evaluated the accuracy of data transcribed into a computer-stored record from a handwritten listing of pediatric immunizations. The immunization records of 459 children seen in the UCLA Children's Health Center in March, 1993 were transcribed into a clinical computer system on an ongoing basis. Of these records, 27 (5.9%) were subsequently found to be inaccurate. Reasons for inaccuracy in the transcribed records included incomplete written records, incomplete transcription of written records, and unavailability of immunization records from multiple health-care providers. The utility of a computer-stored clinical record may be adversely affected by unavoidable inaccuracies in transcribed clinical data. PMID:8130478

  9. Six-year trajectories of post-traumatic stress and severe psychological distress symptoms and associations with timing of trauma exposure, ongoing adversity and sense of injustice: a latent transition analysis of a community cohort in conflict-affected Timor-Leste

    PubMed Central

    Rees, S; Steel, Z; Tam, N; Soares, Z; Soares, C; Silove, DM

    2016-01-01

    Objectives To identify the 6-year trajectories of post-traumatic stress symptoms (PTSS) and psychological distress symptoms, and examine for associations with timing of trauma exposure, ongoing adversity and with the sense of injustice in conflict-affected Timor-Leste. Setting A whole-of-household survey was conducted in 2004 and 2010 in Dili, the capital of Timor-Leste. Participants 1022 adults were followed up over 6 years (retention rate 84.5%). Interviews were conducted by field workers applying measures of traumatic events (TEs), ongoing adversity, a sense of injustice, PTS symptoms and psychological distress. Results Latent transition analysis supported a 3-class longitudinal model (psychological distress, comorbid symptoms and low symptoms). We derived 4 composite trajectories comprising recovery (20.8%), a persisting morbidity trajectory (7.2%), an incident trajectory (37.2%) and a low-symptom trajectory (34.7%). Compared with the low-symptom trajectory, the persistent and incident trajectories reported greater stress arising from poverty and family conflict, higher TE exposure for 2 historical periods, and a sense of injustice for 2 historical periods. The persistent trajectory was unique in reporting greater TE exposure in the Indonesian occupation, whereas the incident trajectory reported greater TE exposure during the later internal conflict that occurred between baseline and follow-up. Compared with the low-symptom trajectory, the incident trajectory reported a greater sense of injustice relating to the periods of the Indonesian occupation and independence. The persistent trajectory was characterised by a sense of injustice relating to the internal conflict and contemporary times. The recovery trajectory was characterised by the absence of these risk factors, the only difference from the low-symptom trajectory being that the former reported a sense of injustice for the period surrounding independence. Conclusions Our findings suggest that the timing

  10. Adverse Effects of Common Drugs: Adults.

    PubMed

    Lewis, Peter R; Karpa, Kelly Dowhower; Felix, Todd Matthew

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  11. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  12. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  13. Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma – analyses of cases from two prospective randomized clinical trials

    PubMed Central

    Bernd, Heinz-Wolfram; Ziepert, Marita; Thorns, Christoph; Klapper, Wolfram; Wacker, Hans-Heinrich; Hummel, Michael; Stein, Harald; Hansmann, Martin-Leo; Ott, German; Rosenwald, Andreas; Müller-Hermelink, Hans-Konrad; Barth, Thomas F. E.; Möller, Peter; Cogliatti, Sergio B.; Pfreundschuh, Michael; Schmitz, Norbert; Trümper, Lorenz; Höller, Silvia; Löffler, Markus; Feller, Alfred C.

    2009-01-01

    Background Research on prognostically relevant immunohistochemical markers in diffuse large B-cell lymphomas has mostly been performed on retrospectively collected clinical data. This is also true for immunohistochemical classifiers that are thought to reflect the cell-of-origin subclassification of gene expression studies. In order to obtain deeper insight into the heterogeneous prognosis of diffuse large B-cell lymphomas and to validate a previously published immunohistochemical classifier, we analyzed data from a large set of cases from prospective clinical trials with long-term follow-up. Design and Methods We performed morphological and extensive immunohistochemical analyses in 414 cases of diffuse large B-cell lymphoma from two prospective randomized clinical trials (NHL-B1/B2, Germany). Classification into germinal center and non-germinal center subtypes of B-cell lymphoma was based on the expression pattern of CD10, BCL6, and IRF4. Multivariate analyses were performed adjusting for the factors in the International Prognostic Index. Results Analyzing 20 different epitopes on tissue microarrays, expression of HLA-DR, presence of CD23+ follicular dendritic cell meshworks, and monotypic light chain expression emerged as International Prognostic Index-independent markers of superior overall survival. Immunoblastic morphology was found to be related to poor event-free survival. The non-germinal center subtype, according to the three-epitope classifier (CD10, BCL6, and IRF4) did not have prognostic relevance when adjusted for International Prognostic Index factors (relative risk=1.2, p=0.328 for overall survival; and relative risk=1.1, p=0.644 for event-free survival). Conclusions The previously reported International Prognostic Index-independent prognostic value of stratification into germinal center/non-germinal center B-cell lymphoma using the expression pattern of CD10, BCL6, and IRF4 was not reproducible in our series. However, other markers and the

  14. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  15. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  16. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  17. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management. PMID:26084665

  18. Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

    PubMed Central

    Raphael, Itay; Webb, Johanna; Stuve, Olaf; Haskins, William E.; Forsthuber, Thomas G.

    2015-01-01

    Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) which affects over 2.5 million people worldwide. Although MS has been extensively studied, many challenges still remain in regards to treatment, diagnosis, and prognosis. Typically, prognosis and individual responses to treatment are evaluated by clinical tests such the expanded disability status scale (EDSS), magnetic resonance imaging (MRI), and presence of oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). However, none of these measures correlate strongly with treatment efficacy or disease progression across heterogeneous patient populations and subtypes of MS. Numerous studies over the past decades have attempted to identify sensitive and specific biomarkers for diagnosis, prognosis, and treatment efficacy of MS. The objective of this article is to review and discuss the current literature on body fluid biomarkers in MS, including research on potential biomarker candidates in the areas of microRNA, messenger RNA, lipids, and proteins. PMID:25523168

  19. Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol

    PubMed Central

    Hobson, Sebastian R; Lim, Rebecca; Gardiner, Elizabeth E; Alers, Nicole O; Wallace, Euan M

    2013-01-01

    Introduction Pre-eclampsia is a common pregnancy condition affecting between 3% and 7% of women. Unfortunately, the exact pathophysiology of the disease is unknown and as such there are no effective treatments that exist notwithstanding prompt delivery of the fetus and culprit placenta. As many cases of pre-eclampsia occur in preterm pregnancies, it remains a significant cause of maternal and perinatal morbidity and mortality. Recently, in vitro and animal studies have highlighted the potential role of antioxidants in mitigating the effects of the disease. Melatonin is a naturally occurring antioxidant hormone and provides an excellent safety profile combined with ease of oral administration. We present the protocol for a phase I pilot clinical trial investigating the efficacy and side effects of maternal treatment with oral melatonin in pregnancies affected by preterm pre-eclampsia. Methods and analysis We propose undertaking a single-arm open label clinical trial recruiting 20 women with preterm pre-eclampsia (24+0–35+6 weeks). We will take baseline measurements of maternal and fetal well-being, levels of oxidative stress, ultrasound Doppler studies and other biomarkers of pre-eclampsia. Women will then be given oral melatonin (10 mg) three times daily until delivery. The primary outcome will be time interval between diagnosis and delivery compared to historical controls. Secondary outcomes will compare the baseline measurements previously mentioned with twice-weekly measurements during treatment and then 6 weeks postpartum. Ethics and dissemination Ethical approval has been obtained from Monash Health Human Research Ethics Committee B (HREC 13076B). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ACTRN12613000476730 (ANZCTR). PMID:24056493

  20. Human papillomavirus 16 E2 interacts with neuregulin receptor degradation protein 1 affecting ErbB-3 expression in vitro and in clinical samples of cervical lesions.

    PubMed

    Paolini, Francesca; Curzio, Gianfranca; Melucci, Elisa; Terrenato, Irene; Antoniani, Barbara; Carosi, Mariantonia; Mottolese, Marcella; Vici, Patrizia; Mariani, Luciano; Venuti, Aldo

    2016-05-01

    The ErbB tyrosine kinase receptors play a key role in regulating many cellular functions and human papillomaviruses (HPVs) may interact with transductional pathway of different growth factor receptors. Here, these interactions were analysed in W12 cell line carrying HPV 16 genome and in clinical samples. W12 cells, in which HPV16 becomes integrated during passages, were utilised to detect viral and ErbB family expression at early (W12E) and late passages (W12G). Interestingly, a strong reduction of ErbB-3 expression was observed in W12G. Loss of the E2 and E5 viral genes occurs in W12G and this may affect ErbB-3 receptor expression. E2 and E5 rescue experiments demonstrated that only E2 gene was able to restore ErbB-3 expression. E2 is a transcriptional factor but the expression levels of ErbB3 were unaffected and ErbB-3 promoter did not show any consensus sequence for E2, thus E2 may interact in another way with ErbB3. Indeed, HPV 16 E2 can modulate ErbB-3 by interacting with the ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp-1) that is involved in the regulation of this receptor, via ubiquitination and degradation. E2 co-immunoprecipitated in a complex with Nrdp-1 leading to hypothesise an involvement of this interaction in ErbB-3 regulation. In addition, 90% of the clinical samples with integrated virus and E2 loss showed no or low ErbB-3 positivity, confirming in vitro results. In conclusion, the new discovered interaction of HPV-16 E2 with Nrdp-1 may affect ErbB-3 expression. PMID:26963794

  1. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis

    PubMed Central

    Kobayashi, Tetsuo; Ito, Satoshi; Kobayashi, Daisuke; Shimada, Atsushi; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2016-01-01

    Objectives To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA). Methods In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined. Results After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. Conclusion The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA. PMID:27111223

  2. Adverse events associated with complementary and alternative medicine use in ovarian cancer patients

    PubMed Central

    Sweet, Erin S.; Standish, Leanna J.; Goff, Barbara; Andersen, M. Robyn

    2015-01-01

    Many women with ovarian cancer are choosing to include complementary and alternative medicine (CAM) substances in conjunction with their conventional treatment for ovarian cancer. A 2004 study by Navo et al., found between 44% and 53% of women with ovarian cancer use some form of CAM. Many oncologists express concern about the concomitant use of CAM during conventional treatment, particularly during chemotherapy. Specifically, some providers theorize that the adjunct use of CAM substances may be detrimental to the achievement of therapeutic levels of chemotherapy by inhibiting or inducing cytochrome P450 enzyme activity leading to increases in drug toxicity, under-treatment of disease or other adverse events. Chemotherapeutic agents have complex pharmacological profiles and narrow therapeutic windows and many factors can affect the pharmacodynamics of these drugs. In an effort to ascertain the extent of the potential problem with simultaneous use of CAM with conventional treatment we undertook comprehensive systematic review of published case reports describing CAM-related adverse events among ovarian cancer patients. Study design This article describes a systematic literature review. Methods The Natural Medicines Comprehensive Database (NMCD). PubMed, EMBASE® and the Cochrane Central Register of Controlled Trials (CCTR) were systematically reviewed for research articles pertaining to known CYP mediated CAM-drug interactions; case reports describing adverse events in patients, and clinical trials which examined the effects of herbs and supplements used during cancer treatment. Results Only one case report and one clinical trial were identified which met our inclusion criteria and were relevant to the current investigation. Conclusion Although there are concerns about the potential for adverse events related to concurrent use of CAM substances during conventional treatment we found few case reports and clinical trials in the literature which support this. However

  3. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication. PMID:26914914

  4. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  5. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  6. Clinical outcomes, survivorship and adverse events with mobile-bearings versus fixed-bearings in hip arthroplasty-a prospective comparative cohort study of 143 ADM versus 130 trident cups at 2 to 6-year follow-up.

    PubMed

    Epinette, Jean-Alain

    2015-02-01

    The principle of dual mobility cups, often called "tripolar", has been developed to overcome the problem of instability following primary hip arthroplasty. We prospectively compared two cohorts which differed only by the type of bearings, i.e." mobile bearing hip" (MBH) in a 143-study cohort of ADM cups versus "fixed bearing hip" (FBH) of 130 Trident PSL cups, at a follow-up at 2-6years. The survival rates at 4.13-years, with instability as endpoint was significantly (P=0.0176) in favor of mobile bearings at 100% with no dislocation reported, versus 94.8% with fixed bearings. These mobile bearings, matching both "modern" dual mobility cups and annealed highly crossed polyethylene, would appear to offer at longer follow-up a valuable solution to clinical outcomes in acetabular arthroplasty. PMID:25449593

  7. Cognitive Change across Cognitive-Behavioral and Light Therapy Treatments for Seasonal Affective Disorder: What Accounts for Clinical Status the Next Winter?

    PubMed Central

    Evans, Maggie; Rohan, Kelly J.; Sitnikov, Lilya; Mahon, Jennifer N.; Nillni, Yael I.; Lindsey, Kathryn Tierney; Vacek, Pamela M.

    2013-01-01

    Efficacious treatments for seasonal affective disorder include light therapy and a seasonal affective disorder-tailored form of cognitive-behavioral therapy. Using data from a parent clinical trial, these secondary analyses examined the relationship between cognitive change over treatment with cognitive-behavioral therapy, light therapy, or combination treatment and mood outcomes the next winter. Sixty-nine participants were randomly assigned to 6-weeks of cognitive-behavioral therapy, light therapy, or combination treatment. Cognitive constructs (i.e., dysfunctional attitudes, negative automatic thoughts, and rumination) were assessed at pre- and post-treatment. Dysfunctional attitudes, negative automatic thoughts, and rumination improved over acute treatment, regardless of modality; however, in participants randomized to solo cognitive-behavioral therapy, a greater degree of improvement in dysfunctional attitudes and automatic thoughts was uniquely associated with less severe depressive symptoms the next winter. Change in maladaptive thoughts during acute treatment appears mechanistic of solo cognitive-behavioral therapy’s enduring effects the next winter, but is simply a consequence of diminished depression in light therapy and combination treatment. PMID:24415812

  8. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  9. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  10. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  11. [Recipients adverse reactions: guidance supports].

    PubMed

    Bazin, A

    2010-12-01

    Since 1994, adverse effects of transfusion transmitted to the French haemovigilance network are registered on "e-fit", the database of the French agency for the safety of health products (Afssaps). In order to improve their analysis, guidance supports have been made by Afssaps working groups. Each support deals with a blood transfusion side effect and is composed of five parts including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules of filing the notification form on e-fit. The major characteristics of sheets published or soon-to-be published are presented: transfusion-related acute lung injury, transfusion-transmitted bacterial infection, non-haemolytic febrile reaction, allergic reaction, transfusion-associated circulatory overload, hypotensive transfusion reaction, alloimmunization, erythrocyte incompatibility reaction and hemosiderosis. These new supports give relevant guidelines allowing a better analysis and evaluation of recipients' adverse reactions, particularly their diagnosis, gravity and accountability. They could also initiate studies in European and international haemovigilance and transfusion networks. PMID:21051267

  12. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  13. Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects

    PubMed Central

    Tieri, Paolo; Zhou, XiaoYuan; Zhu, Lisha; Nardini, Christine

    2014-01-01

    Objective: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. Results: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens. PMID:25414848

  14. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  15. Fiber optics in adverse environments

    SciTech Connect

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations.

  16. Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). Recognition, management and avoidance.

    PubMed

    Johnson, A G; Seideman, P; Day, R O

    1993-02-01

    The prevalence and incidence of adverse drug interactions involving nonsteroidal anti-inflammatory drugs (NSAIDs) remains unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and those affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context, and prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to the risk of haemorrhage, and for patients taking high-dose methotrexate due to the dangers of bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified as toxicity may be increased without any improvement in efficacy. Where lithium or anti-hypertensives are coprescribed with NSAIDs, close monitoring is mandatory for lithium toxicity and hypertension, respectively, and aspirin (acetylsalicylic acid) or sulindac are preferred. Phenytoin or oral hypoglycaemic agents may be administered with NSAIDs other than pyrazoles and salicylates provided that patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs, but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterene should be avoided due to the risk of renal failure. High dose aspirin should be replaced by naproxen in patients on valproic acid (sodium valproate) and care is required when corticosteroids are administered to patients

  17. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety. PMID:25078411

  18. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. PMID:27100471

  19. The impact on students of adverse experiences during medical school.

    PubMed

    Wilkinson, Tim J; Gill, Denzil J; Fitzjohn, Julie; Palmer, Claire L; Mulder, Roger T

    2006-03-01

    This study aimed to determine the consequences for, and coping method used by, medical students who experienced adverse experiences during their training. A nationwide questionnaire based census of all current medical students in New Zealand. The response rate was 83% (1384/1660). Two-thirds of students had at least one adverse experience, with humiliation being the most common and having the greatest adverse impact. Unwanted sexual advances, unfair treatment on the basis of gender or race had a lesser impact for most students. Most students took several hours or several days to get over an adverse episode and most commonly they then avoided that person or department. Around one half sought help. Only one-quarter felt it motivated their learning while one-sixth felt it made them consider leaving medical school. The most common perpetrators were senior doctors or nurses. Unwanted sexual advances were most common from other students or from patients. Humiliation is the experience that affected students the most and had a significant adverse effect on learning. There is a disturbing rate of unacceptable practice within medical schools, not all of which is from doctors. PMID:16707293

  20. Integrated Analysis of Genetic and Proteomic Data Identifies Biomarkers Associated with Adverse Events Following Smallpox Vaccination

    EPA Science Inventory

    Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experi...

  1. Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

    PubMed Central

    Miller, Mark D.; Crofton, Kevin M.; Rice, Deborah C.; Zoeller, R. Thomas

    2009-01-01

    Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes. PMID:19654909

  2. Reporting of adverse events for marketed drugs: Need for strengthening safety database

    PubMed Central

    Apte, Aditi Anand

    2016-01-01

    Pharmacovigilance is an evolving discipline in the Indian context. However, there is limited regulatory guidance for adverse event reporting outside the purview of clinical trials. There are number of deficiencies in the framework for adverse event reporting from the perspective of pharma industry, health-care professional and general public due to which adverse events for marketed drugs are highly underreported. This article discusses the need to strengthen national safety database by promoting and mandating reporting of adverse events by all the stakeholders. PMID:27453826

  3. Reporting of adverse events for marketed drugs: Need for strengthening safety database.

    PubMed

    Apte, Aditi Anand

    2016-01-01

    Pharmacovigilance is an evolving discipline in the Indian context. However, there is limited regulatory guidance for adverse event reporting outside the purview of clinical trials. There are number of deficiencies in the framework for adverse event reporting from the perspective of pharma industry, health-care professional and general public due to which adverse events for marketed drugs are highly underreported. This article discusses the need to strengthen national safety database by promoting and mandating reporting of adverse events by all the stakeholders. PMID:27453826

  4. Adverse reactions to new anticonvulsant drugs.

    PubMed

    Wong, I C; Lhatoo, S D

    2000-07-01

    A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to

  5. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... scientific and medical journals either as case reports or as the result of a formal clinical trial. (2) As... experience, postmarketing clinical investigations, postmarketing epidemiological/surveillance studies... adverse drug experiences that occurred in clinical trials if they were previously submitted as part of...

  6. Immune-Related Adverse Events From Immune Checkpoint Inhibitors.

    PubMed

    Marrone, K A; Ying, W; Naidoo, J

    2016-09-01

    Immunotherapy for cancer treatment has come of age, specifically with the use of immune checkpoint antibodies directed against molecules such as CTLA-4, PD-1, and PD-L1. Single-agent and combinatorial approaches utilizing these agents and other immunotherapies that may enhance antitumor effects are under investigation. With increasing clinical use of these agents, an appreciation for their toxicities comes to the fore. Adverse events that occur as a result of the immunologic effects of these therapies are termed "immune-related adverse events" (irAEs), and range in both frequency and severity in reported single-agent and combination studies. Improvements in our understanding of how and why irAEs develop and how to effectively manage them are needed. Herein we provide a state-of-the-art synopsis of the incidence, clinical features, mechanisms, and management of selected irAEs with immune checkpoint inhibitors currently in use. PMID:27170616

  7. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  8. Changing Medicine and Building Community: Maine’s Adverse Childhood Experiences Momentum

    PubMed Central

    Forstadt, Leslie; Cooper, Sally; Andrews, Sue Mackey

    2015-01-01

    Physicians are instrumental in community education, prevention, and intervention for adverse childhood experiences. In Maine, a statewide effort is focusing on education about adverse childhood experiences and ways that communities and physicians can approach childhood adversity. This article describes how education about adversity and resilience can positively change the practice of medicine and related fields. The Maine Resilience Building Network brings together ongoing programs, supports new ventures, and builds on existing resources to increase its impact. It exemplifies the collective impact model by increasing community knowledge, affecting medical practice, and improving lives. PMID:25902346

  9. Childhood Adversity and Cumulative Life Stress: Risk Factors for Cancer-Related Fatigue

    PubMed Central

    Bower, Julienne E.; Crosswell, Alexandra D.; Slavich, George M.

    2013-01-01

    Fatigue is a common symptom in healthy and clinical populations, including cancer survivors. However, risk factors for cancer-related fatigue have not been identified. On the basis of research linking stress with other fatigue-related disorders, we tested the hypothesis that stress exposure during childhood and throughout the life span would be associated with fatigue in breast cancer survivors. Stress exposure was assessed using the Stress and Adversity Inventory, a novel computer-based instrument that assesses for 96 types of acute and chronic stressors that may affect health. Results showed that breast cancer survivors with persistent fatigue reported significantly higher levels of cumulative lifetime stress exposure, including more stressful experiences in childhood and in adulthood, compared to a control group of nonfatigued survivors. These findings identify a novel risk factor for fatigue in the growing population of cancer survivors and suggest targets for treatment. PMID:24377083

  10. Whole body vibration may have immediate adverse effects on the postural sway of stroke patients

    PubMed Central

    Hwang, Ki Jin; Ryu, Young Uk

    2016-01-01

    [Purpose] This study applied whole body vibration (WBV) at different vibration frequencies to chronic stroke patients and examined its immediate effect on their postural sway. [Subjects and Methods] A total of 14 (5 males, 9 females) stroke patients participated. The subjects were randomly assigned to one of the two vibration frequency groups (10 Hz and 40 Hz). Right before and after the application of WBV, the subjects performed quiet standing for 30 seconds, and COP parameters (range, total distance, and mean velocity) were analyzed. [Results] The 10 Hz WBV did not affect the postural sway of stroke patients. The 40 Hz WBV increased postural sway in the ML direction. [Conclusion] The results suggest that WBV application to stroke patients in the clinical field may have adverse effects and therefore caution is necessary. PMID:27064678

  11. Whole body vibration may have immediate adverse effects on the postural sway of stroke patients.

    PubMed

    Hwang, Ki Jin; Ryu, Young Uk

    2016-01-01

    [Purpose] This study applied whole body vibration (WBV) at different vibration frequencies to chronic stroke patients and examined its immediate effect on their postural sway. [Subjects and Methods] A total of 14 (5 males, 9 females) stroke patients participated. The subjects were randomly assigned to one of the two vibration frequency groups (10 Hz and 40 Hz). Right before and after the application of WBV, the subjects performed quiet standing for 30 seconds, and COP parameters (range, total distance, and mean velocity) were analyzed. [Results] The 10 Hz WBV did not affect the postural sway of stroke patients. The 40 Hz WBV increased postural sway in the ML direction. [Conclusion] The results suggest that WBV application to stroke patients in the clinical field may have adverse effects and therefore caution is necessary. PMID:27064678

  12. Adverse reactions to intravenous iodinated contrast media: a primer for radiologists.

    PubMed

    Namasivayam, Saravanan; Kalra, Mannudeep K; Torres, William E; Small, William C

    2006-07-01

    Adverse reactions to intravenous iodinated contrast media may be classified as general and organ-specific, such as contrast-induced nephrotoxicity. General adverse reactions may be subclassified into acute and delayed types. Acute general adverse reactions can range from transient minor reactions to life-threatening severe reactions. Non-ionic contrast media have lower risk of mild and moderate adverse reactions. However, the risk of fatal reactions is similar for ionic and non-ionic contrast media. Adequate preprocedure evaluation should be performed to identify predisposing risk factors. Prompt recognition and treatment of acute adverse reactions is crucial. Risk of contrast induced nephrotoxicity can be reduced by use of non-ionic contrast media, less volume of contrast, and adequate hydration. The radiologist can play a pivotal role by being aware of predisposing factors, clinical presentation, and management of adverse reactions to contrast media. PMID:16688432

  13. A Model of Clinical Alarm Errors in Hospital.

    PubMed

    Busch-Vishniac, Ilene

    2015-01-01

    Although there has been much attention paid recently to clinical alarms, research has primarily focused on particular aspects of the clinical alarm problem, such as how to reduce nuisance alarms. This paper takes a broad view of clinical alarms and develops a model of errors in alarm handling and how they affect patients directly. Based on reports in the literature, I estimate that alarms that should sound by current standards do not sound about 9% of the time. Additionally, about 3% of alarms that are clinically significant are ignored, either intentionally or because they were inaudible. However, these errors produce a very low rate of reported alarm-related deaths and other adverse effects (on the order of a couple adverse effects per 10 million alarm errors). While it is not yet possible to estimate the probabilities of clinical alarms having an adverse impact on patients other than the patient whose alarm is sounding, such indirect adverse effects likely occur at a low level as a result of disruption of staff workflow, creation of a noisy hospital environment, and contribution to communication difficulties. Consideration of alarms should include not only the patient connected to the device that is sounding, but also the impact of the alarm on other patients in the vicinity. PMID:26196919

  14. Application of a Temporal Reasoning Framework Tool in Analysis of Medical Device Adverse Events

    PubMed Central

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

    2011-01-01

    The Clinical Narrative Temporal Relation Ontology (CNTRO)1 project offers a semantic-web based reasoning framework, which represents temporal events and relationships within clinical narrative texts, and infer new knowledge over them. In this paper, the CNTRO reasoning framework is applied to temporal analysis of medical device adverse event files. One specific adverse event was used as a test case: late stent thrombosis. Adverse event narratives were obtained from the Food and Drug Administration’s (FDA) Manufacturing and User Facility Device Experience (MAUDE) database2. 15 adverse event files in which late stent thrombosis was confirmed were randomly selected across multiple drug eluting stent devices. From these files, 81 events and 72 temporal relations were annotated. 73 temporal questions were generated, of which 65 were correctly answered by the CNTRO system. This results in an overall accuracy of 89%. This system should be pursued further to continue assessing its potential benefits in temporal analysis of medical device adverse events. PMID:22195199

  15. No adverse effects of submelt-annealed highly crosslinked polyethylene in cemented cups

    PubMed Central

    2012-01-01

    Background and purpose Highly crosslinked polyethylene (PE) is in standard use worldwide. Differences in the crosslinking procedure may affect the clinical performance. Experimenatal data from retrieved cups have shown free radicals and excessive wear of annealed highly crosslinked PE. We have previously reported low wear and good clinical performance after 6 years with this implant, and now report on the 10-year results. Patients and methods In 8 patients, we measured wear of annealed highly crosslinked PE prospectively with radiostereometry after 10 years. Activity was assessed by UCLA activity score and a specifically designed activity score. Conventional radiographs were evaluated for osteolysis and clinical outcome by the Harris hip score (HHS). Results The mean (95% CI) proximal head penetration for highly crosslinked PE after 10 years was 0.07 (–0.015 to 0.153) mm, and the 3D wear was 0.2 (0.026 to 0.36) mm. Without creep, proximal head penetration was 0.02 (–0.026 to 0.066) mm and for 3D penetration was 0.016 (–0.47 to 0.08) mm. This represents an annual proximal wear of less than 2 µm. All cups were clinically and radiographically stable but showed a tendency of increased rotation after 5 years. Interpretation Wear for annealed highly crosslinked PE is extremely low up to 10 years. Free radicals do not affect mechanical performance or lead to clinically adverse effects. Creep stops after the first 6 months after implantation. Highly crosslinked PE is a true competitor of hard-on-hard bearings. PMID:22248172

  16. Adverse clinical sequelae after skin branding: a case series

    PubMed Central

    2009-01-01

    Introduction Branding refers to a process whereby third degree burns are inflicted on the skin with a hot iron rod or metallic object. Branding employs the phenomenon of "counter irritation," and is widely used by faith healers in developing countries for therapeutic purposes. Some methods, which are very crude and inhuman, carry a large risk of complications. The purpose of this study is to present a series of complications and to familiarize clinicians with this dangerous method of treatment. Case presentation Four Pakistani patients, three male and one female, ranging from 25 to 60 years of age "branded" with a red hot iron rod for various medical reasons presented with severe medical complications to our tertiary care hospital. The mean duration between the procedure and presentation to the hospital was 6 days. At the time of admission, two patients had septic shock, one patient had cavernous sinus thrombosis and one patient had multiple splenic abscesses. All patients received standard care for wound management and systemic infections. Two patients eventually died during the course of treatment. Conclusion Severe complications from branding are troublesome and the potential risks of this treatment outweigh its benefits. Globally, there is a great need for heightened awareness about the dangers of branding among patients and physicians, as this will have an important effect on patients who seek branding for various medical conditions. PMID:19166615

  17. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

    PubMed Central

    Kiff, Cara J.; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

    2012-01-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in ad