Safety of Adrenaline Use in Anaphylaxis: A Multicentre Register.

PubMed

Cardona, Victòria; Ferré-Ybarz, Laia; Guilarte, Mar; Moreno-Pérez, Nuria; Gómez-Galán, Catalina; Alcoceba-Borràs, Eva; Delavalle, Maria Belén; Garriga-Baraut, Teresa

2017-01-01

The use of intramuscular adrenaline to treat anaphylaxis is suboptimal, despite being the first-line treatment recommended by national and international anaphylaxis guidelines. Fear of potentially severe side effects may be one of the underlying factors. The aim of this study was to assess the incidence and severity of adverse side effects after the use of adrenaline in anaphylaxis, as well as potential risk factors. Observational study based on a multicenter online registry of cases of adrenaline administration for suspected anaphylaxis. 277 registered valid cases were included: 138 (51.49%) female, median age 29 years (12-47), and 6 children under 2 years with a median age of 9 months (1-21). Side effects occurred in 58 cases (21.64%), with tremors, palpitations, and anxiety being the most frequent. There was a significant association of developing side effects with older age, higher dose of adrenaline, or use of the intravenous route. Potentially severe adverse effects (high blood pressure, chest discomfort, or ECG alterations) occurred only in 8 cases (2.99%); in these cases, no differences were found according to age or adrenaline dose, but again, intravenous administration was associated with more severe adverse events. This study shows that side effects affect less than 1 in 5 patients who receive adrenaline for an anaphylactic reaction, and are usually mild and transient. Therefore, in an emergency situation such as anaphylaxis, restricting adrenaline administration due to potential adverse effects would, in general, not be justified. © 2017 S. Karger AG, Basel.

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

PubMed

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

2009-03-01

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

Chloramphenicol Toxicity Revisited: A 12-Year-Old Patient With a Brain Abscess

PubMed Central

Wiest, Donald B.; Cochran, Joel B.; Tecklenburg, Fred W.

2012-01-01

Chloramphenicol, a broad-spectrum antibiotic, is rarely used in the United States due to its well-described adverse effects. Because of its limited use, many clinicians are unfamiliar with its indications, spectrum of activity, and potential adverse drug effects. We describe a 12-year-old patient who presented after two craniotomies for a persistent brain abscess complicated by long-term chloramphenicol administration. Findings for this patient were consistent with many of the adverse drug effects associated with chloramphenicol, including elevated chloramphenicol serum concentrations, anemia, thrombocytopenia, reticulocytopenia, and severe metabolic acidosis. Rare manifestations of chloramphenicol toxicity that developed in this patient included neutropenia, visual field changes, and peripheral neuropathy. Chloramphenicol administration was discontinued, and hemodialysis was initiated for severe metabolic acidosis. The patient recovered with severe visual field deficits. Although chloramphenicol is rarely indicated, it remains an effective antibiotic. Healthcare providers should become familiar with the pharmacology, toxicology, and monitoring parameters for appropriate use of this antibiotic. PMID:23118672

Promoting adverse drug reaction reporting: comparison of different approaches

PubMed Central

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

2016-01-01

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report. PMID:27143614

DETERMINING THE CAUSES OF ADVERSE EFFECTS IN NEAR COASTAL ECOSYSTEMS: FROM TOXICITY IDENTIFICATION EVALUATIONS TO WATERSHED DIAGNOTICS

EPA Science Inventory

Several approaches are available for evaluating adverse effects in near coastal ecosystems. These range from performing toxicity tests with individual organisms on water column and sediment samples to conducting macrofaunal compositional analyses on pelagic and benthic communiti...

Adverse Effects of Plant Food Supplements Self-Reported by Consumers in the PlantLIBRA Survey Involving Six European Countries

PubMed Central

Restani, Patrizia; Di Lorenzo, Chiara; Garcia-Alvarez, Alicia; Badea, Mihaela; Ceschi, Alessandro; Egan, Bernadette; Dima, Lorena; Lüde, Saskia; Maggi, Franco M.; Marculescu, Angela; Milà-Villarroel, Raimon; Raats, Monique M.; Ribas-Barba, Lourdes; Uusitalo, Liisa; Serra-Majem, Lluís

2016-01-01

Background The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. Objectives To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. Subjects/Setting From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. Results Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. Conclusions Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals. PMID:26928206

Mitigating adverse event reporting bias in spine surgery.

PubMed

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

2013-08-21

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

Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.

PubMed

Matthews, Eric P

2015-01-01

Although the advent of nonionic low-osmolar contrast agents has reduced the probability of a reaction to radiopaque contrast media derived from tri-iodinated benzoic acid, reactions still occur. Radiologic technologists must understand and know how to manage adverse effects of contrast media. Prompt attention to patients who exhibit the early signs of an adverse reaction can help to ensure the reaction does not progress to become severe or life-threatening.

Industrial Wind Turbine Development and Loss of Social Justice?

ERIC Educational Resources Information Center

Krogh, Carmen M. E.

2011-01-01

This article explores the loss of social justice reported by individuals living in the environs of industrial wind turbines (IWTs). References indicate that some individuals residing in proximity to IWT facilities experience adverse health effects. These adverse health effects are severe enough that some families have abandoned their homes.…

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

2017-03-22

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

A growth curve analysis of the course of dysthymic disorder: the effects of chronic stress and moderation by adverse parent-child relationships and family history.

PubMed

Dougherty, Lea R; Klein, Daniel N; Davila, Joanne

2004-12-01

Using mixed effects models, the authors examined the effects of chronic stress, adverse parent-child relationships, and family history on the 7.5-year course of dysthymic disorder. Participants included 97 outpatients with early-onset dysthymia who were assessed with semistructured interviews at baseline and 3 additional times at 30-month intervals for 7.5 years. Results indicated that higher levels of chronic stress 6 months prior to each follow-up predicted greater depression severity at follow-up, controlling for depression severity at the start of the chronic stress assessment. In addition, adverse parent-child relationships and family history of dysthymic disorder moderated this association. For patients with poorer parent-child relationships, chronic stress was associated with increased depression severity at follow-up, whereas patients with a higher familial loading for dysthymic disorder were less responsive to chronic stress over time. Copyright 2004 APA.

Potential adverse effects of omega-3 Fatty acids in dogs and cats.

PubMed

Lenox, C E; Bauer, J E

2013-01-01

Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Adverse effects of ketoconazole in dogs--a retrospective study.

PubMed

Mayer, Ursula K; Glos, Katharina; Schmid, Matthias; Power, Helen T; Bettenay, Sonya V; Mueller, Ralf S

2008-08-01

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

Anti-epileptic drugs in pediatric traumatic brain injury.

PubMed

Tanaka, Tomoko; Litofsky, N Scott

2016-10-01

Pediatric post-traumatic epilepsy incidence varies depending on reporting mechanism and injury severity; anti-epileptic drug (AEDs) use also varies with lack of quality evidence-based data. Adverse AED effects are not negligible; some may negatively affect functional outcome. This review focuses on clarifying available data. This review discusses seizures associated with traumatic brain injury in children, including seizure incidence, relationship to severity of injury, potential detrimental effects of seizures, potential benefits of AED, adverse effects of AED, new developments in preventing epileptogenesis, and suggested recommendations for patient management. English language papers were identified from PubMed using search terms including but not excluding the following: adverse drug effects, anti-epileptic drugs, children, electroencephalogram, epilepsy, epileptogenesis, head injury, levetiracetam, pediatrics, phenytoin, post-traumatic epilepsy, prevention, prophylaxis, seizures, and traumatic brain injury. Expert commentary: Identification of high-risk patients for post-traumatic seizures is a key goal. Levetiracetam may prevent epileptogenesis, as may other developments.

Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders.

PubMed

Schalinski, Inga; Fischer, Yolanda; Rockstroh, Brigitte

2015-08-30

Accumulating evidence indicates an impact of childhood adversities on the severity and course of mental disorders, whereas this impact on psychotic disorders remains to be specified. Effects of childhood adversities on comorbidity, on symptom severity of the Positive and Negative Syndrome Scale and global functioning across four months (upon admission, 1 and 4 months after initial assessment), as well as the course of illness (measured by the remission rate, number of re-hospitalizations and dropout rate) were evaluated in 62 inpatients with psychotic spectrum disorders. Adverse experiences (of at least 1 type) were reported by 73% of patients. Patients with higher overall level of childhood adversities (n=33) exhibited more co-morbid disorders, especially alcohol/substance abuse and dependency, and higher dropout rates than patients with a lower levels of adverse experiences (n=29), together with higher levels of positive symptoms and symptoms of excitement and disorganization. Emotional and physical neglect were particularly related to symptom severity. Results suggest that psychological stress in childhood affects the symptom severity and, additionally, a more unfavorable course of disorder in patients diagnosed with psychoses. This impact calls for its consideration in diagnostic assessment and psychiatric care. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem.

PubMed

Yen, Cheng-Fang; Yang, Pinchen; Wu, Yu-Yu; Cheng, Chung-Ping

2013-11-01

This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

PubMed

Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma*

PubMed Central

Pinto, Charleston Ribeiro; Almeida, Natalie Rios; Marques, Thamy Santana; Yamamura, Laira Lorena Lima; Costa, Lindemberg Assunção; Souza-Machado, Adelmir

2013-01-01

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here. PMID:24068261

Treatments for iron-deficiency anaemia in pregnancy.

PubMed

Reveiz, Ludovic; Gyte, Gillian Ml; Cuervo, Luis Gabriel; Casasbuenas, Alexandra

2011-10-05

Iron deficiency, the most common cause of anaemia in pregnancy worldwide, can be mild, moderate or severe. Severe anaemia can have very serious consequences for mothers and babies, but there is controversy about whether treating mild or moderate anaemia provides more benefit than harm. To assess the effects of different treatments for anaemia in pregnancy attributed to iron deficiency (defined as haemoglobin less than 11 g/dL or other equivalent parameters) on maternal and neonatal morbidity and mortality. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2011), CENTRAL (2011, Issue 5), PubMed (1966 to June 2011), the International Clinical Trials Registry Platform (ICTRP) (2 May 2011), Health Technology Assessment Program (HTA) (2 May 2011) and LATINREC (Colombia) (2 May 2011). Randomised controlled trials comparing treatments for anaemia in pregnancy attributed to iron deficiency. We identified 23 trials, involving 3.198 women. We assessed their risk of bias. Three further studies identified are awaiting classification. Many of the trials were from low-income countries; they were generally small and frequently methodologically poor. They covered a very wide range of differing drugs, doses and routes of administration, making it difficult to pool data. Oral iron in pregnancy showed a reduction in the incidence of anaemia (risk ratio 0.38, 95% confidence interval 0.26 to 0.55, one trial, 125 women) and better haematological indices than placebo (two trials). It was not possible to assess the effects of treatment by severity of anaemia. A trend was found between dose and reported adverse effects. Most trials reported no clinically relevant outcomes nor adverse effects. Although the intramuscular and intravenous routes produced better haematological indices in women than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects, for example, on venous thrombosis and severe allergic reactions. Daily low-dose iron supplements may be effective at treating anaemia in pregnancy with less gastrointestinal side effects compared with higher doses. Despite the high incidence and burden of disease associated with this condition, there is a paucity of good quality trials assessing clinical maternal and neonatal effects of iron administration in women with anaemia. Daily oral iron treatment improves haematological indices but causes frequent gastrointestinal adverse effects. Parenteral (intramuscular and intravenous) iron enhances haematological response, compared with oral iron, but there are concerns about possible important adverse effects (for intravenous treatment venous thrombosis and allergic reactions and for intramuscular treatment important pain, discolouration and allergic reactions). Large, good quality trials, assessing clinical outcomes (including adverse effects) as well as the effects of treatment by severity of anaemia are required.

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed Central

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.

2017-01-01

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508

[Severe Adverse Pregnancy Outcomes in Placenta Previa and Prior Cesarean Delivery].

PubMed

Zhou, Mi; Chen, Meng; Zhang, Li; He, Guo-Lin; He, Lei; Wei, Qiang; Li, Tao; Liu, Xing-Hui

2017-09-01

To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors. This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes. There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L,and the corresponding odds ratios and 95% confidence intervals were 2.4 (1.5-3.8),3.6 (2.3-5.6) and 2.5 (1.6-3.9),respectively. Pernicious placenta previa,suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L were associated with severe adverse pregnancy outcomes in women with placenta previa and prior cesarean delivery .

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

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

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

Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.

PubMed

Mawson, Anthony

2013-07-15

Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

Herbal remedies and their adverse effects in Tem tribe traditional medicine in Togo.

PubMed

Tchacondo, Tchadjobo; Karou, Simplice D; Batawila, Komlan; Agban, Amegninou; Ouro-Bang'na, Kawiwou; Anani, Kokou T; Gbeassor, Mensavi; de Souza, Comlan

2011-01-01

In Africa, up to 80% of the population relies on herbal concoctions for their primarily health care. In Togo, western Africa, Tem tribe is a population with old knowledge of medicinal plants, however, still very little is known about their medical practices. The present study was conducted to access for the apprehension of adverse effects of traditional remedies by Tem traditional healers (TH). Enquiry was performed by interviews with healers from August to October 2007 in Tchaoudjo prefecture (Togo). The study allowed us to interview 54 TH including 41(75.93%) males and 13(24.07%) females, who cited 102 recipes assumed to have adverse effects. The recipes were used alone to cure several diseases including haemorrhoids (22.55%), female sexual disorders and infertility (21.57%), gastrointestinal disorders (18.63%), and malaria (6.86%). A total of 34 plants belonging to 21 families were cited to be components of the recipes. Euphorbiaceae and Mimosaceae families were the most represented, however, Nauclea latifolia, Khaya senegalensis, Pseudocedrela kotschyi and Xeroderris stuhlmannii were the main components of recipes linked to adverse effects. A total of 20 adverse effects were linked to the administration of theses drugs, and among them; diarrhoea, abdominal pains, polyuria, general weakness and vomiting were the most frequently encountered. These findings were in accordance with several reports of the literature concerning medicinal plants, although they were based on empirical observations. Laboratory screenings are needed to access for the effectiveness as well as the possible toxic effects of the recipes.

Safety profiles of old and new antimicrobials for the treatment of MRSA infections.

PubMed

Bassetti, Matteo; Righi, Elda

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of severe nosocomial and community-acquired infections. Various adverse effects have been associated with compounds that are commonly used in the treatment of MRSA. Prolonged use of high-dose vancomycin has been linked with nephrotoxicity. Linezolid use has been associated with lactic acidosis in regimens longer than 14 days and occurrence of thrombocytopenia in patients with renal impairment. Daptomycin use correlates with reversible and often asymptomatic myopathy. Among new compounds, telavancin has shown increased toxicity compared to vancomycin, especially in patients with severe renal impairment, while a low rate of adverse effects was reported others glycolipopeptides such as dalbavancin and oritavancin and for new cephalosporins. Recently studied oxazolidinones (tedizolid and radezolid) also showed mild adverse effects in Phase 2 and 3 clinical trials. Due to the constant increase in antimicrobial resistance, the use of higher doses and prolonged regimens of antibiotics employed in the treatment of Gram-positive infections has become more common and linked to increased toxicity. Furthermore, new compounds with MRSA activity have been recently approved and will be regularly employed in clinical practice. The knowledge of the adverse effects and risk factors for the development of toxicity associated with anti-MRSA antimicrobials is paramount for the correct use of old and new compounds, especially in the treatment of severe infections.

Effects of solid barriers on dispersion of roadway emissions

EPA Science Inventory

Several studies have found that exposure to traffic-generated air pollution is associated with several adverse health effects. Field studies, laboratory experiments, and numerical simulations indicate that roadside barriers represent a practical method of mitigating the impact of...

Predictors of local adverse effects caused by topical tretinoin cream 0·1% in the Veterans Affairs Topical Tretinoin Chemoprevention trial.

PubMed

Pomerantz, H; Weinstock, M A

2014-09-01

Topical tretinoin is commonly prescribed, but its frequent adverse effects are barriers to use. Predictors of resistance or susceptibility to retinoid irritation are not known. To identify baseline patient characteristics associated with adverse effects of topical tretinoin. This cohort study used data collected from 324 participants in the Veterans Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply tretinoin cream on the face and ears. Univariate and multivariate logistic regression models were used to examine the associations between baseline characteristics and local adverse effects. One hundred and ninety-seven patients (61% of those randomized to tretinoin) reported local adverse effects within 6 months. Clinical signs of severe photodamage at baseline [odds ratio (OR) 0·15, 95% confidence interval (CI) 0·04-0·54] and history of acne (OR 0·46, 95% CI 0·27-0·77) were associated with a decreased risk of adverse effects to tretinoin. The use of other topical medications at enrolment (OR 1·88, 95% CI 1·15-3·08) predicted an increase in adverse effects. In this study population, the common indications of topical tretinoin treatment were associated with lower risks of adverse effects. The concurrent use of other topical medications may worsen irritation caused by tretinoin. © 2014 British Association of Dermatologists.

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

PubMed

Lai, Yi Chun; Yew, Yik Weng

2015-07-01

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

Building a knowledge base of severe adverse drug events based on AERS reporting data using semantic web technologies.

PubMed

Jiang, Guoqian; Wang, Liwei; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

2013-01-01

A semantically coded knowledge base of adverse drug events (ADEs) with severity information is critical for clinical decision support systems and translational research applications. However it remains challenging to measure and identify the severity information of ADEs. The objective of the study is to develop and evaluate a semantic web based approach for building a knowledge base of severe ADEs based on the FDA Adverse Event Reporting System (AERS) reporting data. We utilized a normalized AERS reporting dataset and extracted putative drug-ADE pairs and their associated outcome codes in the domain of cardiac disorders. We validated the drug-ADE associations using ADE datasets from SIDe Effect Resource (SIDER) and the UMLS. We leveraged the Common Terminology Criteria for Adverse Event (CTCAE) grading system and classified the ADEs into the CTCAE in the Web Ontology Language (OWL). We identified and validated 2,444 unique Drug-ADE pairs in the domain of cardiac disorders, of which 760 pairs are in Grade 5, 775 pairs in Grade 4 and 2,196 pairs in Grade 3.

Pharmacogenetics of drugs withdrawn from the market.

PubMed

Zhang, Wei; Roederer, Mary W; Chen, Wang-Qing; Fan, Lan; Zhou, Hong-Hao

2012-01-01

The safety and efficacy of candidate compounds are critical factors during the development of drugs, and most drugs have been withdrawn from the market owing to severe adverse reactions. Individuals/populations with different genetic backgrounds may show significant differences in drug metabolism and efficacy, which can sometimes manifest as severe adverse drug reactions. With an emphasis on the mechanisms underlying abnormal drug effects caused by genetic mutations, pharmacogenetic studies may enhance the safety and effectiveness of drug use, provide more comprehensive delineations of the scope of usage, and change the fates of drugs withdrawn from the market.

Use of Severity Grades to Characterize Histopathologic Changes

EPA Science Inventory

The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should...

Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy.

PubMed

Nathanielsz, Peter W; Ford, Stephen P; Long, Nathan M; Vega, Claudia C; Reyes-Castro, Luis A; Zambrano, Elena

2013-10-01

Maternal obesity is a global epidemic affecting both developed and developing countries. Human and animal studies indicate that maternal obesity adversely programs the development of offspring, predisposing them to chronic diseases later in life. Several mechanisms act together to produce these adverse health effects. There is a consequent need for effective interventions that can be used in the management of human pregnancy to prevent these outcomes. The present review analyzes the dietary and exercise intervention studies performed to date in both altricial and precocial animals, rats and sheep, with the aim of preventing adverse offspring outcomes. The results of these interventions present exciting opportunities to prevent, at least in part, adverse metabolic and other outcomes in obese mothers and their offspring. © 2013 International Life Sciences Institute.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

PubMed

Lüde, Saskia; Vecchio, Sarah; Sinno-Tellier, Sandra; Dopter, Aymeric; Mustonen, Harriet; Vucinic, Slavica; Jonsson, Birgitta; Müller, Dieter; Veras Gimenez Fruchtengarten, Ligia; Hruby, Karl; De Souza Nascimento, Elizabeth; Di Lorenzo, Chiara; Restani, Patrizia; Kupferschmidt, Hugo; Ceschi, Alessandro

2016-06-01

Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Mefloquine use, psychosis, and violence: A retinoid toxicity hypothesis

PubMed Central

Mawson, Anthony R.

2013-01-01

Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects. PMID:23852388

Association between quality of life and self-stigma, insight, and adverse effects of medication in patients with depressive disorders.

PubMed

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

2009-01-01

The aims of this study were to examine whether different domains of quality of life (QOL) are differently affected by depressive disorders by comparing QOL of subjects with and without depressive disorders, and to examine the association of QOL with self-stigma, insight and adverse effects of medication among subjects with depressive disorders. The QOL on the four domains of the WHOQOL-BREF Taiwan version were compared between the 229 subjects with depressive disorders and 106 control subjects. Among the depressive subjects, the association between the four QOL domains and subjects' self-stigma, insight, and adverse effects of medication were examined using multiple regression analyses by controlling for the influence of depression, socio-demographic and clinical characteristics and family function. Depressive subjects had poorer QOL on the physical, psychological and social relationship domains than the non-depressive control group. The depressive subjects who had more severe self-stigma had poorer QOL on all four domains. The depressive subjects who perceived more severe adverse effects from medication had poorer QOL on the physical, psychological and environmental domains. However, insight was not associated with any domain of QOL in patients with depressive disorders. The results of this study demonstrate that different domains of QOL are differently affected by depressive disorders, and that clinicians must consider the negative influences of self-stigma and adverse effects from medication on QOL of subjects with depressive disorders.

Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

PubMed Central

Speyer, Helene; Gluud, Christian; Nordentoft, Merete

2017-01-01

Objectives To assess the benefits and harms of exercise in patients with depression. Design Systematic review Data sources Bibliographical databases were searched until 20 June 2017. Eligibility criteria and outcomes Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention. Results Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes. Conclusions Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes. Systematic review registration The protocol was published in the journal Systematic Reviews: 2015; 4:40. PMID:28928174

Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report.

PubMed

Smith, David; Anderson, David; Degryse, Anne-Dominique; Bol, Carla; Criado, Ana; Ferrara, Alessia; Franco, Nuno Henrique; Gyertyan, Istvan; Orellana, Jose M; Ostergaard, Grete; Varga, Orsolya; Voipio, Hanna-Marja

2018-02-01

Directive 2010/63/EU introduced requirements for the classification of the severity of procedures to be applied during the project authorisation process to use animals in scientific procedures and also to report actual severity experienced by each animal used in such procedures. These requirements offer opportunities during the design, conduct and reporting of procedures to consider the adverse effects of procedures and how these can be reduced to minimize the welfare consequences for the animals. Better recording and reporting of adverse effects should also help in highlighting priorities for refinement of future similar procedures and benchmarking good practice. Reporting of actual severity should help inform the public of the relative severity of different areas of scientific research and, over time, may show trends regarding refinement. Consistency of assignment of severity categories across Member States is a key requirement, particularly if re-use is considered, or the safeguard clause is to be invoked. The examples of severity classification given in Annex VIII are limited in number, and have little descriptive power to aid assignment. Additionally, the examples given often relate to the procedure and do not attempt to assess the outcome, such as adverse effects that may occur. The aim of this report is to deliver guidance on the assignment of severity, both prospectively and at the end of a procedure. A number of animal models, in current use, have been used to illustrate the severity assessment process from inception of the project, through monitoring during the course of the procedure to the final assessment of actual severity at the end of the procedure (Appendix 1).

Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report

PubMed Central

Smith, David; Anderson, David; Degryse, Anne-Dominique; Bol, Carla; Criado, Ana; Ferrara, Alessia; Gyertyan, Istvan; Orellana, Jose M; Ostergaard, Grete; Varga, Orsolya; Voipio, Hanna-Marja

2018-01-01

Directive 2010/63/EU introduced requirements for the classification of the severity of procedures to be applied during the project authorisation process to use animals in scientific procedures and also to report actual severity experienced by each animal used in such procedures. These requirements offer opportunities during the design, conduct and reporting of procedures to consider the adverse effects of procedures and how these can be reduced to minimize the welfare consequences for the animals. Better recording and reporting of adverse effects should also help in highlighting priorities for refinement of future similar procedures and benchmarking good practice. Reporting of actual severity should help inform the public of the relative severity of different areas of scientific research and, over time, may show trends regarding refinement. Consistency of assignment of severity categories across Member States is a key requirement, particularly if re-use is considered, or the safeguard clause is to be invoked. The examples of severity classification given in Annex VIII are limited in number, and have little descriptive power to aid assignment. Additionally, the examples given often relate to the procedure and do not attempt to assess the outcome, such as adverse effects that may occur. The aim of this report is to deliver guidance on the assignment of severity, both prospectively and at the end of a procedure. A number of animal models, in current use, have been used to illustrate the severity assessment process from inception of the project, through monitoring during the course of the procedure to the final assessment of actual severity at the end of the procedure (Appendix 1). PMID:29359995

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

PubMed

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-05-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

Laboratory plasma interactions experiments: Results and implications to future space systems

NASA Technical Reports Server (NTRS)

Leung, Philip

1986-01-01

The experimental results discussed show the significance of the effects caused by spacecraft plasma interactions, in particular the generation of Electromagnetic Interference. As the experimental results show, the magnitude of the adverse effects induced by Plasma Interactions (PI) will be more significant for spacecraft of the next century. Therefore, research is needed to control possible adverse effects. Several techniques to control the selected PI effects are discussed. Tests, in the form of flight experiments, are needed to validate these proposed ideas.

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

PubMed

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2016-10-02

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Patients insist on antibiotics for sinusitis? Here is a good reason to say "no".

PubMed

Schumann, Sarah-Anne; Hickner, John

2008-07-01

Stop prescribing antibiotics for adults with a clinical diagnosis of acute sinusitis, unless the patient has severe symptoms. Antibiotics have little if any positive effects on the severity and duration of symptoms, and they cause adverse effects and create unnecessary expense.

Association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone.

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

The purpose of the present study was to examine the association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone. Thirty outpatients with schizophrenia receiving stable doses of risperidone were comprehensively evaluated for psychopathology, subjective well-being, and adverse drug effects. Subjective well-being was assessed using the Subjective Well-being Under Neuroleptics Scale (SWN). Adverse drug effects were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In correlation analysis controlling for relevant variables, the SWN score had significant negative correlations with the following subscale scores of the LUNSERS: extrapyramidal side effect (EPS) (r = -0.54, P < 0.01), akathisia (r = -0.46, P < 0.05), and autonomic adverse effect (r = -0.44, P < 0.05). The SWN score also had a significant negative correlation with the global severity of EPS as measured by the DIEPSS (r = -0.44, P < 0.05). The results of our study suggest that adverse effects, particularly EPS and akathisia, are significantly associated with subjective well-being, implying the necessity to develop rational strategies to control these variables effectively. The results also suggest that EPS and akathisia continue to be major adverse effects associated with a low level of subjective well-being in patients receiving risperidone. Further studies are required to investigate the multidimensional factors associated with subjective well-being in patients receiving atypical antipsychotics and to determine their relative contributions.

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature.

PubMed

Rasmussen, Keith G; Ritter, Matthew J

2014-12-01

Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.

[Serious systemic adverse events associated with allergen-specific immunotherapy in children with asthma].

PubMed

Dai, Li; Huang, Ying; Wang, Ying; Han, Huan-Li; Li, Qu-Bei; Jiang, Yong-Hui

2014-01-01

To retrospectively assess serious systemic adverse effects of standardized dust-mite vaccine in children with asthma. Medical records of 704 children (5-17 years in age) with asthma between January, 2005 and December, 2011 were reviewed. Serious systemic adverse events following treatment with a standardized dust-mite vaccine in these children were analyzed. A total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3), 318 (94.6%) were not serious (below level 3), and no single case of anaphylactic shock (level 4) was recorded. Systemic adverse events occurred most frequently in the 5 to 11-year age group and in the summer season (from June to August). In the 18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after the vaccine injection, and other major clinical symptoms included cough, wheezing and urticaria. All children with serious systemic adverse effects were given inhaled hormone and atomized short-acting beta agonists, oral antihistamines, intravenous dexamethasone and/or intramuscular adrenaline. After these treatments, the clinical symptoms were significantly relieved. The rate of serious systemic adverse events following allergen-specific immunotherapy is relatively low in children with allergic asthma. Conventional medications are effective in managing these immunotherapy-associated adverse events.

Dredging Research: Information from the Engineer Research and Development Center. Volume 7, Number 1. Corps Education Center a Big Success

DTIC Science & Technology

2004-03-01

likeli- hood of adverse effects. UDMEED contains ecotoxico - logical and reference data relevant to assessing the potential for impacts of concern...The effects data have been translated into ecotoxico - logical endpoints, such as “No Observed Adverse Ecological Effect Level (NOAEL),” “Lethal...ited in an upland situation, several broad taxonomic categories, and various contaminants (e.g., bio- accumulation and plants and metals ; or toxicity

Amiodarone induced pneumonitis and hyperthyroidism: case report.

PubMed

Grabczak, Elzbieta Magdalena; Zielonka, Tadeusz M; Wiwała, Joanna; Bareła, Anna Dagmara; Opuchlik, Andrzej; Potulska, Anna; Ambroziak, Urszula; Chazan, Ryszarda

2008-09-01

Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.

Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.

PubMed

Farr, O M; Ko, B-J; Joung, K E; Zaichenko, L; Usher, N; Tsoukas, M; Thakkar, B; Davis, C R; Crowell, J A; Mantzoros, C S

2015-05-01

There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review.

PubMed

Chellappan, Dinesh Kumar; Leng, Kun Hooi; Jia, Lee Jia; Aziz, Nur Amirah Binti Abdul; Hoong, Wong Chun; Qian, Yap Cheng; Ling, Fam Yi; Wei, Gwee Sing; Ying, Tiong; Chellian, Jestin; Gupta, Gaurav; Dua, Kamal

2018-06-01

The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers. The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review. In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents. Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Modeling U-shaped dose-response curves for manganese using categorical regression.

PubMed

Milton, Brittany; Krewski, Daniel; Mattison, Donald R; Karyakina, Nataliya A; Ramoju, Siva; Shilnikova, Natalia; Birkett, Nicholas; Farrell, Patrick J; McGough, Doreen

2017-01-01

Manganese is an essential nutrient which can cause adverse effects if ingested to excess or in insufficient amounts, leading to a U-shaped exposure-response relationship. Methods have recently been developed to describe such relationships by simultaneously modeling the exposure-response curves for excess and deficiency. These methods incorporate information from studies with diverse adverse health outcomes within the same analysis by assigning severity scores to achieve a common response metric for exposure-response modeling. We aimed to provide an estimate of the optimal dietary intake of manganese to balance adverse effects from deficient or excess intake. We undertook a systematic review of the literature from 1930 to 2013 and extracted information on adverse effects from manganese deficiency and excess to create a database on manganese toxicity following oral exposure. Although data were available for seven different species, only the data from rats was sufficiently comprehensive to support analytical modelling. The toxicological outcomes were standardized on an 18-point severity scale, allowing for a common analysis of all available toxicological data. Logistic regression modelling was used to simultaneously estimate the exposure-response profile for dietary deficiency and excess for manganese and generate a U-shaped exposure-response curve for all outcomes. Data were available on the adverse effects of 6113 rats. The nadir of the U-shaped joint response curve occurred at a manganese intake of 2.70mg/kgbw/day with a 95% confidence interval of 2.51-3.02. The extremes of both deficient and excess intake were associated with a 90% probability of some measurable adverse event. The manganese database supports estimation of optimal intake based on combining information on adverse effects from systematic review of published experiments. There is a need for more studies on humans. Translation of our results from rats to humans will require adjustment for interspecies differences in sensitivity to manganese. Copyright © 2016 Elsevier B.V. All rights reserved.

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

PubMed

Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

2017-05-01

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Postictal ventricular tachycardia after electroconvulsive therapy treatment associated with a lithium-duloxetine combination.

PubMed

Heinz, Boeker; Lorenzo, Perniola; Markus, Risch; Holger, Himmighoffen; Beatrix, Roemer; Erich, Seifritz; Alain, Borgeat

2013-09-01

This report addresses the dilemma of continuing lithium prophylaxis and antidepressant therapy in view of cardiovascular adverse effects under electroconvulsive therapy (ECT) in patients with a long history of recurrent affective disorders. A severely depressed 48-year-old woman who had been treated with lithium for 18 years developed a ventricular tachycardia during ECT. Possible interaction with succinylcholine was taken into account, and rocuronium was used as an alternative muscle relaxant. Electroconvulsive therapy was continued without adverse effects after reduction of lithium and withdrawal from duloxetine. Systemic studies on cardiac adverse effects of serotonin and norepinephrine reuptake inhibitors and serotonin and norepinephrine reuptake inhibitor-lithium combinations during ECT are needed.

Management of common adverse effects in the era of highly active antiretroviral therapy in south east Ethiopia

PubMed Central

Abdella, Sadikalmahdi Hussen; Wabe, Nasir Tajure; Yesuf, Elias Ali

2011-01-01

Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims: The aim of this study was to assess management strategies under taken in patient's experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%), Peripheral neuropathy (36.9%) and Anemia (20.24%). The rate of management was 39.3%. Pyridoxine (36.8%) was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7%) was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients. PMID:22361495

Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.

PubMed

Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng

2012-12-01

Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes].

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos

2011-01-01

To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (versión 10.0,Texas, USA) was used. The results were considered significant at p<0.01. Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

[Side effects of psychotropic medication: Suggestions for clinical practice].

PubMed

Grunze, Anna; Mago, Rajnish; Grunze, Heinz

2017-11-01

Psychotropics are highly effective medications that, however, have adverse drug reactions attached to them. They are indispensable for many patients. How to cope with side effects - watchful waiting, dose reduction, change of medication, addition of an "antidote" and behavioural modifications - depends on their nature, severity and finally the patients wish. This review is meant to aid clinician's and patient's decisions in case of the occurrence of compromising, frequent adverse drug reactions. © Georg Thieme Verlag KG Stuttgart · New York.

European guidelines on managing adverse effects of medication for ADHD

PubMed Central

Banaschewski, T.; Buitelaar, J.; Coghill, D.; Danckaerts, M.; Dittmann, R. W.; Döpfner, M.; Hamilton, R.; Hollis, C.; Holtmann, M.; Hulpke-Wette, M.; Lecendreux, M.; Rosenthal, E.; Rothenberger, A.; Santosh, P.; Sergeant, J.; Simonoff, E.; Sonuga-Barke, E.; Wong, I. C. K.; Zuddas, A.; Steinhausen, H.-C.; Taylor, E.

2010-01-01

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks. PMID:21042924

Cinnamon: A systematic review of adverse events.

PubMed

Hajimonfarednejad, Mahdie; Ostovar, Mohadeseh; Raee, Mohammad Javad; Hashempur, Mohammad Hashem; Mayer, Johannes Gottfried; Heydari, Mojtaba

2018-04-05

Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

Patient compliance with drug therapy in schizophrenia. Economic and clinical issues.

PubMed

Lindström, E; Bingefors, K

2000-08-01

The effectiveness of drug treatment in clinical practice is considerably lower than the efficacy shown in controlled studies. The lower effectiveness in practice presumably leads to lower cost effectiveness of drug treatment in real-life situations compared with that demonstrated by studies based on results from controlled trials. Improved cost effectiveness in routine clinical practice would be a significant advantage in the treatment of schizophrenia, one of the most costly diseases in society. The aetiology of schizophrenia is unknown, and there is no cure. The main aims of therapy with antipsychotic medication include the effective relief of symptoms without the introduction of adverse effects or serious adverse events, improved quality of life, cost effectiveness and a positive long term outcome. The older classical antipsychotic drugs do not always meet these requirements because of their well-known limitations, such as a lack of response in a subgroup of individuals with schizophrenia and intolerable adverse effects. There has long been a need for new antipsychotics that can ameliorate more symptoms and have no or few adverse effects. Some of the recently introduced antipsychotics have been shown to be more effective in certain clinical situations and to have a more favourable adverse effect profile than the classical antipsychotics. A major factor contributing to the lower effectiveness of drug treatment is noncompliance, which may be very high in schizophrenia. There are several factors influencing compliance, including drug type and formulation, patient, disease status, physician, health care system, community care and family. There have been very few studies of compliance improvement strategies in schizophrenia or, indeed, in medicine in general. Current methods are relatively complex and there are differing opinions on their effectiveness. There are several ways to increase compliance in schizophrenia--the evidence is strongest for psychoeducative methods, changing to a new drug or using a depot formulation. However, considerably more research is needed in the field of compliance strategies.

[Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

PubMed

Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

2009-01-01

With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

PubMed Central

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-01-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248

Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders.

PubMed

Espejo, Emmanuel P; Hammen, Constance L; Connolly, Nicole P; Brennan, Patricia A; Najman, Jake M; Bor, William

2007-04-01

The goal of the present study was to determine whether exposure to adversity in childhood contributes to a differential threshold at which stressful life events provoke depressive reactions in adolescence. In addition, to address empirical and conceptual questions about stress effects, the moderating effect of anxiety disorder history was also explored. This examination was conducted in a sample of 816 children of depressed and nondepressed mothers, who were followed from birth to age 15. Information on adversities experienced in childhood was collected both from mothers during the first five years of their youth's life and from the youths themselves at age 15, and included information on the mother's relationship with her partner, maternal psychopathology, as well as youth-reported abuse. Results indicated that youths with both greater exposure to adversity in childhood and a history of an anxiety disorder displayed increased depressive severity following low levels of episodic stress compared to youths with only one or neither of these risk factors. The results are speculated to reflect the possibility that early anxiety disorders associated with exposure to adversity in childhood may be a marker of dysregulated stress responses, and may help to account for the comorbidity of depression and anxiety in some individuals.

Comparing the Effectiveness and Safety of the Addition of and Switching to Aripiprazole for Resolving Antipsychotic-Induced Hyperprolactinemia: A Multicenter, Open-Label, Prospective Study.

PubMed

Yoon, Hui Woo; Lee, Jung Suk; Park, Sang Jin; Lee, Seon-Koo; Choi, Won-Jung; Kim, Tae Yong; Hong, Chang Hyung; Seok, Jeong-Ho; Park, Il-Ho; Son, Sang Joon; Roh, Daeyoung; Kim, Bo-Ra; Lee, Byung Ook

Hyperprolactinemia is an important but often overlooked adverse effect of antipsychotics. Several studies have shown that switching to or adding aripiprazole normalizes antipsychotic-induced hyperprolactinemia. However, no study has directly compared the effectiveness and safety of the 2 strategies. A total of 52 patients with antipsychotic-induced hyperprolactinemia were recruited. Aripiprazole was administered to patients with mild hyperprolactinemia (serum prolactin level < 50 ng/mL). Patients with severe hyperprolactinemia (serum prolactin level > 50 ng/mL) were randomized to an aripiprazole-addition group (adding aripiprazole to previous antipsychotics) or a switching group (switching previous antipsychotics to aripiprazole). Serum prolactin level, menstrual disturbances, sexual dysfunction, psychopathologies, and quality of life were measured at weeks 0, 1, 2, 4, 6, and 8. Both the addition and switching groups showed significantly reduced serum prolactin level and menstrual disturbances and improved sexual dysfunction. In patients with severe hyperprolactinemia, the numbers of patients with hyperprolactinemia and menstrual disturbance in the switching group were significantly lower than those in the addition group at week 8. Both the addition and switching strategies were effective in resolving antipsychotic-induced hyperprolactinemia and hyperprolactinemia-related adverse events, including menstrual disturbances and sexual dysfunction. In addition, these findings suggest that switching to aripiprazole may be more effective than addition of aripiprazole for normalizing hyperprolactinemia and improving hyperprolactinemia-related adverse events in patients with schizophrenia.

Effects of childhood adversity on bullying and cruelty to animals in the United States: findings from a national sample.

PubMed

Vaughn, Michael G; Fu, Qiang; Beaver, Kevin M; Delisi, Matt; Perron, Brian E; Howard, Matthew O

2011-11-01

This study examined effects of type of and cumulative burden of childhood adversities on bullying and cruelty to animals in the United States. Data were derived from Waves I and II of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of U.S. adults. Structured psychiatric interviews were completed by trained lay interviewers between 2001-2002 and 2003-2004. Although the effects of childhood adversity diminished with the inclusion of confounding variables, several adversities remained significant. For bullying, these included being made to do chores that were too difficult or dangerous, threatening to hit or throw something, pushing, shoving, slapping, or hitting, and hitting that left bruises, marks, or injuries. With respect to cruelty to animals, swearing and saying hurtful things, having a parent or other adult living within the home that went to jail or prison, and adult/other person fondling/touching in a sexual way were significant. The final models indicated that the cumulative burden of childhood adversities had strong effects on the increased likelihood of bullying behavior but not cruelty to animals.

[Mechanism of leukocytapheresis effect in the treatment of ulcerative colitis].

PubMed

Sawada, K; Ohnishi, K; Fukunaga, K; Chikano, S; Egashira, A; Satomi, M; Shimoyama, T

1999-12-01

To solve adverse effects of high dose steroid administration for patients with moderately severe and severe ulcerative colitis (UC), additional use of leukocytapheresis (LCAP) was tried to settle colonic inflammation. We evaluated immunological changes in the treatment of LCAP using leukocyte removal filter for UC patients. We then assessed the clinical effectiveness of LCAP compared with that of high dose of steroid therapy. LCAP removed monocytes, granulocytes, and lymphocytes presenting CD 11 b+, CD 11 c+, and HLADR+, selectively from the patients. Proinflammatory cytokine productions measured such as TNF alpha, IL-1 beta, and IL 8 reduced and IL 10 increased immediately after LCAP compared with before perfusion. Improved rate was about 70% for LCAP group and about 40% for high dose steroid group (Refer J Gastroenterol). Selective removal of granulocyte, monocytes, and activated lymphocytes inhibits proinflammatory cytokine production and increases immune modulating cytokine productions (Refer Therapeutic Apheresis). Then quick inhibition of several inflammatory deteriorated factors simultaneously controls the activity and clinical symptoms of UC with less severe adverse effects. It can be considered one option for treatment of UC.

Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report.

PubMed

Stuhec, Matej

2014-01-01

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

Coexisting lumbar spondylosis in patients undergoing TKA: how common and how serious?

PubMed

Chang, Chong Bum; Park, Kun Woo; Kang, Yeon Gwi; Kim, Tae Kyun

2014-02-01

Information on the coexistence of lumbar spondylosis and its influence on overall levels of pain and function in patients with advanced knee osteoarthritis (OA) undergoing total knee arthroplasty (TKA) would be valuable for patient consultation and management. The purposes of this study were to document the prevalence and severity of coexisting lumbar spondylosis in patients with advanced knee OA undergoing TKA and to determine whether the coexisting lumbar spondylosis at the time of TKA adversely affects clinical scores in affected patients before and 2 years after TKA. Radiographic lumbar spine degeneration and lumbar spine symptoms including lower back pain, radiating pain at rest, and radiating pain with activity were assessed in 225 patients undergoing TKA. In addition, the WOMAC score and the SF-36 scores were evaluated before and 2 years after TKA. Potential associations of radiographic lumbar spine degeneration and lumbar spine symptom severities with pre- and postoperative WOMAC subscales and SF-36 scores were examined. All 225 patients had radiographic degeneration of the lumbar spine, and the large majority (89% [200 of 225]) had either moderate or severe spondylosis (72% and 17%, respectively). A total of 114 patients (51%) had at least one moderate or severe lumbar spine symptom. No association was found between radiographic severity of lumbar spine degeneration and pre- and postoperative clinical scores. In terms of lumbar spine symptoms, more severe symptoms were likely to adversely affect the preoperative WOMAC and SF-36 physical component summary (PCS) scores, but most of these adverse effects improved by 2 years after TKA with the exception of the association between severe radiating pain during activity and a poorer postoperative SF-36 PCS score (regression coefficient = -5.41, p = 0.015). Radiographic lumbar spine degeneration and lumbar spine symptoms are common among patients with advanced knee OA undergoing TKA. Severe lumbar spine symptoms (visual analog scale score of ≥ 7) were likely to adversely affect the preoperative clinical scores of patients undergoing TKA; however, most of the adverse effects were not found 2 years after TKA. Nevertheless, because preexisting severe radiating pain during activity may be a source of a poorer outcome after TKA, careful patient consultation regarding this potential poorer prognosis after TKA needs to be provided to the patient with this symptom.

Adverse Effects of GLP-1 Receptor Agonists

PubMed Central

Filippatos, Theodosios D.; Panagiotopoulou, Thalia V.; Elisaf, Moses S.

2014-01-01

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists. PMID:26177483

Physiochemical properties and application of hyaluronic acid: a systematic review.

PubMed

Salwowska, Natalia M; Bebenek, Katarzyna A; Żądło, Dominika A; Wcisło-Dziadecka, Dominika L

2016-12-01

Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine. We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners. We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria. Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved. Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields. © 2016 Wiley Periodicals, Inc.

Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis.

PubMed

Krogh, Jesper; Hjorthøj, Carsten; Speyer, Helene; Gluud, Christian; Nordentoft, Merete

2017-09-18

To assess the benefits and harms of exercise in patients with depression. Systematic review DATA SOURCES: Bibliographical databases were searched until 20 June 2017. Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention. Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was -0.66 standardised mean difference (SMD) (95% CI -0.86 to -0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into -0.11 SMD (-0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes. Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes. The protocol was published in the journal Systematic Reviews : 2015; 4:40. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop.

PubMed

Lenz, B; Braendli-Baiocco, A; Engelhardt, J; Fant, P; Fischer, H; Francke, S; Fukuda, R; Gröters, S; Harada, T; Harleman, H; Kaufmann, W; Kustermann, S; Nolte, T; Palazzi, X; Pohlmeyer-Esch, G; Popp, A; Romeike, A; Schulte, A; Lima, B Silva; Tomlinson, L; Willard, J; Wood, C E; Yoshida, M

2018-02-01

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.

Energy Drink Consumption: Beneficial and Adverse Health Effects.

PubMed

Alsunni, Ahmed Abdulrahman

2015-10-01

Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

PubMed Central

Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

2010-01-01

Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events. PMID:20725567

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

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

PubMed

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

2017-12-01

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

Evaluation of perampanel in patients with intellectual disability and epilepsy.

PubMed

Snoeijen-Schouwenaars, Francesca M; van Ool, Jans S; Tan, In Y; Schelhaas, Helenius J; Majoie, Marian H J M

2017-01-01

Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population. Retrospective evaluation of medical records at 3, 6 and 12months of follow-up after the initial start of PMP. 62 patients were included. 21 patients (33.9%) were female. All patients had complete data of 6months follow-up and we were able to review 42 patients with a 1-year follow-up. Level of ID varied from borderline to profound, and mild ID was most common (43.5%). The mean maximum daily dosage of PMP was 5.6mg (range 1-12mg). Retention rates for PMP were 87.1% and 67.7% after three and six months. A trend indicated a longer mean retention time in patients with a more severe ID (borderline-mild-moderate ID: 205days, severe-profound ID: 275days). Seizure reduction was achieved in 53.2%. 36 patients (58.1%) experienced adverse effects, 80.6% of those within 3months. 45.2% of the patients experienced somatic adverse effects. Most common were fatigue & sleep problems, motor problems & unsteadiness, and gastrointestinal problems. Behavioral adverse effects were present in 40.3%. Most common were aggression, agitated behavior, disruptive behavior, and mood symptoms. Reasons for discontinuation of PMP were lack of efficacy in 14.8%, intolerable adverse effects in 44.4%, and a combination of both in 40.7%. Altogether, 24.2% (15/62) of the patients achieved seizure reduction without experiencing adverse effects, though none reached seizure freedom. The use of PMP might lead to an effective seizure reduction without adverse effects in a minority of patients with both epilepsy and ID. Pre-existing behavioral problems or polypharmacy do not predict the occurrence of additional behavioral adverse effects, implying that these patients need not be excluded from the introduction of PMP when clinically indicated. Patients should, ideally, be monitored at a multidisciplinary clinic. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

PubMed Central

Montejo, Angel L.; Montejo, Laura; Baldwin, David S.

2018-01-01

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment‐related sexual adverse events tend to persist over time, and are unfortunately under‐recognized by clinicians and scarcely investigated in clinical trials. Treatment‐emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction. PMID:29352532

Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream in chinese patients with melasma: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study.

PubMed

Gong, Zijian; Lai, Wei; Zhao, Guang; Wang, Xuemin; Zheng, Min; Li, Li; Yang, Qingqi; Dang, Yuping; Liu, Lunfei; Zou, Ying

2015-06-01

This study aimed to determine the efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin (FAHT) cream for the treatment of moderate and severe facial melasma. The primary objective was assessment of clinical efficacy, instrumental measured efficacy, and integral therapeutic efficacy at the end of weeks 4 and 8. A total of 233 subjects were randomly allocated (1:1 ratio) to receive topically administered FAHT cream (n = 117) or placebo (n = 116) once nightly for 8 weeks. Observed side effects were documented throughout. In the per protocol set (PPS; those subjects who met all requirements of the protocol), the integral therapeutic efficacy rate of FAHT cream on moderate and severe melasma was 68.57% (vs. placebo, 0.94%), the clinical effective rate of FAHT cream was 74.29 % (vs. placebo, 0.94%), and the instrumental measure efficacy of FAHT cream was 71.43% (vs. placebo, 6.60%). The difference in efficacy between the two groups was statistically significant (p < 0.001). In the full analysis set (FAS; the PPS and those subjects who were lost to follow-up but received at least one study treatment), the integral therapeutic efficacy rate of FAHT cream was 64.60% (vs. placebo, 0.88%), the clinical effective rate of FAHT cream was 69.91% (vs. placebo, 0.88%), and the instrumental measure efficacy of FAHT cream was 69.03 % (vs. placebo, 7.08%). The difference in efficacy between the two groups was statistically significant (p < 0.001). Of 113 subjects in the FAHT group, 34 (30.1%) reported adverse effects. Most of the pathological adverse effects were mild and resolved with either continuous treatment or discontinuation. Of 113 subjects in the placebo group, three (2.6%) reported mild adverse effects. No severe adverse effects or other abnormal clinical results were associated with the study treatment. FAHT cream is efficacious, well tolerated, and has a high margin of safety for the treatment of moderate and severe melasma in the Chinese population.

Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement.

PubMed

Trost, Landon W; Serefoglu, Ege; Gokce, Ahmet; Linder, Brian J; Sartor, Alton O; Hellstrom, Wayne J G

2013-02-01

Androgen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality. The current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT. A PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution. Reported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported. ADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy. Patients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy. © 2013 International Society for Sexual Medicine.

Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

PubMed Central

Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

2013-01-01

Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera).

PubMed

Christen, Verena; Mittner, Fabian; Fent, Karl

2016-04-05

Neonicotinoids are implicated in the decline of bee populations. As agonists of nicotinic acetylcholine receptors, they disturb acetylcholine receptor signaling leading to neurotoxicity. Several behavioral studies showed the link between neonicotinoid exposure and adverse effects on foraging activity and reproduction. However, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic levels of three neonicotinoids and nicotine, and compared laboratory studies to field exposures with acetamiprid. We assessed transcriptional alterations of eight selected genes in caged honey bees exposed to different concentrations of the neonicotinoids acetamiprid, clothianidin, imidacloporid, and thiamethoxam, as well as nicotine. We determined transcripts of several targets, including nicotinic acetylcholine receptor α 1 and α 2 subunit, the multifunctional gene vitellogenin, immune system genes apidaecin and defensin-1, stress-related gene catalase and two genes linked to memory formation, pka and creb. Vitellogenin showed a strong increase upon neonicotinoid exposures in the laboratory and field, while creb and pka transcripts were down-regulated. The induction of vitellogenin suggests adverse effects on foraging activity, whereas creb and pka down-regulation may be implicated in decreased long-term memory formation. Transcriptional alterations occurred at environmental concentrations and provide an explanation for the molecular basis of observed adverse effects of neonicotinoids to bees.

Concurrent adversities among adolescents with conduct problems: the NAAHS study.

PubMed

Reigstad, Bjørn; Kvernmo, Siv

2016-10-01

Several studies have confirmed that maltreatment and abuse in childhood are related to conduct problems. Less is known about such relationships with concurrent adversities in adolescence and, also, when compared with other severe adversities and possible multiple additive effects. The study encompassed a community population of 4881 adolescents 15-16 years of age 50.1 % boys and 49.9 % girls. Youth with and without conduct problem scores within the deviant range on the Strength and Difficulties Questionnaire (SDQ) was compared on 12 concurrent adversities. Based on self-reports, 4.4 % of the adolescents had conduct problem scores within the deviant range and more girls (5.1 %) than boys (3.7 %). In the deviant conduct problem group, 65.1 % had experienced two or more concurrent adversities compared with 26.3 % of youths in the non-deviant group (OR 5.23, 95 % CI 3.91-7.01). Likewise, the deviant conduct problem group was from 1.71 to 8.43 times more at the risk of experiencing the different adversities. Parental mental health problems and experiences of violence were multivariately strongest associated with conduct problem scores within the deviant range on the SDQ. A strong multiple additive relationship with adversities was found. Two-thirds of youth with SDQ conduct problem scores within the deviant range reported two or more concurrent adversities. Clinicians should seek information about kinds and amount of possible traumatic adversities in youth with conduct problems and offer evidence based treatment.

Repeated pulse intramuscular injection of pralidoxime chloride in severe acute organophosphorus pesticide poisoning.

PubMed

Tang, Xue; Wang, Ruilan; Xie, Hui; Hu, Jiachang; Zhao, Wenbiao

2013-06-01

This study aimed to clarify the efficacy of 2 therapies for patients with severe acute organophosphorus pesticide poisoning, including atropine adverse effects, the length of intensive care unit (ICU) stay, complications, and mortality. A retrospective cohort study of 152 cases collected from May 2008 to November 2012 at 2 urban university hospitals was conducted. Patients admitted to the hospital for organophosphate poisoning were divided into 2 groups with different therapeutic regimens: group A was administered a repeated pulse intramuscular injection of pralidoxime chloride, and group B received the same initial dosage of atropine and pralidoxime chloride, but pralidoxime chloride intravenous therapy was administered for only 3 days, regardless of the length of atropine therapy. Subsequently, atropine adverse effects, length of ICU stay, complications, and mortality were statistically analyzed and compared between the 2 groups. The total dose of atropine was 57.40 ± 15.14 mg in group A and 308.26 ± 139.16 mg in group B; group A received less atropine than did group B (P = .001). The length of ICU stay in group A was reduced (P = .025), and group A had fewer atropine adverse effects (P = .002). However, there was no significant difference in the mortality or complication rate between the 2 groups (P > .05). In patients with severe poisoning, group A used less atropine, had fewer atropine adverse effects, and had a shorter ICU stay. We suggest that therapy should be started as early as possible using a sufficient amount of pralidoxime chloride started intramuscularly in combination with atropine and that the drugs should not be prematurely discontinued. Copyright © 2013 Elsevier Inc. All rights reserved.

Energy drink exposures reported to Texas poison centers: Analysis of adverse incidents in relation to total sales, 2010-2014.

PubMed

Borron, Stephen W; Watts, Susan H; Herrera, Jessica; Larson, Joshua; Baeza, Salvador; Kingston, Richard L

2018-05-21

The ill-defined term "energy drink" includes a disparate group of products (beverages, shots, concentrates, and workout powders) having large differences in caffeine content and concentration and intended use. Hence, inaccurate conclusions may be drawn when describing adverse events associated with "energy drinks". The FDA is considering new regulation of these products but product specificity is needed to evaluate safety. To help address this, we queried Texas Poison Center Network data for single substance exposures to "energy drinks" from 2010 to 2014, then analyzed adverse events by product type. We specifically compared energy beverage exposures with sales data for the same time period to evaluate the safety profile of this category of energy drinks. Among 855 documented "energy drink" exposures, poison center-determined outcome severity revealed 291 with no/minimal effects, 417 judged nontoxic or minor/not followed, 64 moderate and 4 major effects, and no deaths. Serious complications included 2 seizures and 1 episode of ventricular tachycardia. Outcome severity by category for beverages: 11 moderate/1 major effects (none in children <17 years); shots: 19 moderate/2 major; non-liquids: 16 moderate/1 major; concentrates: 7 moderate; unknown: 10 moderate. Call incidence to poison centers for beverage type exposures was 0.58 (for moderate effects) and 0.053 (for major) per hundred million units sold. Small volume and concentrated products were associated with a greater number of adverse effects than beverage versions of "energy drinks". Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-08-01

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

Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

PubMed

Wang, Yan; Fu, Wei; Liu, Jing

2016-01-01

Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: a descriptive case report.

PubMed

Puliyel, Mammen M; Pillai, Rajappan; Korula, Sophy

2009-02-01

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.

Switching of biologics in psoriasis: Reasons and results.

PubMed

Honda, Hiromi; Umezawa, Yoshinori; Kikuchi, Sota; Yanaba, Koichi; Fukuchi, Osamu; Ito, Toshihiro; Nobeyama, Yoshimasa; Asahina, Akihiko; Nakagawa, Hidemi

2017-09-01

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. © 2017 Japanese Dermatological Association.

Effects of Childhood Adversity on Bullying and Cruelty to Animals in the United States: Findings From a National Sample

PubMed Central

Vaughn, Michael G.; Fu, Qiang; Beaver, Kevin M.; DeLisi, Matt; Perron, Brian E.; Howard, Matthew O.

2012-01-01

This study examined effects of type of and cumulative burden of childhood adversities on bullying and cruelty to animals in the United States. Data were derived from Waves I and II of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of U.S. adults. Structured psychiatric interviews were completed by trained lay interviewers between 2001–2002 and 2003–2004. Although the effects of childhood adversity diminished with the inclusion of confounding variables, several adversities remained significant. For bullying, these included being made to do chores that were too difficult or dangerous, threatening to hit or throw something, pushing, shoving, slapping, or hitting, and hitting that left bruises, marks, or injuries. With respect to cruelty to animals, swearing and saying hurtful things, having a parent or other adult living within the home that went to jail or prison, and adult/other person fondling/touching in a sexual way were significant. The final models indicated that the cumulative burden of childhood adversities had strong effects on the increased likelihood of bullying behavior but not cruelty to animals. PMID:21602208

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

PubMed

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

2017-01-01

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

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

PubMed Central

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

Application of ToxCast to evaluate potential biological effects ...

EPA Pesticide Factsheets

With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemicals with more than 800 assays. The original intent of this data was to evaluate potential for human health effects, but it is now being extended to environmental health evaluations. The R package ToxEval was developed as a screening tool to use ToxCast results for evaluation of potential adverse biological effects from trace organic chemicals in water samples. Using ToxEval, trace organic chemical data from water samples and passive samplers collected at 57 Great Lakes tributaries from 2010-2013 were examined to determine the tributaries with the greatest potential for adverse biological effects with prioritization of the most influential contaminants. Results are being used as part of the Great Lakes Restoration Initiative to focus current and future investigations that will help understand likely adverse outcome pathways in biological organisms, and to formulate possible remediation strategies. not applicable

Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine.

PubMed

Koppen, A; van Riel, A; de Vries, I; Meulenbelt, J

2014-06-01

Treatment of paracetamol intoxication consists of administration of N-acetylcysteine, preferably shortly after paracetamol ingestion. In most countries, the decision to treat patients with N-acetylcysteine depends on the paracetamol plasma concentration. In the literature, different arguments are given regarding when to treat paracetamol overdose. Some authors do not recommend treatment with N-acetylcysteine at low paracetamol plasma concentrations since unnecessary adverse effects may be induced. But no treatment with N-acetylcysteine at higher paracetamol plasma concentrations may lead to unnecessary severe morbidity and mortality. In this review, we provide an overview on the severity and prevalence of adverse side effects after N-acetylcysteine administration and the consequences these side effects may have for the treatment of paracetamol intoxication. The final conclusion is to continue using the guidelines of the Dutch National Poisons Information Centre for N-acetylcysteine administration in paracetamol intoxication.

Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak

PubMed Central

Lancee, William J.; Balderson, Kenneth E.; Bennett, Jocelyn P.; Borgundvaag, Bjug; Evans, Susan; Fernandes, Christopher M.B.; Goldbloom, David S.; Gupta, Mona; Hunter, Jonathan J.; Hall, Linda McGillis; Nagle, Lynn M.; Pain, Clare; Peczeniuk, Sonia S.; Raymond, Glenna; Read, Nancy; Rourke, Sean B.; Steinberg, Rosalie J.; Stewart, Thomas E.; Coke, Susan VanDeVelde; Veldhorst, Georgina G.; Wasylenki, Donald A.

2006-01-01

Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks. PMID:17326946

Cumulative burden of lifetime adversities: Trauma and mental health in low-SES African Americans and Latino/as.

PubMed

Myers, Hector F; Wyatt, Gail E; Ullman, Jodie B; Loeb, Tamra B; Chin, Dorothy; Prause, Nicole; Zhang, Muyu; Williams, John K; Slavich, George M; Liu, Honghu

2015-05-01

This study examined the utility of a lifetime cumulative adversities and trauma model in predicting the severity of mental health symptoms of depression, anxiety, and posttraumatic stress disorder. We also tested whether ethnicity and gender moderate the effects of this stress exposure construct on mental health using multigroup structural equation modeling. A sample of 500 low-socioeconomic status African American and Latino men and women with histories of adversities and trauma were recruited and assessed with a standard battery of self-report measures of stress and mental health. Multiple-group structural equation models indicated good overall model fit. As hypothesized, experiences of discrimination, childhood family adversities, childhood sexual abuse, other childhood trauma, and chronic stresses all loaded on the latent cumulative burden of adversities and trauma construct (CBAT). The CBAT stress exposure index in turn predicted the mental health status latent variable. Although there were several significant univariate ethnic and gender differences, and ethnic and gender differences were observed on several paths, there were no significant ethnic differences in the final model fit of the data. These findings highlight the deleterious consequences of cumulative stress and trauma for mental health and underscore a need to assess these constructs in selecting appropriate clinical interventions for reducing mental health disparities and improving human health. (c) 2015 APA, all rights reserved).

Energy, Weatherization and Indoor Air Quality

EPA Pesticide Factsheets

Climate change presents many challenges, including the production of severe weather events. These events and efforts to minimize their effects through weatherization can adversely affect indoor environments.

Hydration and blood volume effects on human thermoregulation in the heat: Space applications

NASA Technical Reports Server (NTRS)

Sawka, Michael N.; Gonzalez, Richard R.; Pandolf, Kent B.

1994-01-01

Astronauts exposed to prolonged weightlessness will experience deconditioning, dehydration, and hypovolemia which all adversely affect thermoregulation. These thermoregulatory problems can be minimized by several countermeasures that manipulate body water and vascular volumes. USARIEM scientists have extensively studied dehydration effects and several possible countermeasures including hyperhydration, plasma and erythrocyte volume expansion. This paper reviews USARIEM research into these areas.

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

Musette, Philippe; Kaufman, Jean-Marc; Rizzoli, René; Cacoub, Patrice; Brandi, Maria Louisa; Reginster, Jean-Yves

2011-01-01

Cutaneous adverse reactions are reported for many therapeutic agents and, in general, are observed in between 0% and 8% of treated patients depending on the drug. Antiosteoporotic agents are considered to be safe in terms of cutaneous effects, however there have been a number of case reports of cutaneous adverse reactions which warrant consideration. This was the subject of a working group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, which focused on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. This position paper was drafted following these discussions and includes a flowchart for their recognition. Cutaneous adverse reactions observed with antiosteoporotic agents were reviewed and included information from case reports, regulatory documents and pharmacovigilance. These reactions ranged from benign effects including exanthematous or maculopapular eruption (drug rash), photosensitivity and urticaria, to the severe and potentially life-threatening reactions of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome and toxic epidermal necrolysis. A review of the available evidence demonstrates that cutaneous adverse reactions occur with all commonly used antiosteoporotic treatments. Notably, there are reports of Stevens Johnson syndrome and toxic epidermal necrolysis for bisphosphonates, and of DRESS and toxic epidermal necrolysis for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases). In general, with proper management and early recognition, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration and systemic corticosteroids if necessary, the prognosis is positive. PMID:22870464

Use of electroconvulsive therapy (ECT) in postpartum psychosis--a naturalistic prospective study.

PubMed

Babu, Girish N; Thippeswamy, Harish; Chandra, Prabha S

2013-06-01

Postpartum psychosis (PPP) is a severe psychiatric condition requiring rapid restoration of health in view of significant risks to both mother and the infant. Electroconvulsive therapy (ECT) is often used for treatment of severe PPP. The aims of the study were to describe the indications for ECT among women admitted with PPP to a psychiatric hospital in India. It also aimed at assessing whether women with PPP who received ECT differed in their clinical history, diagnosis, severity of illness, psychopathology, drug dosage, and duration of hospital stay, compared to women who did not receive ECT. Infants of mothers who were breast-feeding their infants while receiving ECT were assessed for adverse effects. This was a naturalistic prospective study of 78 women admitted with PPP, 34 (43.6 %) of whom received ECT. Presence of catatonia, augmentation of medications, and suicidality were common indications for ECT. Catatonic symptoms were significantly higher among women who received ECT. There was no significant difference in duration of hospitalization or severity of psychopathology between women who did and did not receive ECT. Transient side effects to ECT were observed in few women, with no adverse effects noted in infants who were breast-fed. The current study supports the use of ECT as an effective and safe treatment for women with severe PPP.

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

PubMed Central

Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

2016-01-01

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

PubMed

Puterman, Eli; Gemmill, Alison; Karasek, Deborah; Weir, David; Adler, Nancy E; Prather, Aric A; Epel, Elissa S

2016-10-18

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Classifying Adverse Events in the Dental Office.

PubMed

Kalenderian, Elsbeth; Obadan-Udoh, Enihomo; Maramaldi, Peter; Etolue, Jini; Yansane, Alfa; Stewart, Denice; White, Joel; Vaderhobli, Ram; Kent, Karla; Hebballi, Nutan B; Delattre, Veronique; Kahn, Maria; Tokede, Oluwabunmi; Ramoni, Rachel B; Walji, Muhammad F

2017-06-30

Dentists strive to provide safe and effective oral healthcare. However, some patients may encounter an adverse event (AE) defined as "unnecessary harm due to dental treatment." In this research, we propose and evaluate two systems for categorizing the type and severity of AEs encountered at the dental office. Several existing medical AE type and severity classification systems were reviewed and adapted for dentistry. Using data collected in previous work, two initial dental AE type and severity classification systems were developed. Eight independent reviewers performed focused chart reviews, and AEs identified were used to evaluate and modify these newly developed classifications. A total of 958 charts were independently reviewed. Among the reviewed charts, 118 prospective AEs were found and 101 (85.6%) were verified as AEs through a consensus process. At the end of the study, a final AE type classification comprising 12 categories, and an AE severity classification comprising 7 categories emerged. Pain and infection were the most common AE types representing 73% of the cases reviewed (56% and 17%, respectively) and 88% were found to cause temporary, moderate to severe harm to the patient. Adverse events found during the chart review process were successfully classified using the novel dental AE type and severity classifications. Understanding the type of AEs and their severity are important steps if we are to learn from and prevent patient harm in the dental office.

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

PubMed

Helfenstein, M; Zweifel, S; Barthelmes, D; Meier, F; Fehr, J; Böni, C

2017-04-01

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management. Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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

2009-03-01

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

Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions†

PubMed Central

Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

2016-01-01

This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules—namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

Time does not heal all wounds: older adults who experienced childhood adversities have higher odds of mood, anxiety, and personality disorders.

PubMed

Raposo, Sarah M; Mackenzie, Corey S; Henriksen, Christine A; Afifi, Tracie O

2014-11-01

We aimed to examine the prevalence of several types of childhood adversity across adult cohorts, whether age moderates the effect of childhood adversity on mental health, the relationship between childhood adversity and psychopathology among older adults, the dose-response relationship between number of types of childhood adversities and mental disorders in later life, and whether lifetime mental health treatment reduces the odds of psychopathology among older survivors of childhood adversity. In a population-based, cross-sectional study on a nationally representative U.S. sample, we studied 34,653 community-dwelling Americans 20 years and older, including 7,080 adults 65 years and older from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Trained lay interviewers assessed past-year mood and anxiety disorders and lifetime personality disorders. Participants self-reported childhood adversity based on questions from the Adverse Childhood Experiences Study. Childhood adversity was prevalent across five age cohorts. In our adjusted models, age did not moderate the effect of childhood adversity on mental disorders. Older adults who experienced childhood adversity had higher odds of having mood (odds ratio: 1.73; 95% confidence interval: 1.32-2.28), anxiety (odds ratio: 1.48; 95% confidence interval: 1.20-1.83), and personality disorders (odds ratio: 2.11; 95% confidence interval: 1.75-2.54) after adjusting for covariates. An increasing number of types of childhood adversities was associated with higher odds of personality disorders and somewhat higher odds of anxiety disorders. Treatment-seeking was associated with a reduced likelihood of anxiety and, especially, mood disorders in older adult childhood adversity survivors. These results emphasize the importance of preventing childhood adversity and intervening once it occurs to avoid the negative mental health effects that can last into old age. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1

PubMed Central

Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

2016-01-01

Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6–43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10−5). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes. PMID:27271856

Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.

PubMed

Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

2016-06-07

Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

PubMed

Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

Severity of statin-induced adverse effects on muscle and associated conditions: data from the DAMA study.

PubMed

Pedro-Botet, Juan; Millán Núñez-Cortés, Jesús; Chillarón, Juan J; Flores-Le Roux, Juana A; Rius, Joan

2016-12-01

Statins are generally well tolerated, but muscular adverse effects appear to be the most common obstacle limiting their use. Our objective was to describe the severity of muscle injury (myalgia, myositis and rhabdomyolysis) and associated conditions related to statin therapy that may be clinically significant. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. Clinical, biochemical and drug therapy characteristics were obtained at the initial evaluation. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients, myositis in 19.3% and rhabdomyolysis in 2.5%. The prevalence of different comorbidities such as diabetes, hypertension, atrial fibrillation, and coronary heart disease increased as the severity of myopathy rose. High-intensity statin therapy was used in 33.4% of patients. Concomitant drugs metabolized by the CYP450 3A4 pathway were taken by 9.3% of patients, and statins with this metabolic route by 75%. Independent variables associated with myositis or rhabdomyolysis compared with myalgia alone in the multivariate model were excessive alcohol consumption and pravastatin therapy. Myalgia was the most common muscle adverse effect associated with statin therapy. Excessive alcohol consumption and pravastatin were independently associated with myositis or rhabdomyolysis.

Mechanism-Driven Phase I Translational Study of Trifluoperazine in Adults with Sickle Cell Disease

PubMed Central

Molokie, Robert E.; Wilkie, Diana J.; Wittert, Harriett; Suarez, Marie L.; Yao, Yingwei; Zhao, Zhongsheng; He, Ying; Wang, Zaijie J.

2014-01-01

Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca2+/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10 mg), we obtained 7-hourly and 24-hour repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8 ± 8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10 mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5 hrs after the 10 mg dose. The analgesic effect lasted for at least 24 hrs in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10 mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1 mg in repeated doses to determine long-term adverse and analgesic effects. PMID:24211787

Obesity and type 2 diabetes risk in midadult life: the role of childhood adversity.

PubMed

Thomas, Claudia; Hyppönen, Elina; Power, Chris

2008-05-01

Child abuse has been associated with poorer physical health in adulthood, but less is known about childhood adversity more broadly, including neglect and family problems, or the pathways from adversity to adult disease. We have examined how different stressful emotional or neglectful childhood adversities are related to adiposity and glucose control in midadulthood, taking into account childhood factors, and whether the relationships are mediated by adult health behaviors and socioeconomic position. This was a prospective longitudinal study of 9310 members of the 1958 British birth cohort who participated in a biomedical interview at 45 years of age. Primary outcomes consisted of continuous measures of BMI, waist circumference, and glycosylated hemoglobin at 45 years and categorical indicators: total obesity (BMI > or = 30), central obesity (waist circumference: > or = 102 cm for men and > or = 88 cm for women), and glycosylated hemoglobin level of > or = 6. The risk of obesity increased by 20% to 50% for several adversities (physical abuse, verbal abuse, witnessed abuse, humiliation, neglect, strict upbringing, physical punishment, conflict or tension, low parental aspirations or interest in education, hardly takes outings with parents, and father hardly reads to child). Adversities with the strongest associations with adiposity (eg, physical abuse) tended to be associated with glycosylated hemoglobin levels of > or = 6, but in most cases associations were explained by adjustment for adulthood mediators such as adiposity. Effects of other adversities reflecting less severe emotional neglect and family environment were largely explained by childhood socioeconomic factors. Some childhood adversities increase the risk of obesity in adulthood and thereby increase the risk for type 2 diabetes. Research is needed to understand the interrelatedness of adversities, the social context of their occurrence, and trajectories from adversity to adult disease.

12 CFR 360.10 - Resolution plans required for insured depository institutions with $50 billion or more in total...

Code of Federal Regulations, 2013 CFR

2013-01-01

... that failure of the CIDI may occur under the baseline, adverse and severely adverse economic conditions...) Assessing the feasibility of the CIDI's plans, under baseline, adverse and severely adverse economic... conducted by the CIDI since the date of the most recently filed resolution plan to assess the viability of...

12 CFR 360.10 - Resolution plans required for insured depository institutions with $50 billion or more in total...

Code of Federal Regulations, 2014 CFR

2014-01-01

... that failure of the CIDI may occur under the baseline, adverse and severely adverse economic conditions...) Assessing the feasibility of the CIDI's plans, under baseline, adverse and severely adverse economic... conducted by the CIDI since the date of the most recently filed resolution plan to assess the viability of...

Environmental adversities and psychotic symptoms: The impact of timing of trauma, abuse, and neglect.

PubMed

Schalinski, Inga; Breinlinger, Susanne; Hirt, Vanessa; Teicher, Martin H; Odenwald, Michael; Rockstroh, Brigitte

2017-11-13

Trauma and adverse childhood experiences (ACE) occur more often in mental illness, including psychosis, than in the general population. Individuals with psychosis (cases) report a higher number and severity (dose) of adversities than healthy controls. While a dose-dependent increase of adversities has been related to more severe psychopathology, the role of type and timing is still insufficiently understood on the exacerbation of positive and negative psychotic symptoms. Moreover, dissociative symptoms were examined as potential mediator between adversities and severity of psychotic symptoms. Exposure to adversities were assessed by interviews in n=180 cases and n=70 controls. In cases, symptom severities were obtained for psychotic symptoms and dissociation. Conditioned random forest regression determined the importance of type and timing of ACE for positive and negative symptom severity, and mediator analyses evaluated the role of dissociative symptoms in the relationship between adversities and psychotic symptoms. Cases experienced substantially more abuse and neglect than controls. Adversities were related in a dose-dependent manner to psychotic disorder. An array of adversities was associated with more severe positive symptoms, while the conditioned random forest regression depicted neglect at age 10 as the most important predictor. Dissociative symptoms mediated the small relation of trauma load in childhood and positive symptoms. The role of trauma and ACE on psychotic symptoms can be specified by neglect during frontocortical development in the exacerbation of positive symptoms. The mediating role of dissociation is restricted to the relation of childhood trauma and positive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Funnel-web spider bite: a systematic review of recorded clinical cases.

PubMed

Isbister, Geoffrey K; Gray, Michael R; Balit, Corrine R; Raven, Robert J; Stokes, Barrie J; Porges, Kate; Tankel, Alan S; Turner, Elizabeth; White, Julian; Fisher, Malcolm McD

2005-04-18

To investigate species-specific envenoming rates and spectrum of severity of funnel-web spider bites, and the efficacy and adverse effects of funnel-web spider antivenom. Cases were identified from a prospective study of spider bite presenting to four major hospitals and three state poisons information centres (1999-2003); museum records of spider specimens since 1926; NSW Poisons Information Centre database; MEDLINE and EMBASE search; clinical toxinology textbooks; the media; and the manufacturer's reports of antivenom use. Patient age and sex, geographical location, month, expert identification of the spider, clinical effects and management; envenoming was classified as severe, mild-moderate or minor/local effects. 198 potential funnel-web spider bites were identified: 138 were definite (spider expertly identified to species or genus), and 77 produced severe envenoming. All species-identified severe cases were attributed to one of six species restricted to NSW and southern Queensland. Rates of severe envenoming were: Hadronyche cerberea (75%), H. formidabilis (63%), Atrax robustus (17%), Hadronyche sp. 14 (17%), H. infensa (14%) and H. versuta (11%). Antivenom was used in 75 patients, including 22 children (median dose, 3 ampoules; range, 1-17), with a complete response in 97% of expertly identified cases. Three adverse reactions were reported, all in adults: two early allergic reactions (one mild and one with severe systemic effects requiring adrenaline), and one case of serum sickness. Severe funnel-web spider envenoming is confined to NSW and southern Queensland; tree-dwelling funnel webs (H. cerberea and H. formidabilis) have the highest envenoming rates. Funnel-web spider antivenom appears effective and safe; severe allergic reactions are uncommon.

Responsiveness of the quality of life in late-stage dementia scale to psychotropic drug treatment in late-stage dementia.

PubMed

Martin-Cook, Kristin; Hynan, Linda S; Rice-Koch, Kathleen; Svetlik, Doris A; Weiner, Myron F

2005-01-01

We report on the responsiveness of a previously validated quality-of-life scale, the Quality of Life in Late-Stage Dementia scale (QUALID), as an outcome measure in a clinical trial of two psychotropic medications. Secondary analyses were conducted comparing outcome measures used in a randomized double-blind trial of two antipsychotics (olanzapine and risperidone) for the treatment of dementia-related behavioral symptoms. The QUALID was completed for 31 of the patients in addition to several measures of behavior-related dementia symptoms including the Neuropsychiatric Inventory, the Withdrawn Behavior subscale of the Multidimensional Observation Scale for Elderly Subjects, the Mini-Mental State Examination, and the Clinical Global Impression. Measures of safety and adverse effects included the Simpson-Angus Scale and records of specific adverse events. A significant positive relationship was found between QUALID score and improvement in behavioral symptoms, and a negative association was found with adverse medication effects. The QUALID was sensitive to both the treatment effects and the adverse effects of medication in this sample of patients.

Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

PubMed

Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

2014-01-01

Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations.

PubMed

Granata, Vincenza; Cascella, Marco; Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo; Petrillo, Antonella

2016-01-01

Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

PubMed

Donovan, Kristine A; Walker, Lauren M; Wassersug, Richard J; Thompson, Lora M A; Robinson, John W

2015-12-15

The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. © 2015 American Cancer Society.

Effects of Personality Disorder and Other Variables on Professionals' Evaluation of Treatment Features in Individuals with Mild Intellectual Disabilities and Severe Behavior Problems

ERIC Educational Resources Information Center

van den Hazel, Teunis; Didden, Robert; Korzilius, Hubert

2009-01-01

The diagnosis personality disorder is often found among samples of adults with mild intellectual disability and severe behavioral and mental health disorders. The number of studies on the adverse effects of this diagnosis are scarce. Using vignettes in the present study, we have explored the relationship between the diagnosis personality disorder…

Antimalarial drugs for rheumatoid disease during pregnancy.

PubMed Central

Koren, G.

1999-01-01

QUESTION: One of my patients, who has rheumatoid arthritis, has just found out she is pregnant. She is being treated with hydroxychloroquine. I could not find anything about the safety of this drug during pregnancy. ANSWER: Most of the literature on this drug relates to prophylaxis for malaria. Much lower doses than those used for rheumatic diseases are given with no adverse fetal effects. Several studies on use of the drug for rheumatic diseases during pregnancy also failed to show adverse fetal effects, although, in most cases, only first-trimester exposure was reported. PMID:10626050

Evolution of a Planar Wake in Adverse Pressure Gradient

NASA Technical Reports Server (NTRS)

Driver, David M.; Mateer, George G.

2016-01-01

In the interest of improving the predictability of high-lift systems at maximum lift conditions, a series of fundamental experiments were conducted to study the effects of adverse pressure gradient on a wake flow. Mean and fluctuating velocities were measured with a two-component laser-Doppler velocimeter. Data were obtained for several cases of adverse pressure gradient, producing flows ranging from no reversed flow to massively reversed flow. While the turbulent Reynolds stresses increase with increasing size of the reversed flow region, the gradient of Reynolds stress does not. Computations using various turbulence models were unable to reproduce the reversed flow.

Mania and Psychosis Associated with St. John's Wort and Ginseng

PubMed Central

Faubion, Matthew D.

2005-01-01

The use of complimentary/alternative medicine has become popular as evidenced by grocery store aisles and “infomercials” devoted to herbal products. These products are often misconstrued as safe because of their natural origin. With an increase in the consumption of these products, physicians need to be aware of their potential adverse effects. There are several popular over-the-counter herbal products that can affect one's behavior, especially resulting in acute mania and/or psychosis. This article provides an overview of existing literature regarding the increased use of herbal agents, reviews several case reports describing a potential association between herbal products (St. John's Wort and ginseng) and the development of mania and psychosis, and discusses the limitations in determining the frequency of serious adverse effects due to herbal products. PMID:21120109

Using Portable Samplers to Determine the Effect of Roadside Vegetation on Near-Road Air Quality

EPA Science Inventory

Growing evidence exists that populations spending significant amounts of time near major roads face increased risks for several adverse health effects.1 These effects may be attributable to increased exposure to particulate matter (PM), gaseous criteria pollutants, and air toxic...

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

PubMed

Comhair, Suzy A A; Gaston, Benjamin M; Ricci, Kristin S; Hammel, Jeffrey; Dweik, Raed A; Teague, W Gerald; Meyers, Deborah; Ampleford, Elizabeth J; Bleecker, Eugene R; Busse, William W; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Israel, Elliot; Jarjour, W Nizar; Moore, Wendy; Peters, Stephen P; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2011-05-04

Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

PubMed Central

Li, Qingfeng

2016-01-01

Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

PubMed Central

Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Xu, Shifen

2015-01-01

As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

PubMed

Lieberman, Harris R; Tharion, William J; Shukitt-Hale, Barbara; Speckman, Karen L; Tulley, Richard

2002-11-01

When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

PubMed Central

Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

2016-01-01

Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

Propulsion integration for military aircraft

NASA Technical Reports Server (NTRS)

Henderson, William P.

1989-01-01

The transonic aerodynamic characteristics for high-performance aircraft are significantly affected by shock-induced flow interactions as well as other local flow interference effects which usually occur at transonic speeds. These adverse interactions can not only cause high drag, but can cause unusual aerodynamic loadings and/or severe stability and control problems. Many new programs are underway to develop methods for reducing the adverse effects, as well as to develop an understanding of the basic flow conditions which are the primary contributors. It is anticipated that these new programs will result in technologies which can reduce the aircraft cruise drag through improved integration as well as increased aircraft maneuverability throughh the application of thrust vectoring. This paper will identify some of the primary propulsion integration problems for high performance aircraft at transonic speeds, and demonstrate several methods for reducing or eliminating the undesirable characteristics, while enhancing configuration effectiveness.

Rational use of calcium-channel antagonists in Raynaud's phenomenon.

PubMed

Sturgill, M G; Seibold, J R

1998-11-01

Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

Adapting Buildings for Indoor Air Quality in a Changing Climate

EPA Pesticide Factsheets

Climate change presents many challenges, including the production of severe weather events. These events and efforts to minimize their effects through weatherization can adversely affect indoor environments.

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

PubMed

Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

2016-03-01

The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43). For low-risk pregnancies, there was no significant difference in the levels for any of the measured indices over the study period (P = .61, P = .41, and P = .34 for the Modified Adverse Outcomes Index, Modified Weighted Adverse Outcomes Index, and Modified Severity Index, respectively). Among the high-risk pregnancies, the monthly Modified Weighted Adverse Outcomes Index decreased by 4.2 ± 1.8 (P = .03). The monthly Modified Severity Index decreased by 53.9 ± 17.7 points from the pre- to the postintervention periods (P = .01) and was < 50% of the predicted Modified Severity Index had the intervention not been implemented. The cesarean delivery rate was increasing prior to the intervention, but the rate was stable after the intervention, and the absolute rate did not differ between the pre- and the postintervention periods (28.4% vs 30.0%, P = .20). Overall and for high-risk pregnancies, the implementation of the labor and delivery care bundle had a positive impact on the Modified Weighted Adverse Outcomes Index and Modified Severity Index but not the Modified Adverse Outcomes Index. Copyright © 2016 Elsevier Inc. All rights reserved.

Tofacitinib for the treatment of alopecia areata and variants in adolescents.

PubMed

Craiglow, Brittany G; Liu, Lucy Y; King, Brett A

2017-01-01

There are no reliably effective therapies for alopecia areata (AA). We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA. We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems. Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild. Limitations include the retrospective nature of the data, small sample size, and lack of a control group. Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis.

PubMed

Min, Le; Hodi, F Stephen

2014-01-01

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. ©2014 AACR.

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

PubMed

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

2016-01-01

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

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study – PRIME study

PubMed Central

Shah, Kshitij; Chaudhari, Omvijay B; Gupta, Palash; Chaudhuri, R Hom; Kamilya, Ranjan; Kulkarni, Shreedhar S; Subbaiah, S; Sorathia, Zubair H; Billa, Gauri

2017-01-01

Objective To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician’s routine clinical practice. Materials and methods In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18–60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. Results A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as “very good to good”, whereas according to physician’s assessment, “very good to good” tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. Conclusion Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions. PMID:28579825

β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia

PubMed Central

Bohn, Laura M.

2016-01-01

Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843

What is the role of steroids in pneumonia therapy?

PubMed

Póvoa, Pedro; Salluh, Jorge I F

2012-04-01

This review evaluates the potential benefits as well as adverse effects from adjunctive therapy with systemic steroids in patients with pneumonia: either mild-to-moderate or severe, community-acquired or hospital-acquired, of bacterial or of viral origin (in particular H1N1 viral infection). Steroids potentially modulate the marked and persistent activation of the immune system in pneumonia. However, several recent randomized controlled trials and large prospective observational studies have repeatedly shown that steroids had no impact on survival, the clinical event of interest, but in severe pneumonia some studies pointed to potential harmful effect. In addition, adverse effects, namely hyperglycemia, superinfections, as well as increased length-of-stay, were frequent findings in the steroid-treated patients. According to the current evidence, there are no data to support the well tolerated use of systemic steroids as a standard of care in pneumonia, neither in mild-to-moderate and severe, nor in bacterial and viral infection. Clinical and basic research should work together to improve trial designs to identify reliable surrogate markers of outcome, in particular of mortality. This may improve the patient selection and facilitate the identification of subgroups that can benefit from adjunctive steroid therapy.

A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris.

PubMed

Dong, Yiyun; Zhou, Guoyu; Chen, Jinan; Shen, Lingyue; Jianxin, Zhao; Xu, Qing; Zhu, Yulan

2016-03-01

This study investigated the efficacy and safety of a newly designed LED device used in photodiagnosis and photodynamic therapy of moderate to severe acne vulgaris in Chinese patients. Forty-six patients with moderate to severe facial acne showing high degrees of fluorescence by ultraviolet light examination were illuminated during ALA-PDT with two wavelengths of light (543-548 nm, and 630±6 nm, respectively) after 2 h of incubation with ALA. Each patient received treatment once every 30 days for two or three sessions. Two independent investigators assigned an acne severity score at baseline, one week after each treatment, as well as 4, 8, and 12 weeks after the completion of treatment. Adverse effects were recorded during and after each treatment. All patients rated their satisfaction with the results of treatment at a 12-week follow up visit. The ALA-PDL treatment regimen showed an overall effectiveness rate of 89.13% (41/46 patients). Some degree of clinical efficacy was seen in 71.42%, 86.67%, and 95.83% of patients with grades IV, V, and VI acne, respectively, and the rate of clinical effectiveness increased with increasing acne severity. When compared with baseline scores, significant reductions in acne scores were obtained at 8, and 12 weeks after completion of treatment. Maximum efficacy was shown at the 12 week follow up. No severe adverse events were observed. ALA-PDT administered with the newly designed LED device was an effective treatment for moderate to severe acne vulgaris, and side effects were mild and reversible. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 13252 - Pyroxasulfone; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... one of the following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the... relationship of the results of the studies to human risk. EPA has also considered available information... adverse effects in several target organs. Effects seen in animal studies included cardiac toxicity...

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

PubMed Central

Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

2018-01-01

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies. PMID:29605975

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use.

PubMed

Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

2018-04-30

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

Economic Adversity Transitions From Childhood to Older Adulthood Are Differentially Associated With Later-Life Physical Performance Measures in Men and Women in Middle and High-Income Sites.

PubMed

Hwang, Phoebe W; Dos Santos Gomes, Cristiano; Auais, Mohammad; Braun, Kathryn L; Guralnik, Jack M; Pirkle, Catherine M

2017-10-01

This study examines the relationship between economic adversity transitions from childhood to older adulthood and older adulthood physical performance among 1,998 community-dwelling older adults from five demographically diverse sites from middle and high-income countries. The principal exposure variable was economic adversity transition. No adversity encompassed not experiencing poverty in both childhood and older adulthood, improved described having only experienced poverty in childhood, worsened captured having experienced poverty in older adulthood, and severe is having experienced poverty in both childhood and older adulthood. The short physical performance battery (SPPB) was used for outcome measures. Analyses of the continuous SPPB score used linear regression, while analysis of a binary outcome (SPPB < 8 vs. ≥8) used Poisson regression models with robust error variance, both adjusting for sex, education, and site location. In sex-stratified models, the SPPB < 8 prevalence rate ratio (PRR) was higher for the severe (PRR: 2.80, 95% confidence interval [CI] = [1.70, 4.61]), worsened (PRR: 2.40, 95% CI = [1.41, 4.09]), and improved (PRR: 1.82, 95% CI = [1.11, 3.01]) groups, compared with those with no adversity in childhood or as adults, but only for females. Findings from this study indicate that persistent economic adversity has a negative effect on older adult physical performance, especially among women.

Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.

PubMed

Halbreich, Uriel; Kahn, Linda S

2003-11-01

Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

Medication errors: the role of the patient.

PubMed

Britten, Nicky

2009-06-01

1. Patients and their carers will usually be the first to notice any observable problems resulting from medication errors. They will probably be unable to distinguish between medication errors, adverse drug reactions, or 'side effects'. 2. Little is known about how patients understand drug related problems or how they make attributions of adverse effects. Some research suggests that patients' cognitive models of adverse drug reactions bear a close relationship to models of illness perception. 3. Attributions of adverse drug reactions are related to people's previous experiences and to their level of education. The evidence suggests that on the whole patients' reports of adverse drug reactions are accurate. However, patients do not report all the problems they perceive and are more likely to report those that they do perceive as severe. Patients may not report problems attributed to their medications if they are fearful of doctors' reactions. Doctors may respond inappropriately to patients' concerns, for example by ignoring them. Some authors have proposed the use of a symptom checklist to elicit patients' reports of suspected adverse drug reactions. 4. Many patients want information about adverse drug effects, and the challenge for the professional is to judge how much information to provide and the best way of doing so. Professionals' inappropriate emphasis on adherence may be dangerous when a medication error has occurred. 5. Recent NICE guidelines recommend that professionals should ask patients if they have any concerns about their medicines, and this approach is likely to yield information conducive to the identification of medication errors.

Subjective Effects, Misuse, and Adverse Effects of Osmotic-Release Methylphenidate Treatment in Adolescent Substance Abusers with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Lewis, Daniel F.; Riggs, Paula D.; Davies, Robert D.; Adler, Lenard A.; Sonne, Susan; Somoza, Eugene C.

2011-01-01

Abstract Objective Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non–substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Method Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13–18) with at least one non-nicotine SUD and one with 255 adult smokers (18–55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Results Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. Conclusions With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence. PMID:22040190

Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder.

PubMed

Winhusen, Theresa M; Lewis, Daniel F; Riggs, Paula D; Davies, Robert D; Adler, Lenard A; Sonne, Susan; Somoza, Eugene C

2011-10-01

Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence.

Use of Nonopioid Analgesics and the Impact on Patient Outcomes.

PubMed

Sanzone, Anthony G

2016-05-01

Although opioids are widely used for the management of pain in patients with hip fracture, these medications are known to have a wide range of adverse effects that can result in suboptimal outcomes or serious life-threatening complications. Common opioid-related adverse events include gastrointestinal effects, central nervous system effects, and respiratory depression. Hip fractures occur most frequently among the elderly-the very population that is most susceptible to the adverse effects of opioids and the risks of serious physiological complications. There has been much interest during recent years in identifying alternative analgesic approaches that are less opioid-dependent. There is good evidence to show that nerve blocks can be effective in managing the acute pain associated with hip fracture. However, sciatic and femoral nerve blocks seem to increase the risk of several clinically significant adverse events. A retrospective cohort study that examined the effectiveness of scheduled intravenous acetaminophen as part of the pain management protocol for hip fracture patients revealed significant improvement in pain scores, narcotic use, length of stay, and missed physical therapy sessions. Limited data exist in patients with hip fracture on the effects of infiltration of the surgical site with the local anesthetic agent, bupivacaine. However, extensive use of bupivacaine in hip arthroplasty surgery suggests that it may be highly beneficial in the patient with hip fracture.

Mining adverse drug reactions from online healthcare forums using hidden Markov model.

PubMed

Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

2014-10-23

Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also identified. The results from the HMM based Text Miner are encouraging to pursue further enhancements to this approach. The mined novel side-effects can act as early indicators for health authorities to help focus their efforts in post-marketing drug surveillance.

The household food insecurity gradient and potential reductions in adverse population mental health outcomes in Canadian adults.

PubMed

Jessiman-Perreault, Geneviève; McIntyre, Lynn

2017-12-01

Household food insecurity is related to poor mental health. This study examines whether the level of household food insecurity is associated with a gradient in the risk of reporting six adverse mental health outcomes. This study further quantifies the mental health impact if severe food insecurity, the extreme of the risk continuum, were eliminated in Canada. Using a pooled sample of the Canadian Community Health Survey (N = 302,683), we examined the relationship between level of food insecurity, in adults 18-64 years, and reporting six adverse mental health outcomes. We conducted a probit analysis adjusted for multi-variable models, to calculate the reduction in the odds of reporting mental health outcomes that might accrue from the elimination of severe food insecurity. Controlling for various demographic and socioeconomic covariates, a food insecurity gradient was found in six mental health outcomes. We calculated that a decrease between 8.1% and 16.0% in the reporting of these mental health outcomes would accrue if those who are currently severely food insecure became food secure, after controlling for covariates. Household food insecurity has a pervasive graded negative effect on a variety of mental health outcomes, in which significantly higher levels of food insecurity are associated with a higher risk of adverse mental health outcomes. Reduction of food insecurity, particularly at the severe level, is a public health concern and a modifiable structural determinant of health worthy of macro-level policy intervention.

Antidepressant-Induced Female Sexual Dysfunction.

PubMed

Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

2016-09-01

Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report.

PubMed

Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects. Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain.

Compliance, Safety, and Effectiveness of Fixed-Dose Artesunate-Amodiaquine for Presumptive Treatment of Non-Severe Malaria in the Context of Home Management of Malaria in Madagascar

PubMed Central

Ratsimbasoa, Arsène; Ravony, Harintsoa; Vonimpaisomihanta, Jeanne-Aimée; Raherinjafy, Rogelin; Jahevitra, Martial; Rapelanoro, Rabenja; Rakotomanga, Jean De Dieu Marie; Malvy, Denis; Millet, Pascal; Ménard, Didier

2012-01-01

Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria. PMID:22302849

Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality

PubMed Central

Di Lorenzo, Chiara; Ceschi, Alessandro; Kupferschmidt, Hugo; Lüde, Saskia; De Souza Nascimento, Elizabeth; Dos Santos, Ariana; Colombo, Francesca; Frigerio, Gianfranco; Nørby, Karin; Plumb, Jenny; Finglas, Paul; Restani, Patrizia

2015-01-01

AIMS The objective of this review was to collect available data on the following: (i) adverse effects observed in humans from the intake of plant food supplements or botanical preparations; (ii) the misidentification of poisonous plants; and (iii) interactions between plant food supplements/botanicals and conventional drugs or nutrients. METHODS PubMed/MEDLINE and Embase were searched from database inception to June 2014, using the terms ‘adverse effect/s’, ‘poisoning/s’, ‘plant food supplement/s’, ‘misidentification/s’ and ‘interaction/s’ in combination with the relevant plant name. All papers were critically evaluated according to the World Health Organization Guidelines for causality assessment. RESULTS Data were obtained for 66 plants that are common ingredients of plant food supplements; of the 492 papers selected, 402 (81.7%) dealt with adverse effects directly associated with the botanical and 89 (18.1%) concerned interactions with conventional drugs. Only one case was associated with misidentification. Adverse effects were reported for 39 of the 66 botanical substances searched. Of the total references, 86.6% were associated with 14 plants, including Glycine max/soybean (19.3%), Glycyrrhiza glabra/liquorice (12.2%), Camellia sinensis/green tea ( 8.7%) and Ginkgo biloba/gingko (8.5%). CONCLUSIONS Considering the length of time examined and the number of plants included in the review, it is remarkable that: (i) the adverse effects due to botanical ingredients were relatively infrequent, if assessed for causality; and (ii) the number of severe clinical reactions was very limited, but some fatal cases have been described. Data presented in this review were assessed for quality in order to make the results maximally useful for clinicians in identifying or excluding deleterious effects of botanicals. PMID:25251944

Quantitative weight of evidence assessment of higher tier studies on the toxicity and risks of neonicotinoids in honeybees. 4. Thiamethoxam.

PubMed

Stephenson, Gladys L; Solomon, Keith R

2017-01-01

A quantitative weight of evidence (QWoE) methodology was used to assess several higher-tier studies on the effects of thiamethoxam (TMX) on honeybees. Assessment endpoints were population size and viability of commercially managed honeybee colonies and quantity of hive products. A higher-tier field toxicology study indicated a no-observed-adverse effect concentration (NOAEC) of 29.5 µg TMX/kg syrup, equivalent to an oral no-observed-adverse-effect-dose (NOAED) of 8.6 ng/bee/day for all responses measured. For exposures via deposition of dust, a conservative no-observed-adverse-effect-rate at the level of the colony was 0.1 g TMX/ha. There was minimal risk to honeybees from exposure to TMX via nectar and pollen from its use as a seed-treatment. For exposures via dust and dust/seed applications, there were no concentrations above the risk values for TMX in nectar and pollen. Although some risks were identified for potential exposures via guttation fluid, this route of exposure is incomplete; no apparent adverse effects were observed in field studies. For exposures via dust/seed and dust/foliar applications, few adverse effects were observed. Considering all lines of evidence, the quality of the studies included in this analysis was variable. However, the results of the studies were consistent and point to the same conclusion. The overall weight of evidence based on many studies indicates that TMX has no adverse effects on viability or survival of the colony. Thus, the overall conclusion is that the treatment of seeds with thiamethoxam, as currently used in good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

PubMed

Kularatne, Senanayake A M; Weerakoon, Kosala; Silva, Anjana; Maduwage, Kalana; Walathara, Chamara; Rathnayake, Ishani; Medagedara, Senal; Paranagama, Ranjith; Mendis, Suresh; Kumarasiri, P V R

2016-09-15

The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the timing, rate or severity of adverse drug reactions to antivenom when administered simultaneously and up to 4 h prior to antivenom. Copyright © 2016 Elsevier Ltd. All rights reserved.

Moderate Childhood Stress Buffers Against Depressive Response to Proximal Stressors: A Multi-Wave Prospective Study of Early Adolescents

PubMed Central

Shapero, Benjamin G.; Hamilton, Jessica L.; Stange, Jonathan P.; Liu, Richard T.; Y.Abramson, Lyn; Alloy, Lauren B.

2015-01-01

Although the majority of research in the field has focused on childhood stressors as a risk factor for psychopathology, a burgeoning body of literature has focused on the possible steeling effect of moderate types of stressful events. The current study investigated the effects of proximal life stressors on prospective changes in depressive symptoms, and whether a history of moderate childhood adversity would moderate this relationship in a multi-wave study of a diverse community sample of early adolescents (N = 163, 52% female, 51% Caucasian). Hierarchical linear modeling was run with four waves of data. Adolescents with greater moderately severe early life events evinced a blunted depressive symptom response to changes in proximal stressful events in the previous 9 months, compared to those with fewer early moderately severe experiences of adversity. These results held after controlling for between-subject factors such as race, gender, severe early life stress, and average stress over the four waves of data. Findings indicate that greater exposure to moderate childhood stressors may buffer against the negative effects of subsequent stressors, suggesting the importance of a nuanced developmental approach to studying the effects of early life stress. PMID:25911194

Recurrence of Panic Attacks after Influenza Vaccination: Two Case Reports.

PubMed

Kim, Han-Joon; Jeon, Sang-Won; Yoon, Ho-Kyoung

2016-11-30

Human influenza is a contagious respiratory illness caused by the influenza virus. The influenza vaccination is recommended annually, but several adverse effects related to allergic reactions have been reported. Panic attacks are also known to occur, but no case of a panic attack adverse effect has been reported in South Korea. We present two cases of panic disorder patients whose symptoms were aggravated by the influenza vaccination. We assumed that dysregulation of T-lymphocytes in panic disorder patients could have a role in activating various kinds of cytokines and chemokines, which then can lead to panic attack aggravation.

[Research advances in pharmacogenomics of mercaptopurine].

PubMed

Chen, Xiao-Xiao; Shen, Shu-Hong

2017-09-01

Mercaptopurine is a common chemotherapeutic drug and immunosuppressive agent and plays an important role in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. It may cause severe adverse effects such as myelosuppression, which may result in the interruption of treatment or complications including infection or even threaten patients' lives. However, the adverse effects of mercaptopurine show significant racial and individual differences, which reveal the important role of genetic diversity. Recent research advances in pharmacogenomics have gradually revealed the genetic nature of such differences. This article reviews the recent research advances in the pharmacogenomics and individualized application of mercaptopurine.

Detailed assessments of childhood adversity enhance prediction of central obesity independent of gender, race, adult psychosocial risk and health behaviors.

PubMed

Davis, Cynthia R; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S; Crowell, Judith A

2014-02-01

This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of "modifiable" risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities × severity × chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. 210 Black/African Americans and White/European Americans, mean age=45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. © 2013.

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

PubMed Central

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

2010-01-01

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

Does the Size of the Effect of Adverse Events at High Ages on Daily-Life Physical Functioning Depend on the Economic Conditions Around Birth?

PubMed

Scholte, Robert; van den Berg, Gerard J; Lindeboom, Maarten; Deeg, Dorly J H

2017-01-01

This paper considers determinants of physical functional limitations in daily-life activities at high ages. Specifically, we quantify the extent to which the impact of adverse life events on this outcome is larger in case of exposure to adverse economic conditions early in life. Adverse life events include bereavement, severe illness in the family, and the onset of chronic diseases. We use a longitudinal data set of individuals born in the first decades of the 20th century. The business cycle around birth is used as an indicator of economic conditions early in life. We find that the extent to which functional limitations suffer from the onset of chronic diseases is larger if the individual was born in a recession. The long-run effect of economic conditions early in life on functional limitations at high ages runs primarily via this life event. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Long-term adverse effects of neonatal exposure to bisphenol A on the murine female reproductive tract.

PubMed

Newbold, Retha R; Jefferson, Wendy N; Padilla-Banks, Elizabeth

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 microg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation.

Long-term Adverse Effects of Neonatal Exposure to Bisphenol A on the Murine Female Reproductive Tract

PubMed Central

Newbold, Retha R.; Jefferson, Wendy N.; Banks, Elizabeth Padilla

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 μg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation. PMID:17804194

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

PubMed

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

2018-06-01

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

Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease.

PubMed

Bakker, Jaap A; Drent, Marjolein; Bierau, Jörgen

2007-09-01

Mercaptopurine therapy is increasingly important as immunosuppressive therapy in interstitial lung disease. We focus on human mercaptopurine metabolism and the defects in this metabolism causing adverse drug reactions. Defects in mercaptopurine metabolizing enzymes like thiopurine methyltransferase and inosine triphosphate pyrophosphohydrolase lead to severe adverse drug reactions, sometimes with fatal outcome. Other enzymes, still not thoroughly investigated, can give rise to toxic effects or decreased efficacy in mercaptopurine therapy when the activity of these enzymes is altered. Pharmacogenetic screening of potential patients for mercaptopurine therapy is important to avoid adverse drug reactions caused by inherited enzyme deficiencies in these metabolic pathways. Pretreatment screening for deficiencies of mercaptopurine metabolizing enzymes will significantly reduce the number of patients with an adverse drug reaction and concomitantly associated healthcare costs.

Safety of statins.

PubMed

Brown, William Virgil

2008-12-01

To examine the evidence for the adverse effects that have been reported during the use of statins. We now have over twenty years of prescription use and many large well controlled trials with statin therapy for hypercholesterolemia. There is only one significant and well documented adverse effect with this group of drugs, rhabdomyolysis. Significant muscle damage is very rare when statin therapy is used in patients carefully screened for concomitant use of other drugs which may interfere with statin catabolism and excretion. Patients with severely impaired liver function are also at risk due to the importance of hepatic excretion of all statins. Chronic myalgias or other pain syndromes have not been confirmed by blinded placebo controlled trials. A significant and reproducible rise in liver enzymes (alanine and aspartate aminotransferases) is observed in 1 to 3% of patients but actual liver damage may not occur at all. Benign and transient proteinuria occurs without evidence of altered renal function. Creatinine clearance is usually increased by statins. Peripheral neuropathy may be a rare adverse effect and this needs further study. Statins are very effective at reducing the incidence of myocardial infarction, stroke and other manifestations of vascular disease. The adverse event rates are very uncommon and the benefit risk ratio is extremely high.

Root Cause Analysis: Learning from Adverse Safety Events.

PubMed

Brook, Olga R; Kruskal, Jonathan B; Eisenberg, Ronald L; Larson, David B

2015-10-01

Serious adverse events continue to occur in clinical practice, despite our best preventive efforts. It is essential that radiologists, both as individuals and as a part of organizations, learn from such events and make appropriate changes to decrease the likelihood that such events will recur. Root cause analysis (RCA) is a process to (a) identify factors that underlie variation in performance or that predispose an event toward undesired outcomes and (b) allow for development of effective strategies to decrease the likelihood of similar adverse events occurring in the future. An RCA process should be performed within the environment of a culture of safety, focusing on underlying system contributors and, in a confidential manner, taking into account the emotional effects on the staff involved. The Joint Commission now requires that a credible RCA be performed within 45 days for all sentinel or major adverse events, emphasizing the need for all radiologists to understand the processes with which an effective RCA can be performed. Several RCA-related tools that have been found to be useful in the radiology setting include the "five whys" approach to determine causation; cause-and-effect, or Ishikawa, diagrams; causal tree mapping; affinity diagrams; and Pareto charts. © RSNA, 2015.

Crisis to Catalyst: The Strategic Effects of the Somalia Affair on the Canadian Armed Forces

DTIC Science & Technology

adversely impacted the professional autonomy of the military, and forced an unprecedented evolution of the Canadian officer corps. Following a detailed...effects. Focus subsequently turns to the principle strategic effects and their continued impact on the CAF and the society it serves. In conclusion, several implications are discussed.

Acute generalized exanthematous pustulosis associated with terbinafine: a case report.

PubMed

Turan, Hakan; Acer, Ersoy; Erdem, Havva; Uslu, Esma; Aliagaoglu, Cihangir

2013-10-01

A 27-year-old male patient who has used oral terbinafine for two weeks was admitted to our outpatient clinic for non-follicular millimetric pustules on erythematous and edematous different-sized plaques on his trunk and flexural areas. He was diagnosed with acute generalized exanthematous pustulosis (AGEP) because of terbinafine use in the light of history, clinical and histopathological findings. An AGEP is a rare and severe pustular reaction usually triggered by systemic drug intake. Approximately, 2.3% of the patients having oral terbinafine have been reported to develop cutaneous adverse effects. Although terbinafine is a commonly used medicine, it must be considered that it may cause severe adverse reactions.

"Freshman's week": characteristics associated with participation and experiencing adverse effects.

PubMed

Erevik, E K; Pallesen, S; Vedaa, Ø; Andreassen, C S; Torsheim, T

2018-05-29

"Freshman's week" (FW) is a Norwegian initiation ritual to higher education. Previous research has suggested that FW-participation is associated with better social adjustment to the student setting, as well as heavy alcohol use both during and after the event. In this study, we aimed to identify characteristics associated with participation in FW and characteristics associated with experiencing adverse effects of alcohol use during FW. Students in the city of Bergen, Norway participated in a survey during fall 2015, shortly after FW. The current sample consisted of the first-year students (N = 4, 401, estimated response rate: 49%). The sample's mean age was 24 years (range: 17-73 years), 65% were females, and the majority were born in Norway (93%). Logistic regressions were conducted to identify characteristics associated with participation in FW and experiencing adverse effects. A total of 64% of the first-year students reported participation in FW, and 27% of these reported experiencing at least one adverse alcohol-related effect during FW. Participation in FW was positively associated with being single (OR = 1.29), extroversion (OR = 1.18), and alcohol use (OR = 1.28), and inversely associated with age (OR = 0.70), and having children (OR = 0.36). Several characteristics (e.g., alcohol use (OR = 1.84), extroversion (OR = 0.60), symptoms of depression (OR = 1.60)) were associated with an increased risk of experiencing adverse effects of alcohol use during participation. The current results suggest that initiatives for increasing the participation rate in FW, reducing alcohol use during FW, and decreasing the occurrence of adverse alcohol effects during FW are warranted. Aiming to reduce the focus on alcohol use during FW, and seeking to make FW more available and enjoyable for students with other priorities, students who do not match the stereotype of the typical first-year student, and less sociable students, might both increase participation rate and prevent the occurrence of adverse alcohol effects. Future studies should aim to develop and assess interventions designed to increase participation in FW and reduce the occurrence of adverse effects related to participation.

Systematic review of pediatric health outcomes associated with childhood adversity.

PubMed

Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

2018-02-23

Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better understand how adversity, its timing and severity, and the presence of individual genetic, epigenetic, and protective factors affects children's health and development.

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

PubMed

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

2016-12-15

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

The Vise/Vice of Standardized Testing: National Depreciation by Quantification.

ERIC Educational Resources Information Center

Farrell, Edmund J.

Current uses of standardized English tests are adversely affecting students, misleading lay people, and having a pernicious effect on the English profession. These tests are severely limited, incapable of assessing speaking skill and effectiveness, reading interests, appreciation of literature, listening skill, understanding and appreciation of…

Patient Safety Learning Laboratory: Making Acute Care More Patient-Centered

ClinicalTrials.gov

2017-03-22

Central Line-Associated Bloodstream Infection (CLABSI); Venous Thromboembolism; Patient Fall; Catheter-Associated Infection; Severe Hypoglycemia; Opioid-Related Severe Adverse Drug Event; Hospital Acquired Pressure Ulcer; Adverse Drug Event; Severe Hospital Acquired Delerium; Rapid Response Related to Arrhythmia

Testing a Theoretical Model of Perceived Self-Efficacy for Cancer-Related Fatigue Self-Management and Optimal Physical Functional Status

PubMed Central

Hoffman, Amy J.; von Eye, Alexander; Gift, Audrey G.; Given, Barbara A.; Given, Charles W.; Rothert, Marilyn

2009-01-01

Background Critical gaps exist in the understanding of cancer symptoms, particularly for cancer-related fatigue (CRF). Existing theories and models do not examine the key role perceived self-efficacy (PSE) plays in a person's ability to manage symptoms. Objectives To test the hypothesis that physical functional status (PFS) is predicted through patient characteristics, CRF, other symptoms, and PSE for fatigue self-management in persons with cancer. Methods This study is a secondary data analysis from the baseline observation of two randomized control trials. The combined data set includes 298 subjects who were undergoing a course of chemotherapy. Key variables included physiological and contextual patient characteristics, the severity from CRF and other symptoms, PSE, and PFS. Path analysis examined the relationships among the variables in the proposed theoretical model. Results Persons with cancer reported CRF as the most prevalent symptom among a mean of 7.4 other concurrent symptoms. The severity from CRF had a direct and indirect effect on PFS, with CRF having a direct adverse impact on PFS (t = -7.02) and an indirect adverse effect as part of the severity from the other symptoms (t = 9.69) which also adversely impacted PFS (t = -2.71). Consistent with the proposed theoretical model, PSE had a positive effect on the PFS (t = 2.87) of persons with cancer while serving as a mediator between CRF severity and PFS. Discussion Cancer-related fatigure is prevalent and related to the presence of other symptoms, and PSE for fatigue self-management is an important factor influencing CRF and PFS. A foundation is provided for future intervention studies to increase PSE to achieve optimal PFS in persons with cancer. PMID:19092553

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

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

Dijk, Irma W.E.M. van, E-mail: i.w.vandijk@amc.uva.nl; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 yearsmore » after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.« less

Testing an explanatory model of nurses' intention to report adverse drug reactions in hospital settings.

PubMed

Angelis, Alessia De; Pancani, Luca; Steca, Patrizia; Colaceci, Sofia; Giusti, Angela; Tibaldi, Laura; Alvaro, Rosaria; Ausili, Davide; Vellone, Ercole

2017-05-01

To test an explanatory model of nurses' intention to report adverse drug reactions in hospital settings, based on the theory of planned behaviour. Under-reporting of adverse drug reactions is an important problem among nurses. A cross-sectional design was used. Data were collected with the adverse drug reporting nurses' questionnaire. Confirmatory factor analysis was performed to test the factor validity of the adverse drug reporting nurses' questionnaire, and structural equation modelling was used to test the explanatory model. The convenience sample comprised 500 Italian hospital nurses (mean age = 43.52). Confirmatory factor analysis supported the factor validity of the adverse drug reporting nurses' questionnaire. The structural equation modelling showed a good fit with the data. Nurses' intention to report adverse drug reactions was significantly predicted by attitudes, subjective norms and perceived behavioural control (R² = 0.16). The theory of planned behaviour effectively explained the mechanisms behind nurses' intention to report adverse drug reactions, showing how several factors come into play. In a scenario of organisational empowerment towards adverse drug reaction reporting, the major predictors of the intention to report are support for the decision to report adverse drug reactions from other health care practitioners, perceptions about the value of adverse drug reaction reporting and nurses' favourable self-assessment of their adverse drug reaction reporting skills. © 2017 John Wiley & Sons Ltd.

Sampling and Analysis of Emerging Pollutants

EPA Science Inventory

Historically, environmental monitoring programs have focused on organic chemicals which are known to resist degradation, bioaccumulate in the fatty tissues of organisms and have a known adverse toxicological effect. The Stockholm Convention identified several classes of chemical...

Travelers' Health: Immunocompromised Travelers

MedlinePlus

... clinical and epidemiologic studies are insufficient at this time to evaluate the actual risk of severe adverse effects associated with YF vaccine among recipients with limited immune deficits. If international travel requirements, and not true exposure risk, are the ...

Head lice. Dimeticone is the pediculicide of choice.

PubMed

2014-07-01

Infestation of the scalp by head lice, or pediculosis, is a common, unpleasant but harmless parasitosis. For patients with pediculosis, which topical treatment eradicates the parasites effectively while causing the least harm? We reviewed the available evidence using the standard Prescrire methodology. Lice can be eradicated by shaving the head or combing the hair several times a day for several weeks with a fine-toothed lice comb, although combing is only completely effective in about 50% of cases. Pyrethroids (permethrin, phenothrin and bioallethrin), often combined with piperonyl butoxide, are insecticides that are neurotoxic to lice. The lice eradication rates achieved in trials of these agents are highly variable, ranging from 13% to 75% depending on the country, probably due to the development of resistance. In five randomised trials, the organophosphorus insecticide malathion was more effective than permethrin or phenothrin, achieving eradication rates of 80% to 98%. Topical application of the insecticides ivermectin or spinosad was effective in 75% to 85% of patients in randomised trials. Insecticides have mainly local adverse effects: pruritus and irritation of the scalp. Cases of malathion poisoning have been reported following topical application or ingestion. The long-term toxicity of insecticides is unclear; it therefore appears preferable to minimise their use. Agents that kill lice through physical mechanisms have few known adverse effects. It seems unlikely that lice will develop resistance to them. Dimeticone, a silicone compound, is not absorbed through the skin and provokes very few adverse effects. It is one of the better evaluated agents: in three randomised trials, 70% to 97% of patients were lice-free after two weeks. Other agents with a physical action on lice have been evaluated, each in one randomised trial including a few dozen patients. One of these, 1,2-octanediol, applied in an alcoholic solution, seemed to eradicate lice effectively with no notable adverse effects. It is advisable to avoid aerosol formulations due to the risk of bronchospasm, products containing terpenes as these compounds can cause seizures in infants and young children, and products that lack a child-proof cap. In practice, as of early 2014, pyrethroids are no longer the first-choice treatment for head lice: they are losing effectiveness and may be toxic in the long-term. Dimeticone is a better choice, because it has few known adverse effects and proven efficacy.

Severe hypertriglyceridaemia in Type 2 diabetes mellitus: beneficial effect of continuous insulin infusion.

PubMed

Henderson, S R; Maitland, R; Mustafa, O G; Miell, J; Crook, M A; Kottegoda, S R

2013-04-01

Severe hypertriglyceridaemia is a recognized complication of Type 2 diabetes mellitus (T2DM); however, there is no consensus on acute management despite the significant risk of developing associated complications such as acute pancreatitis and hyperviscosity syndrome. To identify the association between hyperglycaemia and severe hypertriglyceridaemia in patients with T2DM and assess the effect of continuous insulin infusion therapy on serum triglyceride (TG) concentrations and report any adverse events associated with this therapeutic approach. Retrospective review of case records. Patients with uncontrolled hyperglycaemia and severe hypertriglyceridaemia (serum TG > 15 mmol/l) treated with continuous intravenous insulin infusion between October 2008 and September 2009 were retrospectively evaluated (n = 15). Details recorded included demographics, admission details, lipid profiles, glycaemic control, serum amylase and adverse events. Patients receiving treatment-dose unfractionated heparin infusion were excluded. Severe hypertriglyceridaemia is associated with hyperglycaemia in our heterogeneous group of patients with T2DM presenting with new-onset diabetes or established disease on pre-existing insulin or oral hypoglycaemic agents. Administration of continuous exogenous insulin not only achieved normoglycaemia but also dramatically corrected severe hypertriglyceridaemia in all patients (P = 0.001). The administration of continuous insulin in patients with T2DM with severe hypertriglyceridaemia is a simple and safe method of significantly reducing the immediate risk associated with this metabolic complication and should be considered in any T2DM patient presenting with severe hypertriglyceridaemia and hyperglycaemia.

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real‐world setting

PubMed Central

Seaquist, Elizabeth R.; Dulude, Hélène; Rabasa‐Lhoret, Remi; Tsoukas, George M.; Conway, James R.; Weisnagel, Stanley J.; Gerety, Gregg; Woo, Vincent C.; Zhang, Shuyu; Carballo, Dolorès; Pradhan, Sheetal; Piché, Claude A.; Guzman, Cristina B.

2018-01-01

In the present multicentre, open‐label, prospective, phase III study, we evaluated the real‐world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3‐mg dose of NG demonstrated real‐life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use. PMID:29504662

Adverse Effects of the Common Treatments for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

PubMed Central

Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J.; Sundaresh, Vishnu; Wang, Amy T.; Erwin, Patricia J.; Welt, Corrine; Ehrmann, David; Montori, Victor M.

2013-01-01

Context: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. Objective: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Data Source: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. Study Selection: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Data Extraction: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. Data Synthesis: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Conclusions: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations. PMID:24092830

Adverse effects of the common treatments for polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J; Sundaresh, Vishnu; Wang, Amy T; Erwin, Patricia J; Welt, Corrine; Ehrmann, David; Montori, Victor M; Murad, Mohammad Hassan

2013-12-01

Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

[Studies on the adverse effects of fluvoxamine treatment in children with autistic disorder: correlation with genetic polymorphism in serotonin related genes].

PubMed

Sugie, Yoko; Sugie, Hideo; Fukuda, Tokiko; Ito, Masataka; Ohzeki, Takehiko

2003-05-01

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

[Isotretinoin embryopathy: An entity that can be avoided].

PubMed

Cammarata-Scalisi, Francisco; Nieves, Dairelis; Avendaño, Andrea; Lacruz-Rengel, María A; Alviárez, Karelys; Dávila, Francys; Yavuz, Izzet; Callea, Michele

2018-04-01

Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course. Sociedad Argentina de Pediatría.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

PubMed

Gibson, P G; Reddel, H; McDonald, V M; Marks, G; Jenkins, C; Gillman, A; Upham, J; Sutherland, M; Rimmer, J; Thien, F; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Robinson, P; Wright, C; Yozghatlian, V; Burgess, S; Sivakumaran, P; Jaffe, A; Bowden, J; Wark, P A B; Yan, K Y; Kritikos, V; Peters, M; Hew, M; Aminazad, A; Bint, M; Guo, M

2016-09-01

Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting. © 2016 Royal Australasian College of Physicians.

Safety and Effectiveness of Mycophenolate in Systemic Sclerosis. A Systematic Review

PubMed Central

2015-01-01

Background Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease. Methods A literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate. Results 617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS. Conclusion Mycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement. PMID:25933090

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

PubMed

Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

Proton pump inhibitors and the risk of severe adverse events - a cardiovascular bomb?

PubMed

Cunha, Nelson; Machado, António Pedro

2018-05-24

Proton pump inhibitors are currently one of the most prescribed pharmacological classes in developed countries, given their effectiveness and safety profile previously considered favourable. However, over the last few years, several papers have been published that associate prolonged use of these drugs with a wide range of adverse effects, posing doubts about their safety. Among the adverse effects described, one should emphasize the increased risk of cardiovascular events. This relationship was first described in subjects after acute coronary syndrome by the interference of proton pump inhibitors in cytochrome P450 2C19 and the conversion of clopidogrel to active metabolite. However, more recent studies describe this relationship also with the use of antiplatelet agents that do not depend on cytochrome P450 2C19 activation. The proposed mechanism is by inhibiting dimethylarginine dimethylaminohydrolase, a physiological inhibitor of asymmetric dimethylarginine, thus increasing the plasma concentrations of the latter enzyme and in turn translating into lower levels of nitric oxide. The authors reviewing in this article the relationship between the use of proton pump inhibitors and the increased risk of cardio and cerebrovascular events, are intended to alert the scientific community to the potentially harmful effects of these drugs and recommend the setting of a moratorium on their prolonged use. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

A retrospective study on the incidences of adverse drug events and analysis of the contributing trigger factors

PubMed Central

Sam, Aaseer Thamby; Lian Jessica, Looi Li; Parasuraman, Subramani

2015-01-01

Objectives: To retrospectively determine the extent and types of adverse drug events (ADEs) from the patient cases sheets and identify the contributing factors of medication errors. To assess causality and severity using the World Health Organization (WHO) probability scale and Hartwig's scale, respectively. Methods: Hundred patient case sheets were randomly selected, modified version of the Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to identify the ADEs; causality and severity were calculated utilizing the WHO probability scale and Hartwig's severity assessment scale, respectively. Results: In total, 153 adverse events (AEs) were identified using the IHI Global Trigger Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60 adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were identified in 15 patient records. The percentage of AE/100 patients is 17%. The average ADEs/1000 doses is 2.03% (calculated). Conclusion: The IHI Global Trigger Tool is an effective method to aid provisionally-registered pharmacists to identify ADEs quicker. PMID:25767366

Application of ToxCast to evaluate potential biological effects from organic contaminants in Great Lakes tributaries

EPA Science Inventory

With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemica...

EVALUATION OF COARSE, FINE, AND ULTRAFINE PARTICLES AS PART OF A HEALTH EFFECTS EXPOSURE STUDY

EPA Science Inventory

Ambient PM is a complex mixture that includes bioactive and toxic compounds of natural and anthropogenic origin, several of which have been theorized to be causative or contributory to the adverse effects of PM inhalation. Numerous epidemiological studies have reported associ...

Recent Updates on the Systemic and Local Safety of Intranasal Steroids.

PubMed

Jang, Tae Young; Kim, Young Hyo

2016-01-01

Allergic rhinitis is a global health problem, and its prevalence rate and socioeconomic burden continue to increase. Intranasal steroid (INS) is the first treatment choice in the majority of patients, because of its ability to effectively control allergic symptoms. However, patients and clinicians are concerned about the potential adverse effects of prolonged INS use. We performed to review for evaluating systemic and local safety of INS use, by searching MEDLINE, EMBASE, and Cochrane Library database for identification of relevant articles. In the present study, the systemic bioavailabilities of several commercially available INSs were researched, and then systemic safeties were reviewed with focus on suppression of the hypothalamus-pituitary-adrenal axis and their effects on pediatric growth. In addition, local adverse effects, such as, epistaxis and nasal septal perforation, were investigated. Finally, the authors proposed some techniques in order to avoid these complications. INSs offer a safe, effective means of treating allergic rhinitis in the short- and long-term with no or minimal adverse systemic and local effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Detailed Assessments of Childhood AdversityEnhance Prediction of Central Obesity Independent of Gender, Race, Adult Psychosocial Risk and Health Behaviors

PubMed Central

Davis, Cynthia R.; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T.; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S.; Crowell, Judith A.

2017-01-01

Objective This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of “modifiable” risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities X severity X chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. Materials/Methods 210 Black/African Americans and White/European Americans, mean age = 45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Results Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Conclusions Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. PMID:24211017

Early Socioeconomic Adversity and Young Adult Physical Illness: The Role of Body Mass Index and Depressive Symptoms

PubMed Central

Wickrama, K. A. S.; Kwon, Josephine A.; Oshri, Assaf; Lee, Tae Kyoung

2014-01-01

Purpose The present study investigated the psycho-physiological inter and intra-individual processes that mediate the linkage between childhood/adolescent socioeconomic adversities and adult health outcomes. Specifically, the proposed model examined the roles of youth depressive symptoms and BMI trajectories as mediators that explain the link between early adversity and young adults’ general health and physical illnesses after controlling for gender, race/ethnicity, and earlier general health reports. Methods Using a nationally representative sample of 12,424 from National Longitudinal Study of Adolescent Health (Add Health), this study used growth curve modeling to consider both the severity (initial level) as well as the change over time (deterioration or elevation) as psycho-physiological mediators, thereby acknowledging multiple facets of depressive symptoms and BMI trajectories as psych-physiological mediators of early adversity to adult health. Results Results provide evidence for (a) the influence of early childhood and early adolescent cumulative socioeconomic adversity on both the initial levels and changes over time of depressive symptoms and BMI and (b) the independent influences depressive symptoms and BMI trajectories on the general health and the physical illnesses of young adults Conclusions These findings contribute valuable knowledge to existing research by elucidating how early adversity exerts an enduring long-term influence on physical health problems in young adulthood; further, this information suggests effective intervention and prevention programs should incorporate multiple facets (severity and change over time) of multiple mechanisms (psychological and physiological). PMID:24856408

The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.

PubMed

Tan, Yafei; Yang, Rong; Zhao, Jinzhu; Cao, Zhongqiang; Chen, Yawen; Zhang, Bin

2017-01-01

Research on the potential impact of air pollution on the human's health has increased rapidly in recent years. Several studies have suggested that exposure to air pollutants during period of pregnancy which is a crucial time point of mother-fetus development may have long-term and serious impact on adverse pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic evidence on the associations between air pollutants and adverse pregnancy outcomes in China, so we conducted a review to explore the current epidemiological evidence on the effects of air pollutants to pregnancy outcomes and possible mechanisms during the pregnancy process. We used keywords to systematically search all the English and Chinese literatures on studies that were conducted in China. Exposure to air pollutants during pregnancy had shown there were harmful effects for different birth outcomes: preterm birth, low birth weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on the effects of air pollutants on adverse pregnancy outcomes are small and inconsistent because they vary in their design and methodology. The existed available evidence is compatible with either a small negative effect of air pollutants on pregnancy outcomes or with no effect; therefore, further studies are needed to confirm and quantify the possible associations and potential biologic mechanisms between air pollutants and pregnancy outcomes.

Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study

PubMed Central

Trotta, Antonella; Iyegbe, Conrad; Di Forti, Marta; Sham, Pak C.; Campbell, Desmond D.; Cherny, Stacey S.; Mondelli, Valeria; Aitchison, Katherine J.; Murray, Robin M.

2016-01-01

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis. PMID:27648571

Preadoption adversity, MAOA, and behavioral adjustment in internationally adopted Chinese girls.

PubMed

Li, Jun; Tan, Tony Xing; Camras, Linda A; Chen, Chuansheng; Moyzis, Robert K

2014-10-01

We studied postinstitutionalized adopted Chinese girls to determine whether those with different variants of the MAOA gene promoter region (MAOA-VNTR) differed in their internalizing and externalizing behavior problems and whether the MAOA genotype moderated the relation between preadoption adversity and current behavior problems. MAOA genotyping was obtained for 94 girls (mean age: 9.2 years) and the number of 4-repeat (4R) alleles was determined (zero, one, or two). The adoptive mothers rated several indicators of preadoption adversity shortly after adoption (mean age at adoption 15.8 months) and completed the Child Behavior Checklist when the children were 8.1 years on average. No main effects were found for preadoption adversity. However, the MAOA genotype had a nominally significant effect (P<0.05) on internalizing problems. Regression analyses controlling for age, household income, authoritarian parenting, and family problems showed that among children with no physical signs of preadoption adversity, those carrying a greater number of 4R alleles scored significantly lower (P<0.01) on internalizing problems than those with fewer 4R alleles. Differences in internalizing scores related to the MAOA genotype were not observed for children who showed one or more physical signs of adversity at the time of adoption. A similar pattern was found for externalizing problems, although the results did not reach conventional levels of significance. Our results suggest that higher MAOA activity may be protective with respect to internalizing problems in internationally adopted Chinese girls, but that this protective effect decreases at higher levels of preadoption adversity. A similar pattern may exist for externalizing problems.

Oral adverse effects due to the use of Nevirapine.

PubMed

Moura, Mariela Dutra Gontijo; Senna, Maria Inês Barreiros; Madureira, Davidson Fróis; Fonseca, Linaena Merícy Silva; Mesquita, Ricardo Alves

2008-01-01

The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.

Dietary fats and health: dietary recommendations in the context of scientific evidence.

PubMed

Lawrence, Glen D

2013-05-01

Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.

A rare case of imatinib-induced erythroderma

PubMed Central

Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran; Neema, Shekhar

2013-01-01

Imatinib, a specific tyrosine kinase inhibitor is a newer anticancer agent, which has shown excellent efficacy in managing chronic myeloid leukemia. It is generally well tolerated with few side effects. Most commonly reported adverse events are maculopapular eruptions and periorbital edema. Severe adverse reactions are seen in 5% of patients. Exfoliative dermatitis has been very rarely reported with this drug. We report a case of a 52-year-old male who initially presented with a maculopapular rash and developed erythroderma on continuation of the drug. PMID:24347779

Novel Opioid Analgesics and Side Effects.

PubMed

Del Vecchio, Giovanna; Spahn, Viola; Stein, Christoph

2017-08-16

Conventional opioids mediate analgesia as well as severe adverse effects via G-protein coupled opioid receptors (OR) in both inflamed (peripheral injured tissue) and healthy (brain, intestinal wall) environments. To exclude side effects, OR activation can be selectively achieved in damaged tissue by lowering the pK a of an opioid ligand to the acidic pH of inflammation. As a result, protonation of the ligand and consequent OR binding and activation of G-proteins is pH- and injury-specific. A novel compound (NFEPP) demonstrates the feasibility of this approach and displays blockade of pain transmission only at the peripheral site of injury, but with lack of central and gastrointestinal adverse effects. These findings suggest disease-specific receptor activation as a new strategy in drug design.

78 FR 41059 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... for biodiesel, water/diesel emulsions, several atypical additives, and renewable gasoline and diesel... adverse health effects. Tier 2 data have been submitted for baseline diesel, biodiesel, and water/diesel...

Ipilimumab associated colitis: an IpiColitis case series at MedStar Georgetown University Hospital.

PubMed

Rastogi, Pawan; Sultan, Mohamed; Charabaty, Aline J; Atkins, Michael B; Mattar, Mark C

2015-04-14

Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern. The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects. One of the most concerning effects is the development of colitis. Upwards to 8% of patients have been reported to develop colitis, with 5% being severe (Grades 3-4). While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids. Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids. We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.

Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

PubMed

Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

2015-05-21

Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

PubMed

Gutiérrez Fernández, D; Moreno-Ancillo, A; Fernández Meléndez, S; Domínguez-Noche, C; Gálvez Ruiz, P; Alfaya Arias, T; Carballada González, F; Alonso Llamazares, A; Marques Amat, L; Vega Castro, A; Antolín Amérigo, D; Cruz Granados, S; Ruiz León, B; Sánchez Morillas, L; Fernández Sánchez, J; Soriano Gomis, V; Borja Segade, J; Dalmau Duch, G; Guspi Bori, R; Miranda Páez, A

2016-01-01

Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data.

PubMed

Cools, Filip; Askie, Lisa M; Offringa, Martin; Asselin, Jeanette M; Calvert, Sandra A; Courtney, Sherry E; Dani, Carlo; Durand, David J; Gerstmann, Dale R; Henderson-Smart, David J; Marlow, Neil; Peacock, Janet L; Pillow, J Jane; Soll, Roger F; Thome, Ulrich H; Truffert, Patrick; Schreiber, Michael D; Van Reempts, Patrick; Vendettuoli, Valentina; Vento, Giovanni

2010-06-12

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. Nestlé Belgium, Belgian Red Cross, and Dräger International.

Update on Psychological Trauma, Other Severe Adverse Experiences and Eating Disorders: State of the Research and Future Research Directions.

PubMed

Trottier, Kathryn; MacDonald, Danielle E

2017-08-01

This paper provides an updated review of the literature on the relationship between psychological trauma exposure, other severe adverse experiences, and eating disorders. Trauma exposure and other severe adverse experiences (e.g., emotional abuse) in both childhood and adulthood are associated with eating disorders. The relationship between traumatic and other adverse experiences and eating disorders appears to be mediated by emotional and behavioral dysregulation, as well as by cognitive factors such as self-criticism. Biological vulnerabilities may also be relevant to this relationship. Overall, the literature is limited by predominantly cross-sectional designs. There is clear evidence of a correlational relationship between trauma exposure and other severe adverse events, and eating disorders. Both risk and maintenance factor hypotheses have been put forth; however, prospective research testing these hypotheses remains limited. Future research should use prospective designs and focus on trauma-related symptoms (rather than trauma exposure) in order to advance research on risk and maintaining factors for eating disorders and inform treatment directions.

Public health implications of smokeless tobacco use as a harm reduction strategy.

PubMed

Savitz, David A; Meyer, Roger E; Tanzer, Jason M; Mirvish, Sidney S; Lewin, Freddi

2006-11-01

Harm reduction strategies involve promoting a product that has adverse health consequences as a substitute for one that has more severe adverse health consequences. Smokeless tobacco low in nitrosamine content offers potential benefits in reducing smoking prevalence rates. Possible harm arises from the potential for such products to serve as a gateway to more harmful tobacco products, public misinterpretation of "less harmful" as "safe," distraction from the public health goal of tobacco elimination, and ethical issues involved in advising those marketing these harmful products. We offer a research agenda to provide a stronger basis for evaluating the risks and benefits of smokeless tobacco as a means of reducing the adverse health effects of tobacco.

Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

PubMed

Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine; Fink-Jensen, Anders; Nielsen, Jimmi

2016-10-01

Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients.

Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects.

PubMed

Pagano, Giovanni; Guida, Marco; Tommasi, Franca; Oral, Rahime

2015-05-01

In the recent decades, rare earth elements (REE) have undergone a steady spread in several industrial and medical applications, and in agriculture. Relatively scarce information has been acquired to date on REE-associated biological effects, from studies of bioaccumulation and of bioassays on animal, plant and models; a few case reports have focused on human health effects following occupational REE exposures, in the present lack of epidemiological studies of occupationally exposed groups. The literature is mostly confined to reports on few REE, namely cerium and lanthanum, whereas substantial information gaps persist on the health effects of other REE. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, analogous to the recognized redox mechanisms observed for other transition elements. Adverse outcomes of REE exposures include a number of endpoints, such as growth inhibition, cytogenetic effects, and organ-specific toxicity. An apparent controversy regarding REE-associated health effects relates to opposed data pointing to either favorable or adverse effects of REE exposures. Several studies have demonstrated that REE, like a number of other xenobiotics, follow hormetic concentration-related trends, implying stimulatory or protective effects at low levels, then adverse effects at higher concentrations. Another major role for REE-associated effects should be focused on pH-dependent REE speciation and hence toxicity. Few reports have demonstrated that environmental acidification enhances REE toxicity; these data may assume particular relevance in REE-polluted acidic soils and in REE mining areas characterized by concomitant REE and acid pollution. The likely environmental threats arising from REE exposures deserve a new line of research efforts. Copyright © 2015 Elsevier Inc. All rights reserved.

Predicting Long-Term Outcomes for Women Physically Abused in Childhood: Contribution of Abuse Severity versus Family Environment

ERIC Educational Resources Information Center

Griffin, Margaret L.; Amodeo, Maryann

2010-01-01

Objective: Child physical abuse (CPA) has been associated with adverse adult psychosocial outcomes, although some reports describe minimal long-term effects. The search for the explanation for heterogeneous outcomes in women with CPA has led to an examination of a range of CPA-related factors, from the severity of CPA incidents to the childhood…

Predicting Long-Term Outcomes for Women Sexually Abused in Childhood: Contribution of Abuse Severity Versus Family Environment

ERIC Educational Resources Information Center

Fassler, I.R.; Amodeo, M.; Griffin, M.L.; Clay, C.M.; Ellis, M.A.

2005-01-01

Objective:: Child sexual abuse (CSA) has been associated with adverse adult psychosocial outcomes, although some reports describe minimal long-term effects. The search for explanations for the heterogeneous outcomes in women with CSA has led to an examination of a range of CSA-related factors, from the severity of individual CSA incidents to the…

Impact of Posttraumatic Stress Disorder and Injury Severity on Recovery in Children with Traumatic Brain Injury

ERIC Educational Resources Information Center

Kenardy, Justin; Le Brocque, Robyne; Hendrikz, Joan; Iselin, Greg; Anderson, Vicki; McKinlay, Lynne

2012-01-01

The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a…

Efficacy of butylscopolamine for the treatment of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.

PubMed

Ryu, J H; Hwang, J W; Lee, J W; Seo, J H; Park, H P; Oh, A Y; Jeon, Y T; Do, S H

2013-12-01

Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries. Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug. The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups. Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.

The association of chronic adversity with psychiatric disorder and disorder severity in adolescents.

PubMed

Benjet, Corina; Borges, Guilherme; Méndez, Enrique; Fleiz, Clara; Medina-Mora, Maria Elena

2011-09-01

The purpose of this paper is to estimate the impact of chronic adversity on psychopathology in adolescents, taking into account the type of adversity, number of adversities experienced and type of psychiatric disorder, as well as to estimate the impact on severity of the disorder. A total of 3,005 male and female adolescents from the Mexican Adolescent Mental Health Survey aged 12-17 years were interviewed in a stratified multistage general population probability survey. Assessment of 20 DSM-IV disorders, disorder severity and 12 chronic childhood adversities were assessed with the adolescent version of the World Mental Health Composite International Diagnostic Interview (WMH-CIDI-A). Family dysfunction adversities including abuse presented the most consistent associations between chronic adversity and psychopathology and their impact was generally non-specific with regard to the type of disorder. Parental divorce, parental death and economic adversity were not individually associated with psychopathology. Among those with a psychiatric disorder, sexual abuse and family violence were associated with having a seriously impairing disorder. The odds of having a psychiatric disorder and a serious disorder increased with increasing numbers of adversities; however, each additional adversity increased the odds at a decreasing rate. While the study design does not allow for conclusions regarding causality, these findings suggest general pathways from family dysfunction to psychopathology rather than specific associations between particular adversities and particular disorders, and provide further evidence for the importance of family-focused intervention and prevention efforts.

A Randomized Comparative Trial on the Therapeutic Efficacy of Topical Aloe vera and Calendula officinalis on Diaper Dermatitis in Children

PubMed Central

Panahi, Yunes; Sharif, Mohamad Reza; Sharif, Alireza; Beiraghdar, Fatemeh; Zahiri, Zahra; Amirchoopani, Golnoush; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

2012-01-01

Introduction. Diaper dermatitis (DD) is a common inflammatory disorder among children and infants. The objective of the present randomized and double-blind trial was to compare the therapeutic efficacies of Aloe vera cream and Calendula officinalis ointment on the frequency and severity of DD in children. Methods. Sixty-six infants with DD (aged < 3 years) were randomized to receive either Aloe cream (n = 32) or Calendula ointment (n = 34). Infants were treated with these drugs 3 times a day for 10 days. The severity of dermatitis was graded at baseline as well as at the end of trial using a 5-point scale. The adverse effects of study medications were assessed during the trial. Results. Although improvement in the severity of DD was observed in both treatment groups (P < 0.001), patients receiving Calendula ointment had significantly fewer rash sites compared to Aloe group (P = 0.001). No adverse effect was reported from either of the medications. Discussion. The evidence from this study suggests that topical Aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants. PMID:22606064

A randomized comparative trial on the therapeutic efficacy of topical aloe vera and Calendula officinalis on diaper dermatitis in children.

PubMed

Panahi, Yunes; Sharif, Mohamad Reza; Sharif, Alireza; Beiraghdar, Fatemeh; Zahiri, Zahra; Amirchoopani, Golnoush; Marzony, Eisa Tahmasbpour; Sahebkar, Amirhossein

2012-01-01

Diaper dermatitis (DD) is a common inflammatory disorder among children and infants. The objective of the present randomized and double-blind trial was to compare the therapeutic efficacies of aloe vera cream and Calendula officinalis ointment on the frequency and severity of DD in children. Sixty-six infants with DD (aged < 3 years) were randomized to receive either aloe cream (n = 32) or Calendula ointment (n = 34). Infants were treated with these drugs 3 times a day for 10 days. The severity of dermatitis was graded at baseline as well as at the end of trial using a 5-point scale. The adverse effects of study medications were assessed during the trial. Although improvement in the severity of DD was observed in both treatment groups (P < 0.001), patients receiving Calendula ointment had significantly fewer rash sites compared to aloe group (P = 0.001). No adverse effect was reported from either of the medications. The evidence from this study suggests that topical aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Bisphenol A and human health: a review of the literature.

PubMed

Rochester, Johanna R

2013-12-01

There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Countermeasures for space radiation induced adverse biologic effects

NASA Astrophysics Data System (ADS)

Kennedy, A. R.; Wan, X. S.

2011-11-01

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

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

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

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

2016-03-15

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

Methylation of Exons 1D, 1F, and 1H of the Glucocorticoid Receptor Gene Promoter and Exposure to Adversity in Pre-School Aged Children

PubMed Central

Tyrka, Audrey R.; Parade, Stephanie H.; Eslinger, Nicole M.; Marsit, Carmen J.; Lesseur, Corina; Armstrong, David A.; Philip, Noah S.; Josefson, Brittney; Seifer, Ronald

2016-01-01

Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR) which is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n=74 with child welfare documentation of moderate-severe maltreatment in the past six months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of NR3C1. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the bio-behavioral effects of adverse exposures in young children. PMID:25997773

Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non-small cell lung cancer: a meta-analysis

PubMed Central

Hu, Yang-Bo; Zhang, Qun; Li, Hui-Juan; Michot, Jean Maire; Liu, Hong-Bing

2017-01-01

Background Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy. Methods PubMed was searched up to 24 March 2017 for clinical trials of PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) in treatment of NSCLC. Besides, references of relevant articles were screened. Results Finally, 22 trials were included in our study, 14 with data of pneumonitis, 19 with other severe IRAEs or treatment related deaths and 5 with control groups. Incidence of all-grade pneumonitis was 2.9% (95% CI, 2.0–4.8%) and grade 3 or higher pneumonitis 2.0% (95% CI, 1.0–2.0%). Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32–4.20, P=0.004), but had no significance in grade 3–5 pneumonitis. Incidence of cardiorespiratory arrest (n=537) was 1.0% (95% CI, 0–2.0%), cardiac failure (n=214) 2.0% (95% CI, 1.0–5.7%), myocardial infarction (n=402) 1.0% (95% CI, 0–3.8%), stroke (n=135) 2.0% (95% CI, 0–13.0%), disease progression (n=391) 1.0% (95% CI, 0–2.9%), pancreatitis (n=700) 1.0% (95% CI, 0–2.0%) and severe skin reactions (n=836) 2.0% (95% CI, 1.0–3.8%). Incidence of treatment related deaths was 0.7%. Conclusions Immune related adverse effects can on occasion be life-threatening even though usually rare. Incidence of pneumonitis in PD-1 and PD-L1 inhibitors was significantly higher than that in chemotherapy. More studies should be conducted to investigate the incidence of these rare but life-threatening IRAEs. PMID:29299404

Off-label use of TNF-alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients.

PubMed

Sand, Freja Lærke; Thomsen, Simon Francis

2015-01-01

Tumor necrosis factor-alpha (TNF)-alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF-alpha inhibitors have also been used off-label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF-alpha inhibitors used for off-label dermatological indications. We retrospectively evaluated patient records of 118 patients treated off-label with TNF-alpha inhibitors in a dermatological university department. Patients presented with severe aphthous stomatitis/genital aphthous lesions (26), chronic urticaria (25), hidradenitis suppurativa (29), acne conglobata (11), dissecting cellulitis of the scalp (two), orofacial granulomatosis (four), sarcoidosis (four), granuloma annulare (two), granulomatous rosacea (one), granuloma faciale (one), subcorneal pustulosis (one), pyoderma gangrenosum (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse effects during therapy. Off-label therapy with TNF-alpha inhibitors may be considered for selected patients with severe recalcitrant mucocutaneous diseases. The risk of severe adverse effects signals that a thorough benefit-risk assessment should be performed before initiating off-label treatment with TNF-alpha inhibitors for these conditions. © 2015 Wiley Periodicals, Inc.

Pharmacology of the Phosphate Binder, Lanthanum Carbonate

PubMed Central

Damment, Stephen JP

2011-01-01

Studies were conducted to compare the phosphate-binding efficacy of lanthanum carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received lanthanum carbonate, aluminum hydroxide, calcium carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum carbonate and aluminum hydroxide markedly increased excretion of [32P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, lanthanum carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of lanthanum carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that lanthanum carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses. PMID:21332344

Association of PCBs and allergies in children.

PubMed

Tsuji, Mayumi; Kawamoto, Toshihiro; Koriyama, Chihaya; Yamamoto, Megumi; Tsuchiya, Takuto; Matsumura, Fumio

2015-05-01

Recently, the incidence rates of childhood allergies have been rising around the world. The presence of persistent chemical pollutants in the environment and exposure to air pollutants are often cited as potential causes of childhood allergies. Accordingly, epidemiological studies of the associations between exposure to low levels of pollutants and adverse health effects are essential. However, at present no useful biomarkers for evaluating such associations have been developed. Thus, using a molecular epidemiological approach we planned to identify candidate biomarkers of pollutant-induced adverse health effects that can be used in children. In asthmatic children, we found that the serum levels of several polychlorinated biphenyl (PCB) congener sub-types were significantly positively correlated with interleukin (IL)-8 mRNA expression, whereas in a sub-group of children who displayed positive immunoglobulin E (IgE) responses to milk or egg proteins IL-22 mRNA expression was demonstrated to be useful for detecting the adverse health effects of environmental pollutants, particularly PCB congeners. In conclusion, the mRNA expression levels of IL-8 and IL-22 can be used to detect children who are at particular risk of adverse health events caused by environmental pollutants, especially PCBs. Copyright © 2014 Elsevier Inc. All rights reserved.

Family Social Support Modifies the Relationships between Childhood Maltreatment Severity, Economic Adversity and Postpartum Depressive Symptoms

PubMed Central

Umarji, Rujuta; Sexton, Minden B.; Davis, Margaret T.

2016-01-01

Objectives This study examines the main and moderating effects of childhood abuse or neglect severity, income, and family social support on the presence of postpartum depressive symptoms (PDS). Methods Participants included 183 postpartum mothers who endorsed a history of childhood maltreatment (CM) and enrolled in a longitudinal study of mother and child outcomes. Participants completed questionnaires to assess CM severity, associated societal and maternal characteristics, and depressive symptom severity. Results The results confirm previously identified links between CM severity and PDS. Further, hierarchical linear regression analyses indicate the interaction of household income and interpersonal support from the family attenuates the relationship between CM severity and PDS. The final model accounted for 29% of the variance of PDS scores, a large effect size. Conclusions This study is the first to demonstrate interrelationships between income and social support on resilience to postpartum psychopathology in childhood trauma-surviving women. Social support appeared to protect against PDS for all mothers in this study while income only conferred a protective effect when accompanied by family support. For clinicians, this implies the need to focus on improving family and other relationships, especially for at-risk mothers. Significance A history of CM has demonstrated deleterious effects in general and postpartum populations. Given the potential negative impact on mothers and their children, investigators have examined the potential for income and social support to protect against adverse outcomes. Our study adds to this literature by examining the variance explained by CM severity and the interaction of family support and income on depression following childbirth. Our unique findings identify specific contexts in which family support and income buffer against CM-PDS associations for women with compound risks. As such, particular policies and clinical interventions may be more strategically tailored for this population. PMID:28028663

Late-onset immune-mediated adverse effects after poly-L-lactic acid injection in non-HIV patients: clinical findings and long-term follow-up.

PubMed

Alijotas-Reig, Jaume; Garcia-Gimenez, Victor; Vilardell-Tarres, Miquel

2009-01-01

It has been thought that poly-L-lactic acid (PLLA) injections do not have inflammatory side effects. Recent evidence shows that local/regional/systemic delayed adverse effects may appear with its use. To evaluate the clinical complaints, treatment response and long-term follow-up of non-HIV patients with delayed immune-mediated adverse effects related to PLLA injections. Prospective, case series study of 10 patients with delayed adverse effects related to PLLA injections. The inclusion criterion was defined as the onset at least 6 months after PLLA use, with 1 or more of the following clinical signs: oedema, skin induration, swelling/tender nodules with or without discharge of pus or filler material. Several systemic manifestations were also included. Patients with immediate side effects were excluded. Patients underwent clinical management and long-term follow-up. The average latency period to the onset of symptoms was 19.2 months (range: 6-60). Tender, inflammatory nodules and facial oedema were commonly seen. One case presented a systemic granulomatous disorder as a complication. After 50.2 months of average follow-up (range: 38-78), 5 patients are in remission, 4 have recurrent bouts and the last case has been lost to follow-up. Although infrequently, local and/or regional and/or systemic delayed and recurrent granulomatous reactions may complicate PLLA gel injections. Copyright 2009 S. Karger AG, Basel.

Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

PubMed

Singh, Abhishank; Dwivedi, Shridhar

2017-02-01

The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

Bradycardia and Hypothermia Complicating Azithromycin Treatment.

PubMed

Benn, Kerri; Salman, Sam; Page-Sharp, Madhu; Davis, Timothy M E; Buttery, Jim P

2017-08-11

BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35.2°C) and bradycardia (65 beats/minute) after the second dose, which resolved over several days post-treatment, consistent with persistence of high tissue azithromycin concentrations relative to those in plasma. A sigmoid Emax pharmacokinetic/pharmacodynamic model suggested a maximal azithromycin-associated reduction in heart rate of 23 beats/minute. Monitoring for these potential adverse effects should facilitate appropriate supportive care in similar cases. CONCLUSIONS Recommended azithromycin doses can cause at least moderate bradycardia and hypothermia in vulnerable pediatric patients, adverse effects that should prompt appropriate monitoring and which may take many days to resolve.

Economics and societal considerations of drought

Treesearch

Jeff Prestemon; Linda Kruger; Karen L. Abt; Michael Bowker; Consuelo Brandeis; Dave Calkin; Geoffrey H. Donovan; Charlotte Ham; Thomas P. Holmes; Jeffrey Kline; Travis Warziniack

2016-01-01

The economic and social effects of drought are diverse and related to physical characteristics of drought, including spatial extent, severity, duration, and frequency that combine to determine drought’s overall effects on society. Most of the attention given to economic and social impacts of drought focuses on adverse consequences, but technology, public...

Prospective Evaluation of Severe Skin Toxicity and Pain During Postmastectomy Radiation Therapy

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

Pignol, Jean-Philippe, E-mail: j.p.pignol@erasmusmc.nl; Vu, Thi Trinh Thuc; Mitera, Gunita

Purpose: To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects. Methods and Materials: Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain. Results: Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grademore » 3 moist desquamation was significantly associated with severe pain (P<.001). On multivariate analysis, smoking, high-energy photons, and skin bolus were significantly associated with severe moist desquamation. Skin toxicity doubled for smokers, with 40% severe pain, 48% grade 3 moist desquamation, and 64% grade 3 skin toxicity. Without skin bolus 4.2% had severe pain, none moist desquamation, and 2.1% grade 3 skin toxicity. When skin bolus was used on alternate days, the frequency increased to 15% for pain, 22% for moist desquamation, and 26% for grade 3 skin toxicity. When bolus was used daily, 32% had pain, 41% moist desquamation, and 47% grade 3 skin toxicity. Symptoms peaked 1 to 2 weeks after the end of PMRT. Conclusions: The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus.« less

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Symptoms of Common Mental Disorders and Adverse Health Behaviours in Male Professional Soccer Players

PubMed Central

Gouttebarge, Vincent; Aoki, Haruhito; Kerkhoffs, Gino

2015-01-01

To present time, scientific knowledge about symptoms of common mental disorders and adverse health behaviours among professional soccer players is lacking. Consequently, the aim of the study was to determine the prevalence of symptoms of common mental disorders (distress, anxiety/depression, sleep disturbance) and adverse health behaviours (adverse alcohol behaviour, smoking, adverse nutrition behaviour) among professional soccer players, and to explore their associations with potential stressors (severe injury, surgery, life events and career dissatisfaction). Cross-sectional analyses were conducted on baseline questionnaires from an ongoing prospective cohort study among male professional players. Using validated questionnaires to assess symptoms of common mental disorders and adverse health behaviours as well as stressors, an electronic questionnaire was set up and distributed by players’ unions in 11 countries from three continents. Prevalence of symptoms of common mental disorders and adverse health behaviours among professional soccer players ranged from 4% for smoking and 9% for adverse alcohol behaviour to 38% for anxiety/depression and 58% for adverse nutrition behaviour. Significant associations were found for a higher number of severe injuries with distress, anxiety/depression, sleeping disturbance and adverse alcohol behaviour, an increased number of life events with distress, sleeping disturbance, adverse alcohol behaviour and smoking, as well as an elevated level of career dissatisfaction with distress, anxiety/depression and adverse nutrition behaviour. Statistically significant correlations (p<0.01) were found for severe injuries and career dissatisfaction with most symptoms of common mental disorders. High prevalence of symptoms of common mental disorders and adverse health behaviours was found among professional players, confirming a previous pilot-study in a similar study population. PMID:26925182

Review on intrauterine programming: Consequences in rodent models of mild diabetes and mild fat overfeeding are not mild.

PubMed

Jawerbaum, A; White, V

2017-04-01

An adverse intrauterine programming occurs in diabetes and obesity as the consequence of an adverse maternal environment that affects the appropriate fetoplacental development and growth. Experimental models of diabetes and fat overfeeding have provided relevant tools to address putative mechanisms of the adverse intrauterine programming. The current knowledge far extends from the original thoughts of the resulting intrauterine programming of metabolic and cardiovascular diseases to a full range of alterations that affect multiple tissues, organs, and systems that will compromise the long-life health of the offspring. This review examines the postnatal effects of rodent models of mild diabetes and fat overfeeding, identifying the multiple organ derangements in the offspring resulting from mild maternal adverse conditions. In addition, the comparison of experimental models of severe diabetes and fat overfeeding and the crucial role of the placenta are discussed, providing an update of the actual scenario of the putative mechanisms and adverse consequences of maternal metabolic derangements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Otorhinolaryngological Toxicities of New Drugs in Oncology.

PubMed

Hartl, Dana M; Morel, Daphné; Saavedra, Erika; Massard, Christophe; Rinaldo, Alessandra; Saba, Nabil F; Ferlito, Alfio; Soria, Jean-Charles

2017-04-01

Many new or relatively new cancer drugs-personalized anticancer agents-have been approved for use in various clinical settings in oncology or are still under evaluation in clinical trials. Targeted therapies as well as new immune checkpoint blockers have toxicity profiles that differ from conventional cytotoxic chemotherapy, and many can cause adverse effects that affect the mouth and pharynx, the nasal cavities, and the larynx. This review aims to provide an overview of current knowledge concerning these side effects and contemporary management. Adverse effects of the mouth/pharynx, nasal cavities, larynx, and cochlear-vestibular system are generally low grade (according to the Common Terminology Criteria for Adverse Events) and generally present non-life-threatening symptoms. However, the impact on patients' quality of life could be important. The incidence and severity vary according to the drug, its target(s), and dose, but there are currently no known predictive factors, and each patient has an individual toxicity profile. Management guidelines are based on expert opinion. These ear, nose, and throat adverse effects are not frequently mentioned in the literature because of the often non-specific nature of the symptoms and their mildness, but also the absence of specific treatment. These symptoms can contribute to decreased quality of life and lead to drug compliance issues if not diagnosed and managed appropriately.

Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy.

PubMed

Eigentler, Thomas K; Hassel, Jessica C; Berking, Carola; Aberle, Jens; Bachmann, Oliver; Grünwald, Viktor; Kähler, Katharina C; Loquai, Carmen; Reinmuth, Niels; Steins, Martin; Zimmer, Lisa; Sendl, Anna; Gutzmer, Ralf

2016-04-01

PD-1 checkpoint inhibitors are associated with a specific spectrum of immune-related adverse events. This spectrum is different from toxicities known for kinase inhibitors or cytotoxic drugs. Since PD-1 directed therapies show effectivity in an increasing number of malignant diseases, their clinical usage will increase rapidly. Therefore clinicians from different specialities such as medical oncology, internal medicine, family doctors and emergency unit staff should be aware of the adverse effects of PD-1 checkpoint inhibitors to avoid delays in diagnosis and treatment. Based on pooled data from pivotal trials as reported by the European Medicines Agency, the present paper reviews incidences and kinetics of onset and resolution of immune-mediated "adverse events of specific interest" (AEOSI) of both approved PD-1 inhibitors nivolumab and pembrolizumab. In general, the severity of AEOSI is mild to moderate (grade 1-2); the frequency of immune-mediated but also idiopathic grade 3-4 adverse drug reactions is ⩽2% for any event term. Recommendations for the diagnosis, monitoring and management of the relevant dermatological, gastrointestinal, pulmonary, endocrine, renal and hepatic toxicities are convened by an expert panel that consolidated and clarified treatment recommendations after the onset of AEOSI. Although the time of onset is not predictable - the medians range from 1 to 6months - the huge majority of events is reversible, with no impact of the time of onset. By the systemic use of glucocorticoids, notably methylprednisolone or equivalents, most AEOSI are well manageable. Non-steroidal immunosuppressants may be used in certain cases of refractory/recalcitrant, long-lasting immune toxicities. With regard to the outstanding clinical activity of the anti-PD-1 antibodies, therapy restart is the principal therapeutic option after recovery of grade 2 AEOSI, or diminution of higher grade skin or endocrine events to mild severity. Early diagnosis and close clinical monitoring are essential for successful management of immune-related adverse events. Copyright © 2016 Elsevier Ltd. All rights reserved.

Growing up with adversity: From juvenile justice involvement to criminal persistence and psychosocial problems in young adulthood.

PubMed

Basto-Pereira, Miguel; Miranda, Ana; Ribeiro, Sofia; Maia, Ângela

2016-12-01

Several studies have been carried out to investigate the effect of child maltreatment on juvenile justice involvement and future criminal life. However, little is known about the impact of other forms of adversity, beyond abuse and neglect, on juvenile delinquency and criminal persistence. The effect of early adversity on psychosocial problems is underexplored, particularly in juvenile delinquents. This study, using the Childhood Adverse Experiences (ACE) questionnaire, a tool accessing the exposure to different types of abuse, neglect and serious household dysfunction, explored the role of each adverse experience on juvenile justice involvement, persistence in crime and psychosocial problems during young adulthood. A Portuguese sample of 75 young adults with official records of juvenile delinquency in 2010/2011, and 240 young adults from a community sample completed ACE questionnaire and measures of psychosocial adjustment. Seven out of ten adverse experiences were significantly more prevalent in young adults with juvenile justice involvement than in the community sample, after matching the main demographic variables. The strongest predictor of juvenile justice involvement and criminal persistence during early adulthood was sexual abuse. Dimensions of child/adolescent emotional maltreatment and a mental illness in the household predicted a set of psychosocial problems in young adulthood. This study indicates that early adversity is significantly related to juvenile justice involvement, criminal persistence and psychosocial problems. This study also suggests that each experience has a different role in this process. There is an urgent need to screen, prevent and stop serious adversity. Future scientific directions and recommendations for policies are provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Delayed surgery after acute traumatic central cord syndrome is associated with reduced mortality.

PubMed

Samuel, Andre M; Grant, Ryan A; Bohl, Daniel D; Basques, Bryce A; Webb, Matthew L; Lukasiewicz, Adam M; Diaz-Collado, Pablo J; Grauer, Jonathan N

2015-03-01

A retrospective study of surgically treated patients with acute traumatic central cord syndrome (ATCCS) from the National Trauma Data Bank Research Data Set. To determine the association of time to surgery, pre-existing comorbidities, and injury severity on mortality and adverse events in surgically treated patients with ATCCS. Although earlier surgery has been shown to be beneficial for other spinal cord injuries, the literature is mixed regarding the appropriate timing of surgery after ATCCS. Traditionally, this older population has been treated with delayed surgery because medical optimization is often indicated preoperatively. Surgically treated patients with ATCCS in the National Trauma Data Bank Research Data Set from 2011 and 2012 were identified. Time to surgery, Charlson Comorbidity Index, and injury severity scores were tested for association with mortality, serious adverse events, and minor adverse events using multivariate logistic regression. A total of 1060 patients with ATCCS met inclusion criteria. After controlling for pre-existing comorbidity and injury severity, delayed surgery was associated with a decreased odds of inpatient mortality (odds ratio = 0.81, P = 0.04), or a 19% decrease in odds of mortality with each 24-hour increase in time until surgery. The association of time to surgery with serious adverse events was not statistically significant (P = 0.09), whereas time to surgery was associated with increased odds of minor adverse events (odds ratio = 1.06, P < 0.001). Although the potential neurological effect of surgical timing for patients with ATCCS remains controversial, the decreased mortality with delayed surgery suggests that waiting to optimize general health and potentially allow for some spinal cord recovery in these patients may be advantageous. 3.

The NASA broad-specification fuels combustion technology program: An assessment of phase 1 test results

NASA Technical Reports Server (NTRS)

Fear, J. S.

1983-01-01

An assessment is made of the results of Phase 1 screening testing of current and advanced combustion system concepts using several broadened-properties fuels. The severity of each of several fuels-properties effects on combustor performance or liner life is discussed, as well as design techniques with the potential to offset these adverse effects. The selection of concepts to be pursued in Phase 2 refinement testing is described. This selection takes into account the relative costs and complexities of the concepts, the current outlook on pollutant emissions control, and practical operational problems.

A Prospective, Open-Label, Observational, Postmarket Study Evaluating VYC-17.5L for the Correction of Moderate to Severe Nasolabial Folds Over 12 Months

PubMed Central

Sattler, Gerhard; Philipp-Dormston, Wolfgang G.; Van Den Elzen, Helga; Van Der Walt, Cornelius; Nathan, Myooran; Kerson, Graeme; Dhillon, Benjeev

2017-01-01

BACKGROUND VYC-17.5L (17.5 mg/mL hyaluronic acid, 0.3% lidocaine) is a dermal filler intended for deep dermis injection for the treatment of skin depressions. OBJECTIVE To evaluate 12-month effectiveness and safety of VYC-17.5L for the treatment of moderate/severe nasolabial folds (NLFs). METHODS Subjects ≥18 years old with moderate/severe NLFs were recruited (N = 70). Injected volume was aimed at achieving optimum correction; top-up treatment was given at 2 weeks if needed. The primary endpoint was investigator-assessed change in NLF severity over 12 months using the validated photonumeric NLF Severity Scale. Secondary endpoints included investigator- and subject-assessed satisfaction and safety. Adverse events judged to be more severe or prolonged than routinely observed were recorded. RESULTS Sixty-five subjects completed study requirements. Mean volume injected was 3.0 ± 1.0 mL for both NLFs combined. Significant improvement was maintained in investigator-assessed NLF severity at 12 months, and investigators and subjects reported high satisfaction with VYC-17.5L throughout the study. Two unexpected adverse events were reported: (1) redness, swelling, and decreased sensitivity (resolved after 4 days) and (2) swelling (resolved after 48 hours); neither event was serious or life threatening. CONCLUSION VYC-17.5L is effective and well tolerated for the treatment of moderate to severe NLFs for 1 year. PMID:28165349

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

PubMed

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

2017-06-01

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

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real-world setting.

PubMed

Seaquist, Elizabeth R; Dulude, Hélène; Zhang, Xiaotian M; Rabasa-Lhoret, Remi; Tsoukas, George M; Conway, James R; Weisnagel, Stanley J; Gerety, Gregg; Woo, Vincent C; Zhang, Shuyu; Carballo, Dolorès; Pradhan, Sheetal; Piché, Claude A; Guzman, Cristina B

2018-05-01

In the present multicentre, open-label, prospective, phase III study, we evaluated the real-world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3-mg dose of NG demonstrated real-life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Antidepressant use in the elderly: the role of pharmacodynamics and pharmacokinetics in drug safety.

PubMed

Sultana, Janet; Spina, Edoardo; Trifirò, Gianluca

2015-06-01

Antidepressants (ADs) are widely used among elderly persons, making AD-related safety an important issue. This review highlights safety considerations related to AD use including risks associated with inappropriate and off-label use. The age-related pharmacokinetic and pharmacodynamic changes underlying safety concerns connected to ADs are outlined. Drug-drug interactions as a cause of AD-related adverse drug reactions (ADRs) are also discussed. We reviewed scientific evidence concerning three important safety outcomes related to ADs in elderly persons: cardiac arrhythmias, hyponatraemia and falls/fractures. Several AD-related ADRs in elderly people are likely to be preventable. Current evidence suggests that selective serotonin re-uptake inhibitors (SSRIs) are best avoided particularly in persons with kidney disease due to the risk of hyponatraemia. The use of tricyclic antidepressants (TCAs) should be limited in the elderly due to anticholinergic adverse effects. TCAs should also be avoided in elderly persons at high risk of cardiovascular events due to a risk of cardiac arrhythmia. Emerging evidence suggests that SSRIs also have arrhythmogenic potential. Both TCAs and SSRIs should be used cautiously in elderly persons at risk of falls. Future research in this area should aim to investigate the lowest effective dose of AD possible, the relationship between AD dose and adverse effects, and which elderly subgroups are most prone to develop severe ADRs.

Using human genetics to predict the effects and side-effects of drugs.

PubMed

Stender, Stefan; Tybjærg-Hansen, Anne

2016-04-01

'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. LDL cholesterol lowering variants in HMG-Coenzyme A reductase and Niemann-Pick C1-like protein 1, the targets for statins and ezetimibe, protect against ischemic heart disease (IHD). However, HMG-Coenzyme A reductase and Niemann-Pick C1-Like Protein 1-variants also increase the risk of type 2 diabetes and gallstone disease, respectively. Mutations in proprotein convertase subtilisin kexin 9 (PCSK9), apolipoprotein B, and microsomal triglyceride transfer protein cause low LDL cholesterol and protect against IHD. In addition, mutations in apolipoprotein B and microsomal triglyceride transfer protein cause hepatic steatosis, in concordance with drugs that inhibit these targets. Both mutations in PCSK9 and PCSK9-inhibition seem without adverse effects. Mutations in APOC3 cause low triglycerides and protect against IHD, and recent pharmacological APOC3-inhibition reported major reductions in plasma triglycerides. Human genetics support that low lipoprotein(a) protects against IHD, without adverse effects, and the first trial of lipoprotein(a) inhibition reduced lipoprotein(a) up to 78%. Recent genetic studies have confirmed the efficacy of statins and ezetimibe in protecting against IHD. Results from human genetics support that several lipid-lowering drugs currently under development are likely to prove efficacious in protecting against IHD, without major adverse effects.

ONTOGENY OF PROTEINS FOR USE AS BIOMARKERS OF DEVELOPMENTAL NEUROTOXICITY.

EPA Science Inventory

The developing nervous system can be uniquely susceptible to adverse effects following exposure to environmental chemicals, and several advisory panels (e.g. ILSI, NRC, NAS) have highlighted the need for rapid and sensitive developmental neurotoxicity testing methods. Measurement...

ZINC-DEFICIENCY ENHANCES PRO-INFLAMMATORY RESPONSES AFTER OZONE EXPOSURE

EPA Science Inventory

Epidemiological and controlled exposure studies have demonstrated that humans are differentially susceptible to adverse health effects induced by exposure to ozone. Serum analysis of vitamins and trace elements have shown that the elderly (people >65 years) are deficient in sever...

INTERACTION OF ORGANOPHOSPHATE PESTICIDES AND RELATED COMPOUNDS WITH THE ANDROGEN RECEPTOR

EPA Science Inventory

Identification of several environmental chemicals capable of binding to the androgen receptor (AR) and interfering with its normal function has heightened concern for adverse effects across a broad spectrum of environmental chemicals. We previously demonstrated AR antagonist act...

You make me sick: marital quality and health over the life course.

PubMed

Umberson, Debra; Williams, Kristi; Powers, Daniel A; Liu, Hui; Needham, Belinda

2006-03-01

We work from a life course perspective and identify several reasons to expect age and gender differences in the link between marital quality and health. We present growth curve evidence from a national longitudinal survey to show that marital strain accelerates the typical decline in self-rated health that occurs over time and that this adverse effect is greater at older ages. These findings fit with recent theoretical work on cumulative adversity in that marital strain seems to have a cumulative effect on health over time-an effect that produces increasing vulnerability to marital strain with age. Contrary to expectations, marital quality seems to affect the health of men and women in similar ways across the life course.

A systematic review of yoga for major depressive disorder.

PubMed

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

2017-04-15

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

Effects of benefits and harms on older persons' willingness to take medication for primary cardiovascular prevention.

PubMed

Fried, Terri R; Tinetti, Mary E; Towle, Virginia; O'Leary, John R; Iannone, Lynne

2011-05-23

Quality-assurance initiatives encourage adherence to evidenced-based guidelines based on a consideration of treatment benefit. We examined older persons' willingness to take medication for primary cardiovascular disease prevention according to benefits and harms. In-person interviews were performed with 356 community-living older persons. Participants were asked about their willingness to take medication for primary prevention of myocardial infarction (MI) with varying benefits in terms of absolute 5-year risk reduction and varying harms in terms of type and severity of adverse effects. Most (88%) would take medication, providing an absolute benefit of 6 fewer persons with MI out of 100, approximating the average risk reduction of currently available medications. Of participants who would not take it, 17% changed their preference if the absolute benefit was increased to 10 fewer persons with MI, and, of participants who would take it, 82% remained willing if the absolute benefit was decreased to 3 fewer persons with MI. In contrast, large proportions (48%-69%) were unwilling or uncertain about taking medication with average benefit causing mild fatigue, nausea, or fuzzy thinking, and only 3% would take medication with adverse effects severe enough to affect functioning. Older persons' willingness to take medication for primary cardiovascular disease prevention is relatively insensitive to its benefit but highly sensitive to its adverse effects. These results suggest that clinical guidelines and decisions about prescribing these medications to older persons need to place emphasis on both benefits and harms.

Acupuncture for depression.

PubMed

Smith, Caroline A; Armour, Mike; Lee, Myeong Soo; Wang, Li-Qiong; Hay, Phillipa J

2018-03-04

Depression is recognised as a major public health problem that has a substantial impact on individuals and on society. People with depression may consider using complementary therapies such as acupuncture, and an increasing body of research has been undertaken to assess the effectiveness of acupuncture for treatment of individuals with depression. This is the second update of this review. To examine the effectiveness and adverse effects of acupuncture for treatment of individuals with depression.To determine:• Whether acupuncture is more effective than treatment as usual/no treatment/wait list control for treating and improving quality of life for individuals with depression.• Whether acupuncture is more effective than control acupuncture for treating and improving quality of life for individuals with depression.• Whether acupuncture is more effective than pharmacological therapies for treating and improving quality of life for individuals with depression.• Whether acupuncture plus pharmacological therapy is more effective than pharmacological therapy alone for treating and improving quality of life for individuals with depression.• Whether acupuncture is more effective than psychological therapies for treating and improving quality of life for individuals with depression.• Adverse effects of acupuncture compared with treatment as usual/no treatment/wait list control, control acupuncture, pharmacological therapies, and psychological therapies for treatment of individuals with depression. We searched the following databases to June 2016: Cochrane Common Mental Disorders Group Controlled Trials Register (CCMD-CTR), Korean Studies Information Service System (KISS), DBPIA (Korean article database website), Korea Institute of Science and Technology Information, Research Information Service System (RISS), Korea Med, Korean Medical Database (KM base), and Oriental Medicine Advanced Searching Integrated System (OASIS), as well as several Korean medical journals. Review criteria called for inclusion of all published and unpublished randomised controlled trials comparing acupuncture versus control acupuncture, no treatment, medication, other structured psychotherapies (cognitive-behavioural therapy, psychotherapy, or counselling), or standard care. Modes of treatment included acupuncture, electro-acupuncture, and laser acupuncture. Participants included adult men and women with depression diagnosed by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), Research Diagnostic Criteria (RDC), International Statistical Classification of Diseases and Related Health Problems (ICD), or Chinese Classification of Mental Disorders Third Edition Revised (CCMD-3-R). If necessary, we used trial authors' definitions of depressive disorder. We performed meta-analyses using risk ratios (RRs) for dichotomous outcomes and standardised mean differences (SMDs) for continuous outcomes, with 95% confidence intervals (CIs). Primary outcomes were reduction in the severity of depression, measured by self-rating scales or by clinician-rated scales, and improvement in depression, defined as remission versus no remission. We assessed evidence quality using the GRADE method. This review is an update of previous versions and includes 64 studies (7104 participants). Most studies were at high risk of performance bias, at high or unclear risk of detection bias, and at low or unclear risk of selection bias, attrition bias, reporting bias, and other bias.Acupuncture versus no treatment/wait list/treatment as usualWe found low-quality evidence suggesting that acupuncture (manual and electro-) may moderately reduce the severity of depression by end of treatment (SMD -0.66, 95% CI -1.06 to -0.25, five trials, 488 participants). It is unclear whether data show differences between groups in the risk of adverse events (RR 0.89, 95% CI 0.35 to 2.24, one trial, 302 participants; low-quality evidence).Acupuncture versus control acupuncture (invasive, non-invasive sham controls)Acupuncture may be associated with a small reduction in the severity of depression of 1.69 points on the Hamilton Depression Rating Scale (HAMD) by end of treatment (95% CI -3.33 to -0.05, 14 trials, 841 participants; low-quality evidence). It is unclear whether data show differences between groups in the risk of adverse events (RR 1.63, 95% CI 0.93 to 2.86, five trials, 300 participants; moderate-quality evidence).Acupuncture versus medicationWe found very low-quality evidence suggesting that acupuncture may confer small benefit in reducing the severity of depression by end of treatment (SMD -0.23, 95% CI -0.40 to -0.05, 31 trials, 3127 participants). Studies show substantial variation resulting from use of different classes of medications and different modes of acupuncture stimulation. Very low-quality evidence suggests lower ratings of adverse events following acupuncture compared with medication alone, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) (mean difference (MD) -4.32, 95% CI -7.41 to -1.23, three trials, 481 participants).Acupuncture plus medication versus medication aloneWe found very low-quality evidence suggesting that acupuncture is highly beneficial in reducing the severity of depression by end of treatment (SMD -1.15, 95% CI -1.63 to -0.66, 11 trials, 775 participants). Studies show substantial variation resulting from use of different modes of acupuncture stimulation. It is unclear whether differences in adverse events are associated with different modes of acupuncture (SMD -1.32, 95% CI -2.86 to 0.23, three trials, 200 participants; very low-quality evidence).Acupuncture versus psychological therapyIt is unclear whether data show differences between acupuncture and psychological therapy in the severity of depression by end of treatment (SMD -0.5, 95% CI -1.33 to 0.33, two trials, 497 participants; low-quality evidence). Low-quality evidence suggests no differences between groups in rates of adverse events (RR 0.62, 95% CI 0.29 to 1.33, one trial, 452 participants). The reduction in severity of depression was less when acupuncture was compared with control acupuncture than when acupuncture was compared with no treatment control, although in both cases, results were rated as providing low-quality evidence. The reduction in severity of depression with acupuncture given alone or in conjunction with medication versus medication alone is uncertain owing to the very low quality of evidence. The effect of acupuncture compared with psychological therapy is unclear. The risk of adverse events with acupuncture is also unclear, as most trials did not report adverse events adequately. Few studies included follow-up periods or assessed important outcomes such as quality of life. High-quality randomised controlled trials are urgently needed to examine the clinical efficacy and acceptability of acupuncture, as well as its effectiveness, compared with acupuncture controls, medication, or psychological therapies.

Arrhythmogenicity of weight-loss supplements marketed on the Internet.

PubMed

Nazeri, Alireza; Massumi, Ali; Wilson, James M; Frank, Christopher M; Bensler, Michael; Cheng, Jie; Saeed, Mohammad; Rasekh, Abdi; Razavi, Mehdi

2009-05-01

We examined nonprescription weight-loss supplements marketed on the Internet for ingredients with potential arrhythmogenic and life-threatening cardiac adverse effects. We aimed to define the risks of life-threatening cardiac adverse effects that are associated with weight-loss supplements marketed on the Internet. We entered the key words "weight-loss supplements" and "diet pills" into three popular Internet search engines. The top four nonoverlapping hits from each search engine were purchased. After receipt, the products and their ingredient lists were inspected, and Medline and the Natural Medicines Comprehensive Database were searched for reports of significant associations between each ingredient and various key words for life-threatening cardiac adverse effects. All supplements had the list of ingredients on the label. We identified 60 different ingredients (7.25 +/- 4.66 per supplement; range 1-21). Eleven ingredients representing eight different substances (because multiple names were used for some substances) were each associated with two or more reports of life-threatening cardiac complications or death. Eight of the 12 products contained one or more such ingredients, but none of these eight products had warnings about life-threatening cardiac adverse effects on the Web pages, on the labels, or in the package inserts. One product contained ma huang (Chinese ephedra), even though the marketing of ephedra-containing products is banned in the United States. The Internet provides easy access to weight-loss supplements, several of which contain ingredients with potentially life-threatening adverse effects. There is a need for increased public education and awareness regarding such weight-loss products.

Dietary Fats and Health: Dietary Recommendations in the Context of Scientific Evidence1

PubMed Central

Lawrence, Glen D.

2013-01-01

Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking. PMID:23674795

Is imiquimod effective and safe for actinic keratosis?

PubMed

Walker, J Kendall; Koenig, Clint

2003-03-01

Imiquimod 5% cream, applied 3 times per week for 12 weeks, is effective for treatment of actinic keratosis. Severe erythema and other local reactions occurred in almost everyone receiving treatment, due to imiquimod's immune system-modulating effects. The 25 patients in the treatment group tolerated these adverse effects well. Despite these effects, imiquimod can be used as an alternative to traditional cryotherapy for the treatment of actinic keratosis among selected, motivated

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

PubMed Central

Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

2014-01-01

Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

PubMed

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

Adverse effect versus quality control of the Fuenzalida-Palacios antirabies vaccine.

PubMed

Nogueira, Y L

1998-01-01

We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post-vaccination neuroparalytic accident associated with Guillain-Barré syndrome. In the present study we demonstrate how the vaccines produced and distributed by different laboratories show different component patterns with different degrees of impurity and with varying protein concentrations, indicating that production processes can vary from one laboratory to another. These differences, which could be resolved using a better quality control process, may affect and impair immunization, with consequent risks and adverse effects after vaccination. We used crossed immunoelectrophoresis to evaluate and demonstrate the possibility of quality control in vaccine production, reducing the risk factors possibly involved in these immunizing products.

Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior.

PubMed

Tielbeek, Jorim J; Karlsson Linnér, Richard; Beers, Koko; Posthuma, Danielle; Popma, Arne; Polderman, Tinca J C

2016-07-01

Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

PubMed Central

Makowska, Joanna S.

2015-01-01

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management. PMID:25749768

Are High-Severity Fires Burning at Much Higher Rates Recently than Historically in Dry-Forest Landscapes of the Western USA?

PubMed

Baker, William L

2015-01-01

Dry forests at low elevations in temperate-zone mountains are commonly hypothesized to be at risk of exceptional rates of severe fire from climatic change and land-use effects. Their setting is fire-prone, they have been altered by land-uses, and fire severity may be increasing. However, where fires were excluded, increased fire could also be hypothesized as restorative of historical fire. These competing hypotheses are not well tested, as reference data prior to widespread land-use expansion were insufficient. Moreover, fire-climate projections were lacking for these forests. Here, I used new reference data and records of high-severity fire from 1984-2012 across all dry forests (25.5 million ha) of the western USA to test these hypotheses. I also approximated projected effects of climatic change on high-severity fire in dry forests by applying existing projections. This analysis showed the rate of recent high-severity fire in dry forests is within the range of historical rates, or is too low, overall across dry forests and individually in 42 of 43 analysis regions. Significant upward trends were lacking overall from 1984-2012 for area burned and fraction burned at high severity. Upward trends in area burned at high severity were found in only 4 of 43 analysis regions. Projections for A.D. 2046-2065 showed high-severity fire would generally be still operating at, or have been restored to historical rates, although high projections suggest high-severity fire rotations that are too short could ensue in 6 of 43 regions. Programs to generally reduce fire severity in dry forests are not supported and have significant adverse ecological impacts, including reducing habitat for native species dependent on early-successional burned patches and decreasing landscape heterogeneity that confers resilience to climatic change. Some adverse ecological effects of high-severity fires are concerns. Managers and communities can improve our ability to live with high-severity fire in dry forests.

Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.

PubMed

Wu, Min; Xiao, Guang-hua; Yao, Min; Zhang, Jian-ming; Zhang, Xin; Zhou, Ya-bing; Zhang, Jing-yan; Wang, Shu-xia; Ma, Bo; Chen, Yan-ping

2009-08-01

To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.

Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative cheilitis.

PubMed

Bhatia, Bhavnit K; Bahr, Brooks A; Murase, Jenny E

2015-06-01

Exfoliative cheilitis is a condition of unknown etiology characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic desquamation. It remains largely refractory to treatment, including corticosteroid therapy, antibiotics, antifungals, and immunosuppressants. We sought to evaluate the safety and efficacy of excimer laser therapy and narrowband ultraviolet B therapy in female patients with refractory exfoliative cheilitis. We reviewed the medical records of two female patients who had been treated unsuccessfully for exfoliative cheilitis. We implemented excimer laser therapy, followed by hand-held narrowband UVB treatments for maintenance therapy, and followed them for clinical improvement and adverse effects. Both patients experienced significant clinical improvement with minimal adverse effects with excimer laser therapy 600-700 mJ/cm 2 twice weekly for several months. The most common adverse effects were bleeding and burning, which occurred at higher doses. The hand-held narrowband UVB unit was also an effective maintenance tool. Limitations include small sample size and lack of standardization of starting dose and dose increments. Excimer laser therapy is a well-tolerated and effective treatment for refractory exfoliative cheilitis with twice weekly laser treatments of up to 700 mJ/cm 2 . Transitioning to the hand-held narrowband UVB device was also an effective maintenance strategy.

ADVERSE EFFECTS OF ENVIRONMENTAL ANTIANDROGENS AND ANDROGENS ON REPRODUCTIVE DEVELOPMENT IN MAMMALS

EPA Science Inventory

Within the last decade, several classes of chemicals have been shown in laboratory studies to disrupt reproductive development by acting as androgen receptor (AR) antagonists and/or inhibitors of fetal Leydig cell testosterone production. Some phthalate esters alter gubernacular...

THE USE OF INSITU TREATMENT TO REDUCE TOXICITY

EPA Science Inventory

Mining or smelting of lead and zinc ores generates mine tailing and smelter slags rich in lead, zinc, and cadmium. Old smelting operations have commonly caused severly contaminated sites and adverse effects in the terrestrial environment. Research has clarified the causes of s...

Sediment Toxicity Identification Evaluations (TIEs): Manipulating Bioavailability to Whole Organisms to Identify Environmental Toxins

EPA Science Inventory

Toxicity tests are a common method for determining whether sediment contaminants represent an environmental risk. Toxicity tests indicate if contaminants in sediments are bioavailable and capable of causing adverse biological effects to whole aquatic organisms. Several environmen...

NEW APPROACHES AND TOOLS FOR THE CONDUCT OF COMMUNITY-BASED CUMULATIVE RISK ASSESSMENTS

EPA Science Inventory

Individuals have differential exposures and potential risk of adverse health effects, regardless of whether chemical exposure occurs singly or as mixtures of several chemicals. Elevated exposures can result from frequent contact with environmental contaminants and depends on the...

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

PubMed

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

2017-08-01

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

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

PubMed Central

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

2017-01-01

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

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

PubMed

Wang, Chuang-Wei; Yang, Lan-Yan; Chen, Chun-Bing; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chang, Ya-Ching; Lu, Chun-Wei; Chung, Wen-Hung

2018-03-01

Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. ClinicalTrials.gov NCT01276314. Ministry of Science and Technology of Taiwan.

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

PubMed Central

Wang, Chuang-Wei; Yang, Lan-Yan; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chung, Wen-Hung

2018-01-01

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan. PMID:29400697

Severity of mental illness as a result of multiple childhood adversities: US National Epidemiologic Survey.

PubMed

Curran, Emma; Adamson, Gary; Stringer, Maurice; Rosato, Michael; Leavey, Gerard

2016-05-01

To examine patterns of childhood adversity, their long-term consequences and the combined effect of different childhood adversity patterns as predictors of subsequent psychopathology. Secondary analysis of data from the US National Epidemiologic Survey on alcohol and related conditions. Using latent class analysis to identify childhood adversity profiles; and using multinomial logistic regression to validate and further explore these profiles with a range of associated demographic and household characteristics. Finally, confirmatory factor analysis substantiated initial latent class analysis findings by investigating a range of mental health diagnoses. Latent class analysis generated a three-class model of childhood adversity in which 60 % of participants were allocated to a low adversity class; 14 % to a global adversities class (reporting exposures for all the derived latent classes); and 26 % to a domestic emotional and physical abuse class (exposed to a range of childhood adversities). Confirmatory Factor analysis defined an internalising-externalising spectrum to represent lifetime reporting patterns of mental health disorders. Using logistic regression, both adversity groups showed specific gender and race/ethnicity differences, related family discord and increased psychopathology. We identified underlying patterns in the exposure to childhood adversity and associated mental health. These findings are informative in their description of the configuration of adversities, rather than focusing solely on the cumulative aspect of experience. Amelioration of longer-term negative consequences requires early identification of psychopathology risk factors that can inform protective and preventive interventions. This study highlights the utility of screening for childhood adversities when individuals present with symptoms of psychiatric disorders.

Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers.

PubMed

Kohrt, Brandon A; Worthman, Carol M; Adhikari, Ramesh P; Luitel, Nagendra P; Arevalo, Jesusa M G; Ma, Jeffrey; McCreath, Heather; Seeman, Teresa E; Crimmins, Eileen M; Cole, Steven W

2016-07-19

Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.

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

Kastenberg, W.E.; Apostolakis, G.; Dhir, V.K.

Severe accident management can be defined as the use of existing and/or altemative resources, systems and actors to prevent or mitigate a core-melt accident. For each accident sequence and each combination of severe accident management strategies, there may be several options available to the operator, and each involves phenomenological and operational considerations regarding uncertainty. Operational uncertainties include operator, system and instrumentation behavior during an accident. A framework based on decision trees and influence diagrams has been developed which incorporates such criteria as feasibility, effectiveness, and adverse effects, for evaluating potential severe accident management strategies. The framework is also capable ofmore » propagating both data and model uncertainty. It is applied to several potential strategies including PWR cavity flooding, BWR drywell flooding, PWR depressurization and PWR feed and bleed.« less

Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers.

PubMed

Yao, Guiqing Lily; Novielli, Nicola; Manaseki-Holland, Semira; Chen, Yen-Fu; van der Klink, Marcel; Barach, Paul; Chilton, Peter J; Lilford, Richard J

2012-12-01

We developed a method to estimate the expected cost-effectiveness of a service intervention at the design stage and 'road-tested' the method on an intervention to improve patient handover of care between hospital and community. The development of a nine-step evaluation framework: 1. Identification of multiple endpoints and arranging them into manageable groups; 2. Estimation of baseline overall and preventable risk; 3. Bayesian elicitation of expected effectiveness of the planned intervention; 4. Assigning utilities to groups of endpoints; 5. Costing the intervention; 6. Estimating health service costs associated with preventable adverse events; 7. Calculating health benefits; 8. Cost-effectiveness calculation; 9. Sensitivity and headroom analysis. Literature review suggested that adverse events follow 19% of patient discharges, and that one-third are preventable by improved handover (ie, 6.3% of all discharges). The intervention to improve handover would reduce the incidence of adverse events by 21% (ie, from 6.3% to 4.7%) according to the elicitation exercise. Potentially preventable adverse events were classified by severity and duration. Utilities were assigned to each category of adverse event. The costs associated with each category of event were obtained from the literature. The unit cost of the intervention was €16.6, which would yield a Quality Adjusted Life Year (QALY) gain per discharge of 0.010. The resulting cost saving was €14.3 per discharge. The intervention is cost-effective at approximately €214 per QALY under the base case, and remains cost-effective while the effectiveness is greater than 1.6%. We offer a usable framework to assist in ex ante health economic evaluations of health service interventions.

Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers

PubMed Central

Yao, Guiqing Lily; Novielli, Nicola; Manaseki-Holland, Semira; Chen, Yen-Fu; van der Klink, Marcel; Barach, Paul; Chilton, Peter J; Lilford, Richard J

2012-01-01

Background We developed a method to estimate the expected cost-effectiveness of a service intervention at the design stage and ‘road-tested’ the method on an intervention to improve patient handover of care between hospital and community. Method The development of a nine-step evaluation framework: 1. Identification of multiple endpoints and arranging them into manageable groups; 2. Estimation of baseline overall and preventable risk; 3. Bayesian elicitation of expected effectiveness of the planned intervention; 4. Assigning utilities to groups of endpoints; 5. Costing the intervention; 6. Estimating health service costs associated with preventable adverse events; 7. Calculating health benefits; 8. Cost-effectiveness calculation; 9. Sensitivity and headroom analysis. Results     Literature review suggested that adverse events follow 19% of patient discharges, and that one-third are preventable by improved handover (ie, 6.3% of all discharges). The intervention to improve handover would reduce the incidence of adverse events by 21% (ie, from 6.3% to 4.7%) according to the elicitation exercise. Potentially preventable adverse events were classified by severity and duration. Utilities were assigned to each category of adverse event. The costs associated with each category of event were obtained from the literature. The unit cost of the intervention was €16.6, which would yield a Quality Adjusted Life Year (QALY) gain per discharge of 0.010. The resulting cost saving was €14.3 per discharge. The intervention is cost-effective at approximately €214 per QALY under the base case, and remains cost-effective while the effectiveness is greater than 1.6%. Conclusions We offer a usable framework to assist in ex ante health economic evaluations of health service interventions. PMID:22976505

Preventive effects of phytoestrogens against postmenopausal osteoporosis as compared to the available therapeutic choices: An overview

PubMed Central

Al-Anazi, Abdullah Foraih; Qureshi, Viquar Fatima; Javaid, Khalida; Qureshi, Shoeb

2011-01-01

Estrogen deficiency is a major risk factor for osteoporosis in postmenopausal women. Although hormone replacement therapy (HRT) has been rampantly used to recompense for the bone loss, but the procedure is coupled with severe adverse effects. Hence, there is a boost in the production of newer synthetic products to ward off the effects of menopause-related osteoporosis. As of today, there are several prescription products available for the treatment of postmenopause osteoporosis; most of these are estrogenic agents and combination products. Nevertheless, in view of the lack of effect and/or toxicity of these products, majority of the postmenopausal women are now fascinated by highly publicized natural products. This is an offshoot of the generalized consensus that these products are more effective and free from any adverse effects. Recently, certain plant-derived natural products, mostly phytoestrogens (isoflavones, lignans, coumestanes, stilbenes, flavonoids) and many more novel estrogen-like compounds in plants have been immensely used to prevent menopause-related depletion in bone mineral density (BMD). Although, a number of papers are published on menopause-related general symptoms, sexual dysfunction, cardiovascular diseases, Alzheimer's disease, diabetes, colon, and breast cancers, there is paucity of literature on the accompanying osteoporosis and its treatment. In view of the controversies on synthetic hormones and drugs and drift of a major population of patients toward natural drugs, it was found worthwhile to investigate if these drugs are suitable to be used in the treatment of postmenopausal osteoporosis. Preparation of this paper is an attempt to review the (a) epidemiology of postmenopausal osteoporosis, (b) treatment modalities of postmenopausal osteoporosis by hormones and synthetic drugs and the associated drawbacks and adverse effects, and (c) prevention and treatment of postmenopausal osteoporosis by phytoestrogens, their drawbacks and toxicity. It is apparent that both the categories of treatment are useful and both have adverse effects, but the plant products are nonscientific and hence are not advised to be used till more studies are undertaken to ensure that the benefits clearly outweigh the risk, in addition to recognition by Food and Drug Administration. PMID:22346228

Storage and utilization patterns of cleaning products in the home: toxicity implications.

PubMed

Sawalha, Ansam F

2007-11-01

Cleaning products are used to achieve cleaner homes. However, they have been responsible for a considerable number of poisoning cases. The aims of this study were to investigate the storage and utilization patterns of cleaning products in the home, as well as the risk of adverse and toxic effects produced by them. This study has been performed using a questionnaire that was developed by the Poison Control and Drug Information Center (PCDIC). The questionnaire was distributed randomly in northern Palestine. The questionnaire included questions regarding storage, utilization habits, and the adverse effects experienced by respondents upon handling the cleaning products. All respondents utilized and stored cleaning products in their homes. Chlorine bleach and acidic cleaning products were the most common. Respondents stored cleaning products at different places in their homes, but most of those storage places were suboptimal and were within the reach of children. The daily utilization rate of cleaning products was 1.6+/-0.8 with chlorine bleach being the most commonly used. Of the respondents, 27% reported experiencing a wide range of acute adverse and toxic effects resulting from cleaning product use and that exposure occurred mainly via inhalation. Caustic substances, bleach, and kerosene were the agents mainly involved in producing these adverse and toxic effects. About half of those who experienced adverse and toxic effects sought medical help, and 22% of them were children younger than 6 years of age. Finally, most respondents reported mixing and discarding cleaning product leftovers and their containers improperly. Correct utilization and safer storage of cleaning products is encouraged. Several preventive strategies should be implemented in order to decrease the incidence of accidental harmful exposure that is due to cleaning agents. The role of the PCDIC is very important in the education, prevention, and management of cleaning product-induced adverse effects.

Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

PubMed

Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

2016-06-01

Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Late effects in childhood cancer survivors: a review with a framing effect bias?

PubMed

Fryer, Christopher

2011-12-15

Most publications report the adverse (negative) health issues in childhood cancer survivors. Presenting information to the newly diagnosed patient in a positive manner is advocated, while noting that recurrence is the most likely adverse event. Re-analysis of population-based studies on life-threatening toxicities from Nordic, Dutch, United Kingdom, French, Italian, and N. American publications shows that 5-year survivors have a near normal life expectancy, 75% have no severe or life-threatening treatment related toxicity and 87% remain free of a second malignancy. Children who received radiation or anthracycline >250-300 mg/m(2) are at greatest risk for treatment related life-threatening toxicities. Copyright © 2011 Wiley Periodicals, Inc.

The K2/Spice Phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products

PubMed Central

Brents, Lisa K.; Prather, Paul L.

2014-01-01

In 2008, the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) detected unregulated, psychoactive synthetic cannabinoids (SCBs) in purportedly all-natural herbal incense products (often known as K2 or Spice) that were being covertly abused as marijuana substitutes. These drugs, which include JWH-018, JWH-073 and CP-47,497, bind and activate the cannabinoid receptors CB1R and CB2R with remarkable potency and efficacy. Serious adverse effects that often require medical attention, including severe cardiovascular, gastrointestinal and psychiatric sequelae, are highly prevalent with SCB abuse. Consequently, progressively restrictive legislation in the US and Europe has banned the distribution, sale and use of prevalent SCBs, initiating cycles in which herbal incense manufacturers replace banned SCBs with newer unregulated SCBs. The contents of the numerous, diverse herbal incense products was unknown when SCB abuse first emerged. Furthermore, the pharmacology of the active components was largely uncharacterized, and confirmation of SCB use was hindered by a lack of known biomarkers. These knowledge gaps prompted scientists across multiple disciplines to rapidly (1) monitor, identify and quantify with chromatography/mass spectrometry the ever-changing contents of herbal incense products, (2) determine the metabolic pathways and major urinary metabolites of several commonly abused SCBs and (3) identify active metabolites that possibly contribute to the severe adverse effect profile of SCBs. This review comprehensively describes the emergence of SCB abuse and provides a historical account of the major case reports, legal decisions and scientific discoveries of the ″K2/Spice Phenomenon″. Hypotheses concerning potential mechanisms SCB adverse effects are proposed in this review. PMID:24063277

U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation.

PubMed

Dewey, Kathryn G; Oaks, Brietta M

2017-12-01

Both iron deficiency (ID) and excess can lead to impaired health status. There is substantial evidence of a U-shaped curve between the risk of adverse birth outcomes and maternal hemoglobin concentrations during pregnancy; however, it is unclear whether those relations are attributable to conditions of low and high iron status or to other mechanisms. We summarized current evidence from human studies regarding the association between birth outcomes and maternal hemoglobin concentrations or iron status. We also reviewed effects of iron supplementation on birth outcomes among women at low risk of ID and the potential mechanisms for adverse effects of high iron status during pregnancy. Overall, we confirmed a U-shaped curve for the risk of adverse birth outcomes with maternal hemoglobin concentrations, but the relations differ by trimester. For low hemoglobin concentrations, the link with adverse outcomes is more evident when hemoglobin concentrations are measured in early pregnancy. These relations generally became weaker or nonexistent when hemoglobin concentrations are measured in the second or third trimesters. Associations between high hemoglobin concentration and adverse birth outcomes are evident in all 3 trimesters but evidence is mixed. There is less evidence for the associations between maternal iron status and adverse birth outcomes. Most studies used serum ferritin (SF) concentrations as the indicator of iron status, which makes the interpretation of results challenging because SF concentrations increase in response to inflammation or infection. The effect of iron supplementation during pregnancy may depend on initial iron status. There are several mechanisms through which high iron status during pregnancy may have adverse effects on birth outcomes, including oxidative stress, increased blood viscosity, and impaired systemic response to inflammation and infection. Research is needed to understand the biological processes that underlie the U-shaped curves seen in observational studies. Reevaluation of cutoffs for hemoglobin concentrations and indicators of iron status during pregnancy is also needed. © 2017 American Society for Nutrition.

Gulf Coast Deep Water Port Facilities Study. Environmental Assessment.

DTIC Science & Technology

1973-04-01

contributions of our consultants - Dr. George L. Clarke, Harvard Univer- sity; Dr. Bostwick H. Ketchum, Woods Hole Oceanographic Institution; and Dr...NATURE OF ADVERSE ENVIRONMENTAL EFFECTS A. TERMINAL CONSTRUCTION Rounsefell (1972) has recently reviewed the potential ecological effects of offshore...area for a variety of avian and mammalian forms, the effects of oil spills on these regions are particularly severe. The ecological chain of depen

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

PubMed

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

2016-04-25

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

Statistical process control methods allow the analysis and improvement of anesthesia care.

PubMed

Fasting, Sigurd; Gisvold, Sven E

2003-10-01

Quality aspects of the anesthetic process are reflected in the rate of intraoperative adverse events. The purpose of this report is to illustrate how the quality of the anesthesia process can be analyzed using statistical process control methods, and exemplify how this analysis can be used for quality improvement. We prospectively recorded anesthesia-related data from all anesthetics for five years. The data included intraoperative adverse events, which were graded into four levels, according to severity. We selected four adverse events, representing important quality and safety aspects, for statistical process control analysis. These were: inadequate regional anesthesia, difficult emergence from general anesthesia, intubation difficulties and drug errors. We analyzed the underlying process using 'p-charts' for statistical process control. In 65,170 anesthetics we recorded adverse events in 18.3%; mostly of lesser severity. Control charts were used to define statistically the predictable normal variation in problem rate, and then used as a basis for analysis of the selected problems with the following results: Inadequate plexus anesthesia: stable process, but unacceptably high failure rate; Difficult emergence: unstable process, because of quality improvement efforts; Intubation difficulties: stable process, rate acceptable; Medication errors: methodology not suited because of low rate of errors. By applying statistical process control methods to the analysis of adverse events, we have exemplified how this allows us to determine if a process is stable, whether an intervention is required, and if quality improvement efforts have the desired effect.

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis.

PubMed

Atkinson, Hayden F; Moyer, Rebecca F; Yacoub, Daniel; Coughlin, Dexter; Birmingham, Trevor B

2017-03-01

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Depressed patients in remission show an interaction between variance in the mineralocorticoid receptor NR3C2 gene and childhood trauma on negative memory bias.

PubMed

Vrijsen, Janna N; Vogel, Susanne; Arias-Vásquez, Alejandro; Franke, Barbara; Fernández, Guillén; Becker, Eni S; Speckens, Anne; van Oostrom, Iris

2015-06-01

Genetic, environmental, and cognitive factors play a role in the development and recurrence of depression. More specifically, cognitive biases have been associated with depression risk genes and life events. Recently, the mineralocorticoid receptor NR3C2 gene, and in particular the rs5534 polymorphism, has been associated with negative memory bias, at least in healthy individuals who experienced severe life adversity. The current study examined the interaction between the rs5534 genotype and different types of adverse life events in a sample of depressed patients in remission. A total of 298 depressed patients in remission performed an incidental emotional memory task (negative and positive words). Life adversity, childhood trauma, and recent adversity were measured using a self-report questionnaire. NR3C2 rs5534 by life adversity, as well as childhood trauma and recent adversity interactions were analyzed for negative and positive memory bias using analyses of covariance. The significant interaction between rs5534 and childhood trauma on negative memory bias (P=0.046) indicated that risk 'A' allele carriers with childhood trauma tended to show more negative memory bias compared to individuals homozygous for the G allele who had experienced childhood trauma and A allele carriers without childhood trauma. No interaction effects with life adversity or recent adversity were found. Also, no main effect of rs5534 on memory bias was found, although we had insufficient power for this analysis. An association of the NR3C2 gene and childhood trauma with negative memory bias was found in depressed patients in remission, which extends previous findings in a healthy population.

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

PubMed

Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

2010-12-01

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Roadside vegetation design characteristics that can improve local, near road air quality

EPA Science Inventory

As public health concerns have increased due to the rising number of studies linking adverse health effects with exposures to traffic-related pollution near large roadways, interest in methods to mitigate these exposures have also increased. Several studies have investigated the...

Comparison of hurricane exposure methods and associations with county fetal death rates, adjusting for environmental quality

EPA Science Inventory

Adverse effects of hurricanes are increasing as coastal populations grow and events become more severe. Hurricane exposure during pregnancy can influence fetal death rates through mechanisms related to healthcare, infrastructure disruption, nutrition, and injury. Estimation of hu...

Hazard identification of environmental pollutants by combining results from ecological and biomarker studies: an example

EPA Science Inventory

Objective: Linking exposures from environmental pollutants with adverse health effects is difficult because these exposures are usually low-dose and ill-defined. According to several investigators, a series of multidisciplinary, multilevel studies is needed to address this prob...

THE INFLUENCE OF A NOISE BARRIER AND VEGETATION ON AIR QUALITY NEAR A ROADWAY

EPA Science Inventory

A growing number of epidemiological studies conducted throughout the world have identified an increase in occurrence of adverse health effects for populations residing, working or attending school near major roadways. In addition, several air quality studies have identified incr...

Developing a Reference Material for Formaldehyde Emissions Testing; Final Report

EPA Science Inventory

Exposure to formaldehyde has been shown to produce broad and potentially severe adverse human health effects. With ubiquitous formaldehyde sources in the indoor environment, formaldehyde concentrations in indoor air are usually higher than outdoors, ranging from 10 to 4000 μg/m3....

Zinc Ions as Effectors of Environmental Oxidative Lung Injury

EPA Science Inventory

The non-redox active transition metal Zn is a micronutrient that plays essential roles in protein structure, catalysis and regulation of function. Inhalational exposure to ZnO or Zn salts in occupational and environmental settings leads to adverse health effects, the severity of ...

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

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

A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient.

PubMed

Araújo, Manuel; Ligeiro, Dário; Costa, Luís; Marques, Filipa; Trindade, Helder; Correia, José Manuel; Fonseca, Candida

2017-06-01

Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.

[Club drugs].

PubMed

Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

2011-01-01

Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

Killer artificial antigen-presenting cells: the synthetic embodiment of a ‘guided missile’

PubMed Central

Schütz, Christian; Oelke, Mathias; Schneck, Jonathan P; Mackensen, Andreas; Fleck, Martin

2010-01-01

At present, the treatment of T-cell-dependent autoimmune diseases relies exclusively on strategies leading to nonspecific suppression of the immune systems causing a substantial reduced ability to control concomitant infections or malignancies. Furthermore, long-term treatment with most drugs is accompanied by several serious adverse effects and does not consequently result in cure of the primary immunological malfunction. By contrast, antigen-specific immunotherapy offers the potential to achieve the highest therapeutic efficiency in accordance with minimal adverse effects. Therefore, several studies have been performed utilizing antigen-presenting cells specifically engineered to deplete allo- or antigen-specific T cells (‘guided missiles’). Many of these strategies take advantage of the Fas/Fas ligand signaling pathway to efficiently induce antigen-presenting cell-mediated apoptosis in targeted T cells. In this article, we discuss the advantages and shortcomings of a novel non-cell-based ‘killer artificial antigen-presenting cell’ strategy, developed to overcome obstacles related to current cell-based approaches for the treatment of T-cell-mediated autoimmunity. PMID:20636007

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

PubMed

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

2013-05-01

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

Drug packaging in 2013: small changes would reap big benefits.

PubMed

2014-05-01

Drug packaging is important both in protecting and informing patients. Some improvements were made in 2013, but many of the products examined by Prescrire still had poor-quality or even dangerous packaging. Problem packaging is a major concern for patients who are more vulnerable to adverse effects, particularly children and pregnant women. Several problems were noted with products intended for self-medication (umbrella brands), oral solutions sold with dosing devices, and injectable drugs. Looking back at 20 years of Red Cards that Prescrire has issued to products with dangerous packaging reveals several improvements, but too many dangers persist. Urgent action needs to be taken by regulatory agencies and drug companies: patient leaflets must be more explicit with regard to adverse effects, especially those of nonsteroidal anti-inflammatory drugs during pregnancy; accidental ingestion by children must be prevented; and companies must design safer dosing devices. Healthcare professionals and patients must remain vigilant and report all packaging issues to the relevant authorities.

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids-A Systematic Review.

PubMed

Cohen, Koby; Weinstein, Aviv

2018-02-27

Background-Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method-A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., "synthetic cannabinoids AND cognition," "cannabis AND cognition" and "cannabinoids AND cognition"). Results-The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions-Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs.

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review

PubMed Central

Cohen, Koby; Weinstein, Aviv

2018-01-01

Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”). Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs. PMID:29495540

Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects

PubMed Central

Long, Michelle; Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.

2013-01-01

In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years. PMID:22190130

Cannabis: an overview of its adverse acute and chronic effects and their implications.

PubMed

Ford, Talitha C; Hayley, Amie C; Downey, Luke A; Parrott, Andrew C

2017-07-12

In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. However, acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure. Although the cannabinoid cannabidiol (CBD) has been shown to have positive health outcomes with its antioxidant, anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low CDB concentration. It is this high-potency substance that is readily available recreationally. While pharmaceutical initiatives continue to investigate the medical benefits of CDB, "medicinal cannabis" still contains damaging levels of THC. Altogether, we argue there is insufficient evidence to support the safety of cannabis and its subsequent legalisation for recreational use. Furthermore, its use for medicinal purposes should be done with care. We argue that the public conversation for the legalisation of cannabis must include scientific evidence for its adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Encouraging CPAP adherence: it is everyone's job.

PubMed

Bollig, Suzanne M

2010-09-01

Obstructive sleep apnea (OSA) is a chronic disease treated effectively with the use of continuous positive airway pressure (CPAP) therapy. Patient adherence to prescribed CPAP is variable, however, leaving the undertreated OSA patient at risk of development or worsening of comorbid medical conditions, including hypertension and cardiovascular disease. The severity of disease and the presence of daytime sleepiness appear to have some predictive quality for subsequent adherence, though a search for consistent predictive factors related to CPAP adherence has proven elusive. Other influences, such as sex, age, socioeconomic status, and personality traits are less robust predictors. The use of sophisticated therapy modalities such as auto-titration or bi-level PAP units has been shown to improve adherence in certain subsets of OSA patients. Adverse effects such as nasal congestion, dry mouth, or skin irritation occur in approximately 50% of CPAP users, and addressing these adverse effects may improve adherence in some patients. More encouraging, studies on the use of intensive patient education and behavioral interventions have shown more positive effects on adherence, leading to the conclusion that improvement in patient adherence to CPAP therapy requires a multi-layered approach, using combined technological, behavioral, and adverse-effect interventions.

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

PubMed

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

2014-05-01

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

Complementary and alternative medicine for allergic rhinitis.

PubMed

Man, Li-Xing

2009-06-01

Otolaryngologists and other physicians who diagnose and treat allergic rhinitis encounter patients who use complementary medicine and alternative remedies. This article reviews the recent literature regarding complementary and alternative therapies for the treatment of allergic rhinitis. There are a myriad of modalities for treating allergic rhinitis. Few are studied with rigorous randomized, double-blind, placebo-controlled trials for clinical efficacy. Often, the biological mechanisms and adverse effects are even less well understood. A few therapies, including spirulina, butterbur, and phototherapy hold some promise. Thus far, complementary and alternative therapies have not been integrated into the general treatment armamentarium of allergic rhinitis. Several studies report beneficial effects of certain alternative treatments for allergic rhinitis. Additional insight into the mechanisms of action, short-term and long-term effects, and adverse events is needed.

Personalized Medicine and Adverse Drug Reactions: The Experience of An Italian Teaching Hospital.

PubMed

La Russa, Raffaele; Finesch, Vittorio; Di Sanzo, Mariantonia; Gatto, Vittorio; Santurro, Alessandro; Martini, Gabriella; Scopetti, Matteo; Frati, Paola

2017-01-01

The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years. Comparing the data result from our analysis with several studies found in literature, it is evident that adverse drug reactions represent an important problem in the management of a health care system. However, the development of pharmacogenetics and pharmacogenomics, allowing a personalized treatment, can improve clinical practice. This study highlights the great potential of pharmacogenomics in reducing adverse reactions and suggests the need for further pharmacogenomic clinical trials to better personalize drug treatment and to refine the current pharmacovigilance strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

Finch, Laura E; Tomiyama, A Janet

2015-12-01

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

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

PubMed

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

2018-04-25

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

Reasons for Energy Drink Use and Reported Adverse Effects Among Adolescent Emergency Department Patients.

PubMed

Nordt, Sean Patrick; Claudius, Ilene; Rangan, Cyrus; Armijo, Erick; Milano, Peter; Yanger, Sheryl; Tomaszsewski, Christian

2017-12-01

There is concern of energy drink use by adolescents. The objective of this study was to evaluate the energy drink consumption use, frequency, age of first use, reasons for use, influences of choice of brand, and adverse events recorded in a predominant Latino adolescent population. Subjects between the ages of 13 and 19 years utilizing emergency department services for any reason at a large county hospital answered a questionnaire about energy drink usage. There were 192 subjects, of which 49% were male and 51% were female. Latino adolescents were 85% of the participants, although other ethnic groups participated including African American, white, and Asian. Reasons for use include 61% to increase energy, 32% as study aide, 29% to improve sports performance, and 9% to lose weight. Twenty-four percent reported using energy drinks with ethanol or illicit drugs including marijuana, cocaine, and methamphetamine. Adverse reactions were reported in 40% of the subjects including insomnia (19%), feeling "jittery" (19%), palpitations (16%), gastrointestinal upset (11%), headache (8%), chest pain (5%), shortness of breath (4%), and seizures (1%). Both brand name and packaging influenced the choice of energy drink in most subjects. Forty percent reported at least 1 adverse effect. While most adverse effects were not severe, a small number are serious. In addition, we showed intentional ingestion with ethanol and illicit drugs. Of additional concern is that both brand and packaging seem to directly affect choice of energy drink consumed.

Effects of Bazedoxifene Alone and with Conjugated Equine Estrogens on Coronary and Peripheral Artery Atherosclerosis of Postmenopausal Monkeys

PubMed Central

Clarkson, Thomas B.; Ethun, Kelly F.; Chen, Haiying; Golden, Debbie; Floyd, Edison; Appt, Susan E.

2012-01-01

Objective The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Methods Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Results Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. Conclusions In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE. PMID:23435024

Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide

PubMed Central

Lheureux, Philippe ER; Zahir, Soheil; Penaloza, Andrea; Gris, Mireille

2005-01-01

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting. PMID:16356235

Antidepressant-selective gynecomastia.

PubMed

Kaufman, Kenneth R; Podolsky, Dina; Greenman, Danielle; Madraswala, Rehman

2013-01-01

To describe what we believe is the first reported case of synergistic gynecomastia during treatment of depressive and anxiety disorders when sertraline was added to a stable medication regimen including duloxetine, rosuvastatin, and amlodipine. A 67-year-old male with major depression, dysthymia, obsessive-compulsive disorder, social anxiety, hypertension, diabetes, and hyperlipidemia presented with new-onset gynecomastia and breast tenderness. Mammography revealed bilateral gynecomastia (fibroglandular tissue posterior to the nipples bilaterally) without suspicious mass, calcification, or other abnormalities. These new symptoms developed after sertraline was added to his stable medication regimen (duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, hydrochlorothiazide/triamterene, metformin, and sitagliptin). These symptoms were dose-dependent, with gynecomastia and breast tenderness more severe as sertraline was titrated from 25 mg/day to 50 mg/day and then to 75 mg/day. When sertraline was discontinued, gynecomastia and breast tenderness rapidly resolved. Mammoplasia and gynecomastia are associated with altered dopamine neurotransmission and/or perturbations in sexual hormones. These adverse effects may be medication induced. Selective serotonin reuptake inhibitors (sertraline), serotonin-norepinephrine reuptake inhibitors (duloxetine), rosuvastatin, and amlodipine have been reported to cause these adverse effects. This case was unique, since the patient had been on both sertraline and duloxetine previously as independent psychotropics without the development of gynecomastia. In the context of an additive drug adverse effect, the probability of sertraline as the precipitant drug was determined by both the Naranjo probability scale and the Horn drug interaction probability scale as probable. Gynecomastia is associated with antidepressants and other medications but is rarely addressed. Gynecomastia may be antidepressant selective or may be the result of additive adverse effects. Clinicians are advised to question patients regarding this potential adverse effect. Further education of clinicians is indicated.

Bleeding and Blood Disorders in Clients of Voluntary Medical Male Circumcision for HIV Prevention - Eastern and Southern Africa, 2015-2016.

PubMed

Hinkle, Lawrence E; Toledo, Carlos; Grund, Jonathan M; Byams, Vanessa R; Bock, Naomi; Ridzon, Renee; Cooney, Caroline; Njeuhmeli, Emmanuel; Thomas, Anne G; Odhiambo, Jacob; Odoyo-June, Elijah; Talam, Norah; Matchere, Faustin; Msungama, Wezi; Nyirenda, Rose; Odek, James; Come, Jotamo; Canda, Marcos; Wei, Stanley; Bere, Alfred; Bonnecwe, Collen; Choge, Isaac Ang'Ang'A; Martin, Enilda; Loykissoonlal, Dayanund; Lija, Gissenge J I; Mlanga, Erick; Simbeye, Daimon; Alamo, Stella; Kabuye, Geoffrey; Lubwama, Joseph; Wamai, Nafuna; Chituwo, Omega; Sinyangwe, George; Zulu, James Exnobert; Ajayi, Charles A; Balachandra, Shirish; Mandisarisa, John; Xaba, Sinokuthemba; Davis, Stephanie M

2018-03-23

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

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

PubMed

Claude, N

2007-09-01

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

A clinimetric approach to assessing quality of life in epilepsy.

PubMed

Cramer, J A

1993-01-01

Clinimetrics is a concept involving the use of rating scales for clinical phenomena ranging from physical examinations to functional performance. Clinimetric or rating scales can be used for defining patient status and changes that occur during long-term observation. The scores derived from such scales can be used as guidelines for intervention, treatment, or prediction of outcome. In epilepsy, clinimetric scales have been developed for assessing seizure frequency, seizure severity, adverse effects related to antiepileptic drugs (AEDs), and quality of life after surgery for epilepsy. The VA Epilepsy Cooperative Study seizure rating scale combines frequency and severity in a weighted scoring system for simple and complex partial and generalized tonic-clonic seizures, summing all items in a total seizure score. Similarly, the rating scales for systemic toxicity and neurotoxicity use scores weighted for severity for assessing specific adverse effects typically related to AEDs. A composite score, obtained by adding the scores for seizures, systemic toxicity, and neurotoxicity, represents the overall status of the patient at a given time. The Chalfont Seizure Severity Scale also applies scores relative to the impact of a given item on the patient, without factoring in seizure frequency. The Liverpool Seizure Severity Scale is a patient questionnaire covering perceived seizure severity and the impact of ictal and postictal events. The UCLA Epilepsy Surgery Inventory (ESI-55) assesses quality of life for patients who have undergone surgery for epilepsy using generic health status instruments with additional epilepsy-specific items.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

Lack of Response in an Autistic Population to a Low Dose Clinical Trial of Pyridoxine Plus Magnesium.

ERIC Educational Resources Information Center

Tolbert, Lelland; And Others

1993-01-01

As some therapeutic benefits for autistic persons have been reported from combined high doses of pyridoxine and magnesium, this study evaluated long-term administration of low doses (to minimize adverse effects) to 15 subjects with autism. Findings indicated that, at this dosage level, pyridoxine and magnesium had no effect on the severity of…

Airport noise

NASA Technical Reports Server (NTRS)

Pendley, R. E.

1982-01-01

The problem of airport noise at several airports and air bases is detailed. Community reactions to the noise, steps taken to reduce jet engine noise, and the effect of airport use restrictions and curfews on air transportation are discussed. The adverse effect of changes in allowable operational noise on airport safety and altenative means for reducing noise pollution are considered. Community-airport relations and public relations are discussed.

The control and prevention of seizures in children, a developmental and environmental approach

NASA Technical Reports Server (NTRS)

Lewinn, E. B.

1978-01-01

The clinical effectiveness of neurophysiological and developmental factors in controlling and preventing seizure mechanisms is detailed. It is shown that as cortical control advances with maturation, it requires increasingly severe environmental adversity to release this residual defensive reflex mechanism. Administration of anticonvulsant drugs is discouraged because of possible undesirable neuronal effects on the very young brain.

[Effects of Drugs Given During Pregnancy and Lactation on the Unborn Child and Neonate.

ERIC Educational Resources Information Center

Kelsey, Frances O.

This symposium presentation outlines the activity of the Food and Drug Administration (FDA) in regulating the use during pregnancy and lactation of drugs which affect the fetus and neonate. When presented with an unexpected adverse effect of a drug or of a class of drugs, the FDA can take several steps. These steps include ordering total removal…

Long-term therapy in COPD: any evidence of adverse effect on bone?

PubMed Central

Langhammer, Arnulf; Forsmo, Siri; Syversen, Unni

2009-01-01

Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis. PMID:19888355

Trace elements as paradigms of developmental neurotoxicants: lead, methylmercury and arsenic

PubMed Central

Grandjean, Philippe; Herz, Katherine T.

2014-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available several decades ago so that past and cumulated exposures could be easily characterized through analysis of biological samples, e.g. blood and urine. The first compelling evidence resulted from unfortunate poisoning events that allowed scrutiny of long-term outcomes of acute exposures that occurred during early development. Pursuant to this documentation, prospective studies of children's cohorts that applied sensitive neurobehavioral methods supported the notion that the brain is uniquely vulnerable to toxic damage during early development. Lead, methylmercury, and arsenic thereby serve as paradigm neurotoxicants that provide a reference for other substances that may have similar adverse effects. Less evidence is available on manganese, fluoride, and cadmium, but experience from the former trace elements suggest that, with time, adverse effects are likely to be documented at exposures previously thought to be low and safe. PMID:25175507

Trace elements as paradigms of developmental neurotoxicants: Lead, methylmercury and arsenic.

PubMed

Grandjean, Philippe; Herz, Katherine T

2015-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available several decades ago so that past and cumulated exposures could be easily characterized through analysis of biological samples, e.g. blood and urine. The first compelling evidence resulted from unfortunate poisoning events that allowed scrutiny of long-term outcomes of acute exposures that occurred during early development. Pursuant to this documentation, prospective studies of children's cohorts that applied sensitive neurobehavioral methods supported the notion that the brain is uniquely vulnerable to toxic damage during early development. Lead, methylmercury, and arsenic thereby serve as paradigm neurotoxicants that provide a reference for other substances that may have similar adverse effects. Less evidence is available on manganese, fluoride, and cadmium, but experience from the former trace elements suggest that, with time, adverse effects are likely to be documented at exposures previously thought to be low and safe. Copyright © 2014 Elsevier GmbH. All rights reserved.

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

PubMed

Werbel, Tyler; Cohen, Philip R

2018-04-03

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

Contrast media use in the operating room.

PubMed

Bickham, Peggy; Golembiewski, Julie

2010-04-01

Iodinated contrast media is frequently used in the OR, but often is not well understood by health care providers who are administering it. Although used for diagnosis rather than treatment, contrast media is classified as a drug by the FDA, and has indications, contraindications, adverse effects, drug interactions, disease interactions, and laboratory interference issues related to its use. Iodinated contrast media is classified according to osmolarity and ionicity, and these characteristics contribute to potential for adverse effects and choice of agent. Financial and safety concerns are factors to be considered when selecting an appropriate agent. Adverse effects can range from mild and self-limited to severe and life threatening; potentially the most serious of these are anaphylactoid reactions and contrast-induced acute renal failure. Knowledge of risk factors and preventive strategies is vital, as are issues related to substitution of gadolinium-based contrast, an off-label use. It is important for the perianesthesia nurse to become familiar with these commonly used imaging medications. Copyright 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Marginal Iodide Deficiency and Thyroid Function: Dose-response analysis for quantitative pharmacokinetic modeling

EPA Science Inventory

Severe iodine deficiency is known to cause adverse health outcomes and remains a benchmark for understanding the effects of hypothyroidism. However, the implications of marginal iodine deficiency on function of the thyroid axis remain less well known. The current study examined t...

CHEMICALS THAT DISRUPT THE THYROID AXIS: COLLABORATION BETWEEN ORD AND STAR GRANT RECIPIENTS.

EPA Science Inventory

For effective regulation, the EPA must determine the potential adverse consequences of mild disturbances of the thyroid axis on brain development. Severe hypothyroidism has long been known to lead to profound alterations in brain development and mental retardation. However, the s...

Does Steroid Abuse Cause--Or Excuse--Violence?

ERIC Educational Resources Information Center

Lubell, Adele

1989-01-01

Use of anabolic steroids is believed to increase the odds of violent antisocial behavior, thus posing risks to consumers and the general public. Some research shows the danger of steroids in inducing severe adverse psychiatric effects. Certain lawyers use this abuse to plead insanity for their clients. (SM)

Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.

PubMed

Wallace, Harriet E; Isitt, Catherine E; Broomhall, Harriet M; Perry, Alison E; Wilson, Janet D

2016-10-01

Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes. © The Author(s) 2016.

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

PubMed

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

2017-03-21

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

Childhood Adversities Associated with Poor Adult Mental Health Outcomes in Older Homeless Adults: Results From the HOPE HOME Study.

PubMed

Lee, Chuan Mei; Mangurian, Christina; Tieu, Lina; Ponath, Claudia; Guzman, David; Kushel, Margot

2017-02-01

To examine whether childhood adversity is associated with depressive symptoms, suicide attempts, or psychiatric hospitalization. History of seven childhood adversities (physical neglect, verbal abuse, physical abuse, sexual abuse, parental death, parental incarceration, and child welfare system placement) was gathered through in-person interviews. Multivariate models examined associations between history of childhood adversities and moderate to severe depressive symptoms, lifetime history of suicide attempt, or lifetime history of psychiatric hospitalization. The study enrolled 350 homeless adults, aged 50 and older, in Oakland, California, using population-based sampling methods. Moderate to severe depressive symptoms were measured on a Center for Epidemiologic Studies-Depression Scale (≥22), self-reported lifetime history of suicide attempt, and self-reported lifetime history of psychiatric hospitalization. Participants with exposure to one childhood adversity had elevated odds of reporting moderate to severe depressive symptoms (adjusted odds ratio [AOR]: 2.0; 95% confidence interval [CI]: 1.1-3.7) and lifetime history of suicide attempt (AOR: 4.6; 95% CI: 1.0-21.6) when compared with those who had none; the odds of these two outcomes increased with exposure to additional childhood adversities. Participants with four or more childhood adversities had higher odds of having a lifetime history of psychiatric hospitalization (AOR: 7.1; 95% CI: 2.8-18.0); no increase with fewer adversities was found. Childhood adversities are associated with poor mental health outcomes among older homeless adults. Clinicians should collect information about childhood adversities among this high-risk population to inform risk assessment and treatment recommendations. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Validating new summary indices for the Childhood Trauma Interview: associations with first onsets of major depressive disorder and anxiety disorders.

PubMed

Vrshek-Schallhorn, Suzanne; Wolitzky-Taylor, Kate; Doane, Leah D; Epstein, Alyssa; Sumner, Jennifer A; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Isaia, Ashley; Hammen, Constance; Adam, Emma K

2014-09-01

Childhood and adolescent adversity is of great interest in relation to risk for psychopathology, and interview measures of adversity are thought to be more reliable and valid than their questionnaire counterparts. One interview measure, the Childhood Trauma Interview (CTI; Fink et al., 1995), has been positively evaluated relative to similar measures, but there are some psychometric limitations to an existing scoring approach that limit the full potential of this measure. We propose several new summary indices for the CTI that permit examination of different types of adversity and different developmental periods. Our approach creates several summary indices: one sums the severity scores of adversities endorsed; another utilizes the number of minor and major (moderate to severe) adversities. The new indices were examined in association with first onsets of major depressive disorder (MDD) and anxiety disorders across a 5-year period using annual clinical diagnostic interviews (Structured Clinical Interview for DSM-IV-TR). Summary scores derived with the previously used approach were also examined for comparison. Data on 332 participants came from the Youth Emotion Project, a longitudinal study of risk for emotional disorders. Results support the predictive validity of the proposed summary scoring methods and indicate that several forms of major (but typically not minor) adversity are significantly associated with first onsets of MDD and anxiety disorders. Finally, multivariate regression models show that, in many instances, the new indices contributed significant unique variance predicting disorder onsets over and above the previously used summary indices. PsycINFO Database Record (c) 2014 APA, all rights reserved.

[Trimigren in stopping migraine attacks: an open prospective multicenter comparative study of rectal suppository and tablet forms of sumatriptan].

PubMed

Azimova, Iu E; Tabeeva, G R

2009-01-01

Efficacy and safety of sumatriptan in rectal suppository (50 mg) and tablet forms (50 mg) in stopping migraine attacks has been studied in 80 patients with migraine with or without aura. Dynamics of migraine pain intensity measured with the VAS 30 min, 1, 2, 6 and 24 h after the first dose of drug was a primary index of efficacy. Secondary indices were the VAS intensity of nausea, vomiting, photophobia, phonophobia, duration of each migraine attack, quality of life parameters of a patient during the migraine attack assessed with the 24-hour questionnaire, severity of migraine course on the MIDAS, percentage of patients with complete regression of migraine pain, at least in 2 out of 3 attacks. To assess drug safety, any adverse effects, data of instrumental methods (clinical and biochemical blood tests, clinical urine test), EKG were taken into account. Rectal suppository had the more rapid effect on headache reduction compared to tablets. Changes of intensity of concomitant symptoms (nausea, vomiting, photophobia, phonophobia) as well as other secondary indices of drug efficacy were similar in both groups. In the group treated with rectal suppository, 9 (22.5%) patients had 12 adverse effects. In the group treated with tablets, 22 adverse effects were noted in 15 (37.5%) patients. Adverse effects related to the cardio-vascular system were observed less often in the group treated with rectal suppository (6.6 and 32%, respectively, p=0,004).

Usefulness of basophil activation test for the diagnosis of IgE mediated hypersensitivity to tetanus toxoid vaccine.

PubMed

Herreros, Blanca; Méndez, Yesica; Feo-Brito, Francisco; Urra, José Miguel

2018-03-01

A great number of vaccinated patients develop specific anti-tetanus toxoid IgE, but usually do not undergo any adverse effect. Most of the allergic reactions to tetanus toxoid vaccine usually present with unspecific symptoms of local inflammation. In the presence of severe reactions, and in a special way if the vaccine is provided together with other drugs, it is difficult to establish which is the harmful drug responsible for IgE-mediated adverse reaction. A patient with an anaphylactic reaction after the administration of Toxoid Tetanic (TT) along with several drugs is described. All skin test were negative. The basophils activation test (BAT) in a clear way, identified TT as the allergen that triggered anaphylaxis. The results achieved demonstrates the usefulness of BAT to clarify patients with hypersensibility to tetanus toxoide when the clinic is severe and the vaccine has been administered together with other drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of stress responses on surgical performance and outcomes: Literature review and the development of the surgical stress effects (SSE) framework.

PubMed

Chrouser, Kristin L; Xu, Jie; Hallbeck, Susan; Weinger, Matthew B; Partin, Melissa R

2018-02-22

Surgical adverse events persist despite several decades of system-based quality improvement efforts, suggesting the need for alternative strategies. Qualitative studies suggest stress-induced negative intraoperative interpersonal dynamics might contribute to performance errors and undesirable patient outcomes. Understanding the impact of intraoperative stressors may be critical to reducing adverse events and improving outcomes. We searched MEDLINE, psycINFO, EMBASE, Business Source Premier, and CINAHL databases (1996-2016) to assess the relationship between negative (emotional and behavioral) responses to acute intraoperative stressors and provider performance or patient surgical outcomes. Drawing on theory and evidence from reviewed studies, we present the Surgical Stress Effects (SSE) framework. This illustrates how emotional and behavioral responses to stressors can influence individual surgical provider (e.g. surgeon, nurse) performance, team performance, and patient outcomes. It also demonstrates how uncompensated intraoperative threats and errors can lead to adverse events, highlighting evidence gaps for future research efforts. Published by Elsevier Inc.

Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban.

PubMed

Aslan, Abdullah N; Sari, Cenk; Baştuğ, Serdal; Sari, Sevil Ö; Akçay, Murat; Durmaz, Tahir; Bozkurt, Engin

2016-03-01

Rivaroxaban, a highly selective direct factor Xa inhibitor, is a new oral anticoagulant approved by the US Food and Drug Administration in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Because of its efficacy and once-a-day dosing, it is commonly preferred in patients with nonvalvular atrial fibrillation and intolerance to warfarin in clinical practice. However, it can result in some adverse effects such as bleeding, rashes and liver injury. Here, we described a very rare adverse reaction of rivaroxaban, jaundice due to intrahepatic cholestasis, appeared in a 71-year-old male patient after taking rivaroxaban.

Yellow fever: epidemiology and prevention.

PubMed

Barnett, Elizabeth D

2007-03-15

Yellow fever continues to occur in regions of Africa and South America, despite the availability of effective vaccines. Recently, some cases of severe neurologic disease and multiorgan system disease have been described in individuals who received yellow fever vaccine. These events have focused attention on the need to define criteria for judicious use of yellow fever vaccine and to describe the spectrum of adverse events that may be associated with yellow fever vaccine. Describing host factors that would increase risk of these events and identifying potential treatment modalities for yellow fever and yellow fever vaccine-associated adverse events are subjects of intense investigation.

Anorexia of Aging: Assessment and Management.

PubMed

Landi, Francesco; Picca, Anna; Calvani, Riccardo; Marzetti, Emanuele

2017-08-01

Older people often experience loss of appetite and/or decreased food intake that, unavoidably, impact energy metabolism and overall health status. The association of age-related nutritional deficits with several adverse outcomes has led to the recognition of a geriatric condition referred to as "anorexia of aging." Anorexia is an independent predictor of morbidity and mortality both in the community and across clinical settings. Multidimensional interventions within personalized care plans currently represent the most effective option to ensure the provision of adequate amounts of food, limit weight loss, and prevent adverse health outcomes in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

The Public Health Burden of Early Adversity

ERIC Educational Resources Information Center

Schlueter, Lisa J.; Watamura, Sarah Enos

2017-01-01

Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

The use of molindone in the treatment of psychotic and delirious patients infected with the human immunodeficiency virus. Case reports.

PubMed

Fernandez, F; Levy, J K

1993-01-01

Four patients with HIV infection and psychosis from various etiologies, refractory to standard treatments, and suffering from severe extrapyramidal symptoms (EPS), had a marked beneficial response to molindone. There was significant control of neuropsychiatric dysfunction without major adverse side effects. The results suggest that further evaluation is warranted of the use of molindone in treating severely ill, psychotic, or delirious HIV-infected patients.

Effectiveness and safety of abatacept in moderate to severe rheumatoid arthritis.

PubMed

Cortejoso-Fernández, Lucía; Romero-Jiménez, Maria Rosa; Pernía-López, María Sagrario; Montoro-Álvarez, María; Sanjurjo-Sáez, María

2012-01-01

Abatacept was approved in our hospital by the Pharmacy and Therapeutics Committee for treatment of moderate to severe rheumatoid arthritis (RA) in adult patients with inadequate response or intolerance to disease modifying antirheumatic drugs (DMARDs), including at least one anti-tumour necrosis factor (anti-TNF). The objectives of this study were to analyze compliance with our protocol and to evaluate effectiveness and safety of abatacept in our patients. We performed a descriptive longitudinal study of patients with RA treated with abatacept between August 2008 and May 2010 in our day care unit. We reviewed clinical records and recorded the following data: sex, age, weight, year of diagnosis, previous antirheumatic treatments and reasons for withdrawal of anti-TNFs, indication for abatacept, dose and date of administration, Disease Activity Score (DAS28) and adverse events. Effectiveness was evaluated using the European League Against Rheumatism (EULAR) criteria. We recruited 16 patients. Mean follow-up time was 10.4 (SD: 6.1) months. All patients had been previously treated with DMARDs, including at least one anti-TNF, and the mean dose of abatacept was 9.4 (SD: 1.4) mg/kg. During the first 6 months of treatment, 11/16 of patients experienced a decrease in their DAS28 value, but only 5/16 achieved a satisfactory response. Dyspnea was the most frequent adverse event (7/16), followed by fatigue and asthenia (6/16) and dry skin (5/16). The indication for abatacept in our hospital complied with the protocol approved by the Pharmacy and Therapeutics Committee. Only 5/16 of patients achieved a satisfactory response; however, it should be noted that these patients had moderate to severe RA that was refractory to other treatments. Adverse reactions were consistent with those described in the summary of product characteristics. Further studies with larger cohorts are needed to analyze the long-term safety and effectiveness profile in clinical practice.

Use of bedaquiline and delamanid in diabetes patients: clinical and pharmacological considerations.

PubMed

Hu, Minhui; Zheng, Chunlan; Gao, Feng

2016-01-01

Antituberculosis (anti-TB) treatment may be affected by both diabetes and hypoglycemic agents in patients with these 2 comorbidities. However, data supporting this conclusion relate only to standard anti-TB therapies. Sirturo ® (bedaquiline) and Deltyba ® (delamanid), novel drugs for multidrug-resistant tuberculosis (MDR-TB), are recommended for diabetes patients when another effective treatment regimen cannot be provided. Currently, there are no clinical data related to the use of these agents in diabetes patients. Possible alterations in the pharmacokinetics of these novel drugs induced by changes in subcutaneous adipose blood flow, gastric emptying, or nephropathy in diabetes patients, and possible drug-drug interactions with hypoglycemic agents, are of special interest, since the efficacy of bedaquiline and delamanid is concentration dependent. Moreover, it is of fundamental importance to avoid possible additive or synergistic effects of adverse drug reactions in this already vulnerable patient group. We reviewed clinical particularities related to the use of bedaquiline and delamanid in patients with type 1 and 2 diabetes mellitus (DM), as well as pharmacological aspects of the concurrent use of these agents with oral and injectable hypoglycemic agents. Bedaquiline shares liver metabolic pathways with several oral hypoglycemic agents, whereas delamanid may compete with several oral hypoglycemic agents and insulin analogs at protein-binding sites. Special concern exists regarding the use of bedaquiline and delamanid in diabetes patients aged >65 years and patients with severe renal or hepatic impairment or electrolyte disturbances. Concurrent use of bedaquiline and delamanid with insulin analogs, and other hypoglycemic agents that prolong the heart rate-corrected QT interval, such as sulfonylureas and glinides, may enhance this adverse reaction. Hepatic-related adverse reactions may develop more frequently when these drugs are combined with thiazolidinediones and acarbose. Data from Phase III and postmarketing studies are needed to elucidate the effect of DM and hypoglycemic agents on bedaquiline and delamanid effects in MDR-TB patients.

Adenosine and inflammation: what's new on the horizon?

PubMed

Antonioli, Luca; Csóka, Balázs; Fornai, Matteo; Colucci, Rocchina; Kókai, Endre; Blandizzi, Corrado; Haskó, György

2014-08-01

Adenosine contributes to the maintenance of tissue integrity by modulating the immune system. Encouraging results have emerged with adenosine receptor ligands for the management of several inflammatory conditions in preclinical and clinical settings. However, therapeutic applications of these drugs are sometimes complicated by the occurrence of serious adverse effects. The scientific community is making intensive efforts to design novel adenosine receptor ligands endowed with greater selectivity or to develop innovative compounds acting as allosteric receptor modulators. In parallel, research is focusing on novel pharmacological entities (designated as adenosine-regulating agents) that can increase, in a site- and event-specific manner, adenosine concentrations at the inflammatory site, thereby minimizing the adverse systemic effects of adenosine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Warfarin-induced Venous Limb Gangrene

PubMed Central

Grim Hostetler, Sarah; Sopkovich, Jennifer; Dean, Steven

2012-01-01

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene. PMID:23198012

Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population.

PubMed

Schneuer, Francisco J; Roberts, Christine L; Guilbert, Cyrille; Simpson, Judy M; Algert, Charles S; Khambalia, Amina Z; Tasevski, Vitomir; Ashton, Anthony W; Morris, Jonathan M; Nassar, Natasha

2014-02-01

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy have been associated with adverse pregnancy outcomes in a few studies but not in other studies. We assessed the serum 25(OH)D concentration at 10-14 wk of pregnancy and its association with adverse pregnancy outcomes and examined the predictive accuracy. In this nested case-control study, we measured serum 25(OH)D in 5109 women with singleton pregnancies who were attending first-trimester screening in New South Wales, Australia. Multivariate logistic regression was conducted to examine the association between low 25(OH)D concentrations and adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, gestational diabetes, miscarriage, and stillbirth). The predictive accuracy of models was assessed. The median (IQR) 25(OH)D concentration for the total population was 56.4 nmol/L (43.3-69.8 nmol/L). Serum 25(OH)D concentrations showed significant variation by parity, smoking, weight, season of sampling, country of birth, and socioeconomic status. After adjustment for maternal and clinical risk factors, low 25(OH)D concentrations were not associated with most adverse pregnancy outcomes. The area under the receiver operating characteristic curve (AUC) and likelihood ratio for a composite of severe adverse pregnancy outcomes of 25(OH)D concentrations <25 nmol/L were 0.51 and 1.44, respectively, and, for risk factors alone, were 0.64 and 2.87, respectively. The addition of 25(OH)D information to maternal and clinical risk factors did not improve the ability to predict severe adverse pregnancy outcomes (AUC: 0.64; likelihood ratio: 2.32; P = 0.39). Low 25(OH)D serum concentrations in the first trimester of pregnancy are not associated with adverse pregnancy outcomes and do not predict complications any better than routinely assessed clinical and maternal risk-factor information.

Individualized Dosing of Oral Oxybutynin for the Treatment of Primary Focal Hyperhidrosis in Children and Teenagers.

PubMed

Del Boz, Javier; Millán-Cayetano, José Francisco; Blázquez-Sánchez, Nuria; de Troya, Magdalena

2016-05-01

Oral anticholinergic drugs, such as oxybutynin, are often used in the treatment of hyperhidrosis, but few studies have focused on dosing strategies for children. The objective was to assess the effectiveness and safety of individualized dosing regimens of oral oxybutynin for treating primary focal hyperhidrosis (PFH) in children and teenagers. A prospective study was performed including patients who initiated treatment for hyperhidrosis between November 2011 and November 2014. Response to treatment and adverse effects were evaluated using the Hyperhidrosis Disease Severity Scale at baseline and at 3 and 12 months. Of 16 patients included in the study, 15 (93.8%) had responded to treatment at the 3-month follow-up (62.5% with excellent response). At the 12-month follow-up, the 11 patients who continued the treatment were still responding (63.6% with excellent response). Adverse effects were reported for 68.8% of the patients at 3 months and 54.5% at 12 months, with a predominance of oropharyngeal xerosis. No serious adverse effects were observed. Dose individualization of oral oxybutynin according to clinical response and tolerance observed in each patient is a useful management strategy in children and teenagers. © 2016 Wiley Periodicals, Inc.

Burns induced by cupping therapy in a burn center in northeast china.

PubMed

Jing-Chun, Zhao; Jia-Ao, Yu; Chun-Jing, Xian; Kai, Shi; Lai-Jin, Lu

2014-07-01

Cupping therapy as a curative skill has been developed and applied throughout history. Despite reports of adverse effects, this therapy is considered to be relatively safe with no systemic reviews documenting negative side effects. The aim of this study was to explore methods that avoid the adverse effects sometimes associated with this therapy. Clinical records of 14 outpatients and inpatients that visited the First Hospital of Jilin University (Changchun, China) for management of burn injuries caused by cupping therapy were retrospectively reviewed. Characteristics, history of injury, and treatment of each patient was collected and analyzed. Burn injury induced by cupping therapy was not uncommon. Most of the injuries were mild to moderate and cured by conservative methods without severe complications. The use of wet cupping was more prevalent among injured patients than dry cupping. Cupping therapy as an ancient alternative treatment is still popular with a large number of devoted practitioners. Although there is the potential for injury during the application of this therapy, this is mostly preventable. Standardized training for health care professionals and increased the awareness among the public about the proper methods to administer this therapy to avoid adverse effects is important.

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients.

PubMed

Yamamoto, Tetsuya; Hidaka, Yuji; Inaba, Masaaki; Ishimura, Eiji; Ooyama, Hiroshi; Kakuda, Hirokazu; Moriwaki, Yuji; Higami, Kenshi; Ohtawara, Akira; Hosoya, Tatsuo; Nishikawa, Hazime; Taniguchi, Atsuo; Ueda, Takanori; Yamauchi, Takahiro; Fujimori, Shin; Mineo, Ikuo; Yamanaka, Hisashi

2015-09-01

We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

The use of isotretinoin in acne

PubMed Central

2009-01-01

Systemic isotretinoin remains the most efficacious treatment for severe acne as well as many cases of more moderate disease that are unresponsive to other treatment modalities. The current chapter outlines the mechanisms behind the excellent efficacy, describes how to optimize treatment, reviews the recommended guidelines for monitoring and summarizes adverse effects. PMID:20436884

Comparison of Passive Sampling Devices for Measuring Dissolved PCBs in the Water Column of a Marine Superfund Site

EPA Science Inventory

The presence of contaminated sediments in aquatic environments results in several potential sources of ecological risk. These risks include the release of contaminants into the water column causing exposure to pelagic organisms. Possible adverse biological effects of this exposu...

Associations between Chlorophyll a and various microcystin-LR health advisory concentrations

EPA Science Inventory

Cyanobacteria harmful algal blooms (cHABs) are associated with a wide range of adverse health effects that stem mostly from the presence of cyanotoxins. To help protect against these impacts, several health advisory levels have been set for some toxins. In particular, one of the ...

Algal toxins and human health: A brief overview and notes on needed research directions

EPA Science Inventory

Marine and freshwater algae, both algae and cyanobacteria, are known to produce a wide variety of toxins that have caused severe adverse health effects in humans and other vertebrate species. There is general agreement that there is currently an increase in the incidence of hazar...

Metabolomics reveals the formation of aldehydes and iminium in gefitinib metabolism

USDA-ARS?s Scientific Manuscript database

Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is widely used for the treatment of cancers, particularly non-small cell lung cancer. However, its clinical use is limited by multiple adverse effects associated with GEF, such as liver and lung injuries, sever...

Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA.

PubMed

Khat, Dorrin Zarrin; Husain, Mansoor

2018-06-09

In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits. SGLT2i and GLP-1RA exert cardiovascular effects by targeting in both common and distinctive ways (A) several mediators of macro- and microvascular pathophysiology: namely (A1) inflammation and atherogenesis, (A2) oxidative stress-induced endothelial dysfunction, (A3) vascular smooth muscle cell reactive oxygen species (ROS) production and proliferation, and (A4) thrombosis. These agents also exhibit (B) hemodynamic effects through modulation of (B1) natriuresis/diuresis and (B2) the renin-angiotensin-aldosterone system. This review highlights that while GLP-1RA exert direct effects on vascular (endothelial and smooth muscle) cells, the effects of SGLT2i appear to include the activation of signaling pathways that prevent adverse vascular remodeling. Both SGLT2i and GLP-1RA confer hemodynamic effects that counter adverse cardiac remodeling.

Effects of hexagonal boron nitride on dry compression mixture of Avicel DG and Starch 1500.

PubMed

Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

2016-01-01

The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) on a (1:1) binary mixture of Avicel DG and Starch 1500 after using the dry granulation-slugging method and compare it with conventional lubricants, such as magnesium stearate (MGST), glyceryl behenate (COMP) and stearic acid (STAC). MGST is one of the most commonly used lubricants in the pharmaceutical industry. However, it has several adverse effects on tablet properties. In our current study, we employed various methods to eradicate the work hardening phenomenon in dry granulation, and used HBN as a new lubricant to overcome the adverse effects of other lubricants on tablet properties. HBN was found to be as effective as MGST and did not show any significant adverse effects on the crushing strength or work hardening. From the scanning electron microscope (SEM) images, it was concluded that HBN distributed better than MGST. As well as showing better distribution, HBN's effect on disintegration was the least pronounced. Semi-quantitative weight percent distribution of B and N elements in the tablets was obtained using EDS (energy dispersive spectroscopy). Based on atomic force microscope (AFM) surface roughness images, formulations prepared with 1% HBN showed better plastic character than those prepared with MGST.

Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness.

PubMed

Hamill, Jonathan; Hallak, Jaime; Dursun, Serdar M; Baker, Glen

2018-01-24

Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience. More recently it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation. To review ayahuasca's behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness. We searched Medline, in English, using the terms ayahuasca, dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications. The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects, safety and adverse effects; pharmacology; potential psychiatric uses. Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and many present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers feel that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized credible researchers to conduct comprehensive clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multivariate dependencies between difficult childhood, temperament and antisocial personality disorder in a population of French male prisoners.

PubMed

Pousset, M; Tremblay, R E; Falissard, B

2011-06-01

The aim of this study was to contribute to clarification of the relations between antisocial personality disorder (APD) and its potential risk factors in a population of 560 French male prisoners. Adverse childhood was assessed as a latent variable determined by several traumatic events. APD (MINI), character and temperament (Cloninger's model), WAIS®-III similarities subtest and psychosocial characteristics were assessed by two clinicians. The WAIS®-III subtest accounts for verbal and cognitive performance. We used a structural model to determine the weight of the different pathways between adverse childhood and APD. Study confirmed the major and direct role of adverse childhood (standardized coefficient=0.48). An intermediate effect mediated by character (considered as a global variable) and novelty-seeking was also shown, confirming previous results from the literature. This study emphasizes the role of adverse childhood in APD, suggesting the potential benefit of early intervention in the prevention of antisocial behaviours. Copyright © 2011. Published by Elsevier Masson SAS.

Somatic complications of epilepsy surgery over 25 years at a single center.

PubMed

Gooneratne, Inuka K; Mannan, Shahidul; de Tisi, Jane; Gonzalez, Juan C; McEvoy, Andrew W; Miserocchi, Anna; Diehl, Beate; Wehner, Tim; Bell, Gail S; Sander, Josemir W; Duncan, John S

2017-05-01

Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. We reviewed the prospectively maintained records of adults who underwent epilepsy surgery at our center between 1990 and 2014 to identify peri/postsurgical adverse events. These were categorized into neurological deficits and those related to surgery (e.g. wound infections). Neurological deficits were categorized as expected or unexpected and into transient (≤3 months) or persistent (>3 months), RESULTS: There were 911 procedures with no peri-operative deaths. Persistent neurological adverse events were seen following 157 (17.2%) procedures. The most common persistent expected complication was quadrantanopia after temporal lobe resections (72/764, 9.4%). Unexpected persistent neurological complications occurred in 20 procedures (2.2%) and included: quadrantanopia (6, 0.7%); hemianopia (2, 0.2%); hemi/mono-paresis/sensory loss (9, 1%); dysphasia (10, 1%); frontalis muscle weakness (2, 0.2%); and oculomotor weakness (1, 0.1%). 106 surgery related adverse events occurred in 83 procedures, with severe infections requiring bone-flap removal in 24 (2.6%) procedures and intracranial infections in 8 (0.9%). The risk of post-resective severe infection increased by 4 fold (OR 4.32, 95% CI 2.1-8.9, p<0.001) with use of subdural EEG monitoring prior to resection. In consequence, in August 2011 we introduced antibiotic coverage in all individuals undergoing intracranial monitoring. Also, after August 2011 there was greater use of Stereo-EEG (SEEG) than subdural (OR 9.0 CI 0.36-224.2, p=0.18ns). One complicated by severe infection. Other surgical complications included haematoma (0.3%), hydrocephalus (0.3%) and CSF leak (1.2%). None had permanent complications. Adverse event rates are similar to other series. Epilepsy surgery carries well defined surgical and neurological risks. The risks of somatic adverse events, in addition to neuropsychiatric and neuropsychological complications need to be made clear to individuals considering this treatment option. Copyright © 2017 Elsevier B.V. All rights reserved.

Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.

PubMed

McGowan, Mary P; Tardif, Jean-Claude; Ceska, Richard; Burgess, Lesley J; Soran, Handrean; Gouni-Berthold, Ioanna; Wagener, Gilbert; Chasan-Taber, Scott

2012-01-01

Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects. ClinicalTrials.gov NCT00794664.

[Intestinal cleaning for colonoscopy in children: effectiveness, adherence and adverse effects of schemes differentiated by age].

PubMed

Miquel, Isabel; Arancibia, María Eugenia; Alliende, Francisco; Ríos, Gloria; Rodríguez, Lorena; Lucero, Yalda; Saelzer, Eric

2017-04-01

Adequate intestinal cleanliness is crucial to achieve optimal colonoscopy performance. Several bowel preparation (BP) schemes have been proposed, but there is still no consensus as regards which is the most suitable in paediatric patients. To describe the effectiveness, adherence, and adverse effects of BP protocols differentiated by age group in paediatric patients subjected to colonoscopy. Prospective, study that included patients < 18 years subjected to colonoscopy. BP protocols differentiated by age group were indicated as follows: < 6 m (glycerine suppository); 6 m-3y 11 m (poly-ethylene-glycol (PEG 3350 without electrolytes); 4y-9y 11 m (PEG 3350 without electrolytes + bisacodyl); 10 y-18 y (PEG 3350 with electrolytes). Demographic, clinical information, adherence and adverse effects were registered. Effectiveness was determined using a validated scale (Boston modified) during colonoscopy. A total of 159 patients were included, of which 87 (55%) were males, and with a median age of 4 years (range 1 m-17 years). Seventy eight percent of patients achieved successful BP. The higher effectiveness was observed in the groups of < 6 m (96%) and 10-18 y (91%). Constipation was significantly more frequent (29%) in the 4 yo-9 yo 11 m in which lower effectiveness was observed (69%). Good adherence was observed in 87% of patients. Adverse effects were observed in a third of patients, although they were mild and did not lead to the suspension of the BP. Satisfactory results were achieved with the BP schemes used, with a successful BP being obtained in 4 out of 5 patients. Results were different between groups, which is probably related to previous bowel transit and indicated medication.

Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Heinen, Markus; Hettich, Moritz M.; Ryan, Devon P.; Schnell, Susanne; Paesler, Katharina; Ehninger, Dan

2012-01-01

Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome. PMID:22848851

The effect of ambient exposure to PM2.5 on the transfusion usage of blood components and adverse transfusion reactions in the haze weather.

PubMed

Chang, Chih-Chun; Lin, Hui-Jung; Sun, Jen-Tang; Li, Pei-Yu; Lee, Tai-Chen; Su, Ming-Jang; Yen, Tzung-Hai; Chu, Fang-Yeh

2016-10-01

Accumulating evidence has shown that ambient exposure to PM 2.5 , especially in the haze weather, increased the risk of various diseases. However, the association of air pollution status with blood transfusion utilization and the prevalence and severity of adverse transfusion reactions remain to be clarified. The data of monthly transfusion usage of blood components, adverse transfusion reactions, as well as PM 2.5 and PM 10 levels from 2013 to 2015 were obtained. During the study interval, both PM 2.5 and PM 10 levels were significantly increased in the haze weather when compared with the non-haze weather. The utilization of total blood components per patient-month in the haze weather was prone to be increased when compared with that in the non-haze weather (13.28 ± 1.66 vs. 12.33 ± 1.30, p = 0.068). The usage of RBC products per patient-month in the haze weather was significantly increased when compared with that in the non-haze weather (4.39 ± 0.39 vs. 4.07 ± 0.30, p = 0.009). There was no obvious difference between the haze and non-haze weathers for the usage of platelet and plasma products per patient-month. Besides, no definite differences of the prevalence and severity of transfusion-associated adverse reaction were observed between the haze and non-haze weathers. Our study first indicated that transfusion utilization, particularly the RBC products, was significantly increased in the haze weather when compared with that in the non-haze weather. There was no obvious association of air pollution with the prevalence and severity of adverse transfusion reactions and further research is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

PubMed

Deen, Kristyn; McMeniman, Erin

2015-03-01

Erosive genital lichen planus is a disabling, inflammatory mucocutaneous condition that can cause significant patient morbidity and loss of function. Treatment initially involves topical corticosteroids but some patients can have severe treatment-resistant courses requiring systemic immunosuppression. With potentially unfavorable adverse effect profiles and subsequent intolerance of these agents by patients, erosive lichen planus can ultimately be a challenging condition to treat effectively. We present a case of a 66-year-old woman with treatment-resistant erosive genital lichen planus who was successfully managed with mycophenolate mofetil. Although there is only weak evidence for this agent in this condition, its role in dermatology is growing due to its efficacy and advantageous adverse effect profile and should therefore be considered in patients with treatment-resistant erosive genital lichen planus. © 2015 Japanese Dermatological Association.

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

PubMed Central

Weeks, Howard R.; Tadler, Scott C.; Smith, Kelly W.; Iacob, Eli; Saccoman, Mikala; White, Andrea T.; Landvatter, Joshua D.; Chelune, Gordon J.; Suchy, Yana; Clark, Elaine; Cahalan, Michael K.; Bushnell, Lowry; Sakata, Derek; Light, Alan R.; Light, Kathleen C.

2013-01-01

Background Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. Method Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. Results Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. Conclusions Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial. PMID:23922809

Macroeconomic Analysis of Universal Coverage in the U.S.

NASA Astrophysics Data System (ADS)

Feng, Zhigang

In this paper I employ a dynamic general equilibrium model to study macroeconomic effects and welfare implications of health policies for universal coverage in the U.S. The model is calibrated to the U.S. data. Numerical simulations indicate that adopting universal coverage has several important macroeconomic effects on health expenditures, hours worked, and increases welfare by improving aggregate health status, and removing adverse selection.

Local and Systemic Effects of Unpolymerised Monomers

PubMed Central

Gosavi, Sulekha Siddharth; Gosavi, Siddharth Yuvraj; Alla, Rama Krishna

2010-01-01

Methyl methacrylate (MMA), a widely used monomer in dentistry and medicine has been reported to cause abnormalities or lesions in several organs. Experimental and clinical studies have documented that monomers may cause a wide range of adverse health effects such as irritation to skin, eyes, and mucous membranes, allergic dermatitis, stomatitis, asthma, neuropathy, disturbances of the central nervous system, liver toxicity, and fertility disturbances. PMID:22013462

Effects of forest fires and post-fire rehabilitation: a Colorado, USA case study

Treesearch

Lee H. MacDonald; Isaac J. Larsen

2009-01-01

Anthropogenic activities have increased the number of large, high-burn severity wildfires in the lower and mid-elevation coniferous forests in Colorado as well as much of the western US. Forests provide most of the water for cities and agriculture, and the increased runoff and erosion after wildfires is a major concern because of the potential adverse effects on...

Flow Microscopy Imaging Is Sensitive to Characteristics of Subvisible Particles in Peginesatide Formulations Associated With Severe Adverse Reactions.

PubMed

Daniels, Austin L; Randolph, Theodore W

2018-05-01

The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relationships are unknown. Images recorded by flow imaging microscopy reflect information about particle morphology, but flow microscopy is typically used to determine only particle size distributions, neglecting information on particle morphological features that may be immunologically relevant. We recently developed computational techniques that utilize the Kullback-Leibler divergence and multidimensional scaling to compare the morphological properties of particles in sets of flow microscopy images. In the current work, we combined these techniques with expectation maximization cluster analyses and used them to compare flow imaging microscopy data sets that had been collected by the U.S. Food and Drug Administration after severe adverse drug reactions (including 7 fatalities) were observed in patients who had been administered some lots of peginesatide formulations. Flow microscopy images of particle populations found in the peginesatide lots associated with severe adverse reactions in patients were readily distinguishable from images of particles in lots where severe adverse reactions did not occur. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia: A double-blind, randomized and placebo-controlled clinical study.

PubMed

Shi, D-D; Guo, J-J; Zhou, L; Wang, N

2018-02-01

Oral nifedipine is commonly used to treat pre-eclampsia, one of the most severe complications during pregnancy, but its clinical efficacy is less than ideal. Epigallocatechin gallate (EGCG), a natural compound from green tea, could benefit cardiovascular health especially hypertension. We investigated the clinical efficacy of EGCG, when complemented with oral nifedipine, in treating pre-eclampsia. A total of 350 pregnant women with severe pre-eclampsia were recruited and randomized to receive oral nifedipine, together with placebo (NIF+placebo) or EGCG (NIF+EGCG). The primary treatment outcome was the time needed to control blood pressure and interval time before a new hypertensive crisis, whereas the secondary treatment outcome was the number of treatment doses to effectively control blood pressure, maternal adverse effects and neonatal complications. Comparing NIF+EGCG group to NIF+placebo group, the time needed to control blood pressure was significantly shorter (NIF+EGCG 31.2±16.7 minutes, NIF+placebo 45.3±21.9 minutes; 95% CI 9.7-18.5 minutes), whereas interval time before a new hypertensive crisis was significantly prolonged (NIF+EGCG 7.2±2.9 hours, NIF+placebo 4.1±3.7 hours; 95% CI 2.3-3.9 hours), and the number of treatment dosages needed to effectively control blood pressure was also lower. Between the two treatment groups, no differences in incidence rates of maternal adverse effects or neonatal complications were observed. EGCG is both safe and effective in enhancing treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia, but formal validation is required prior to its recommendation for use outside of clinical trials. © 2017 John Wiley & Sons Ltd.

Influence of Network Model Detail on Estimated Health Effects of Drinking Water Contamination Events

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

Davis, Michael J.; Janke, Robert

Network model detail can influence the accuracy of results from analyses of water distribution systems. Some previous work has shown the limitations of skeletonized network models when considering water quality and hydraulic effects. Loss of model detail is potentially less important for aggregated effects such as the systemwide health effects associated with a contamination event, but has received limited attention. The influence of model detail on such effects is examined here by comparing results obtained for contamination events using three large network models and several skeletonized versions of the models. Loss of model detail decreases the accuracy of estimated aggregatedmore » adverse effects related to contamination events. It has the potential to have a large negative influence on the results of consequence assessments and the design of contamination warning systems. But, the adverse influence on analysis results can be minimized by restricting attention to high percentile effects (i.e., 95th percentile or higher).« less

Influence of Network Model Detail on Estimated Health Effects of Drinking Water Contamination Events

DOE PAGES

Davis, Michael J.; Janke, Robert

2015-01-01

Network model detail can influence the accuracy of results from analyses of water distribution systems. Some previous work has shown the limitations of skeletonized network models when considering water quality and hydraulic effects. Loss of model detail is potentially less important for aggregated effects such as the systemwide health effects associated with a contamination event, but has received limited attention. The influence of model detail on such effects is examined here by comparing results obtained for contamination events using three large network models and several skeletonized versions of the models. Loss of model detail decreases the accuracy of estimated aggregatedmore » adverse effects related to contamination events. It has the potential to have a large negative influence on the results of consequence assessments and the design of contamination warning systems. But, the adverse influence on analysis results can be minimized by restricting attention to high percentile effects (i.e., 95th percentile or higher).« less

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

PubMed

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

2012-12-01

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

Crotalidae polyvalent immune Fab: a guide to its use in North American crotaline envenomation.

PubMed

Keating, Gillian M; Lyseng-Williamson, Katherine A

2012-08-01

Intravenous crotalidae polyvalent immune Fab (CroFab(®)) is effective in patients with minimal, moderate or severe crotaline envenomation, halting the progression of local venom effects and ameliorating haematological and other systemic abnormalities of envenomation. Despite treatment, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab is generally well tolerated, with acute hypersensitivity reactions being the most commonly occurring adverse event.

Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review.

PubMed

Becher, Rune; Øvrevik, Johan; Schwarze, Per E; Nilsen, Steinar; Hongslo, Jan K; Bakke, Jan Vilhelm

2018-01-23

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children's bedrooms unless special needs indicate that carpets are preferable.

Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review

PubMed Central

Becher, Rune; Øvrevik, Johan; Schwarze, Per E.; Nilsen, Steinar; Hongslo, Jan K.; Bakke, Jan Vilhelm

2018-01-01

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children’s bedrooms unless special needs indicate that carpets are preferable. PMID:29360764

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study.

PubMed

Campos, Regis Albuquerque; Valle, Solange Oliveira Rodrigues; França, Alfeu Tavares; Cordeiro, Elisabete; Serpa, Faradiba Sarquis; Mello, Yara Ferreira; Malheiros, Teresinha; Toledo, Eliana; Mansour, Elie; Fusaro, Gustavo; Grumach, Anete Sevciovic

2014-01-01

Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

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

PubMed Central

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

2014-01-01

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

Impact of childhood adversity on the onset and course of subclinical psychosis symptoms--results from a 30-year prospective community study.

PubMed

Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Angst, Jules

2014-03-01

The study objective was to examine childhood adversity in association with intra-individual changes and inter-individual differences in subclinical psychosis in a representative community cohort over a 30-year period of observation. We analyzed two psychosis syndromes derived from the SCL-90-R - schizotypal signs and schizophrenia nuclear symptoms - in 335 participants. Participants were repeatedly assessed between 1978 (around age 20) and 2008 (around age 50). We focused specifically on inter-individual differences and intra-individual changes over time by applying structural equation modeling, generalized linear models, and generalized estimating equations. Several weak inter-individual differences revealed that increased schizotypal signs are related to various childhood adversities, such as being repeatedly involved in fights and parents having severe conflicts among themselves. We also found a significant positive association between schizotypal signs and the total number of adversities a subject experienced. This pointed toward a modest dose-response relationship. The intra-individual change in schizotypal signs over time was rather weak, although some adjustment did occur. In contrast, inter-individual schizophrenia nuclear symptoms were mainly unrelated to childhood adversity. However, some striking intra-individual changes in distress were noted over time, especially those linked with severe punishment and the total adversity score. In conclusion, we have confirmed previous positive findings about the association between childhood adversity and subsequent subclinical psychosis symptoms: An increase in adversity is weakly related to an increase of the psychosis symptom load. However, depending on the kind of adversity experienced the psychosis symptom load decreases gradually in adult life. Copyright © 2014 Elsevier B.V. All rights reserved.

Are High-Severity Fires Burning at Much Higher Rates Recently than Historically in Dry-Forest Landscapes of the Western USA?

PubMed Central

Baker, William L.

2015-01-01

Dry forests at low elevations in temperate-zone mountains are commonly hypothesized to be at risk of exceptional rates of severe fire from climatic change and land-use effects. Their setting is fire-prone, they have been altered by land-uses, and fire severity may be increasing. However, where fires were excluded, increased fire could also be hypothesized as restorative of historical fire. These competing hypotheses are not well tested, as reference data prior to widespread land-use expansion were insufficient. Moreover, fire-climate projections were lacking for these forests. Here, I used new reference data and records of high-severity fire from 1984–2012 across all dry forests (25.5 million ha) of the western USA to test these hypotheses. I also approximated projected effects of climatic change on high-severity fire in dry forests by applying existing projections. This analysis showed the rate of recent high-severity fire in dry forests is within the range of historical rates, or is too low, overall across dry forests and individually in 42 of 43 analysis regions. Significant upward trends were lacking overall from 1984–2012 for area burned and fraction burned at high severity. Upward trends in area burned at high severity were found in only 4 of 43 analysis regions. Projections for A.D. 2046–2065 showed high-severity fire would generally be still operating at, or have been restored to historical rates, although high projections suggest high-severity fire rotations that are too short could ensue in 6 of 43 regions. Programs to generally reduce fire severity in dry forests are not supported and have significant adverse ecological impacts, including reducing habitat for native species dependent on early-successional burned patches and decreasing landscape heterogeneity that confers resilience to climatic change. Some adverse ecological effects of high-severity fires are concerns. Managers and communities can improve our ability to live with high-severity fire in dry forests. PMID:26351850

Adversity in childhood linked to elevated striatal dopamine function in adulthood.

PubMed

Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

2016-10-01

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pyridostigmine for reversal of severe sequelae from botulinum toxin injection.

PubMed

Young, David L; Halstead, Lucinda A

2014-11-01

Botulinum toxin is used to treat a wide range of dystonias in the head and neck. Occasionally, patients receiving laryngeal botulinum toxin experience severe dysphagia, dyspnea, or even distant and autonomic symptoms. Rarely, these patients may require hospitalization with possible intubation and placement of nasogastric tubes. Botulinum antitoxin is not readily available and ineffective once symptoms have progressed, so patients must wait until the toxin wears off over weeks to months. Pyridostigmine prevents the breakdown of acetylcholine at the neuromuscular junction, thus making more neurotransmitter available for the muscles. A retrospective case study of patients receiving botulinum toxin for dystonia in the head and neck from 1998 to 2012 who experienced adverse effects that were successfully treated with pyridostigmine. Twenty cases were selected and reviewed to demonstrate how pyridostigmine was used to modulate severe dysphagia, breathiness, dyspnea, and some distant/autonomic symptoms. Pyridostigmine was well tolerated and resulted in significant symptom improvement. Only one significant adverse effect, bradycardia, occurred in a patient with severe cardiac disease. Given the safety and efficacy of this medication, pyridostigmine should be considered to modulate severe sequelae of botulinum toxin in select patients when conservative management is deemed insufficient. Also, physicians should be aware that patient complaints of symptoms at distant sites and temporally delayed from the injection may be a result of the botulinum toxin and relieved with pyridostigmine. Copyright © 2014 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Age-related macular degeneration: economic burden and value-based medicine analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2005-06-01

It can be estimated that 17,100 new cases of neovascular (wet) AMD and 180,000 new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition to having a devastating effect on patients' lives, the condition causes significant adverse consequences for the economy. The deleterious effect of AMD on quality of life is markedly underestimated by ophthalmologists who treat patients with AMD, by non-ophthalmic physicians and by the public. In fact, patients with different degrees of severity of AMD have a perceived impairment of their quality of life that is 96% to 750% greater than the impairment estimated by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of life of the average patient, a decrease similar to that encountered with symptomatic human immunodeficiency virus infection or moderate cardiac angina. Moderate AMD produces a 40% decrease in quality of life, a decrease similar to that associated with permanent renal dialysis or severe cardiac angina. Very severe AMD causes a 63% decrement in quality of life, a decrease similar to that encountered with advanced prostatic cancer with uncontrollable pain or a severe stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The adverse economic consequences of AMD include an annual $2.6 billion negative impact on Canada's gross domestic product. The return on investment is high for both current AMD therapies and research into new treatment modalities.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

PubMed

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The Human Experience With Ghrelin Administration

PubMed Central

Garin, Margaret C.; Burns, Carrie M.; Kaul, Shailja

2013-01-01

Context: Ghrelin is an endogenous stimulator of GH and is implicated in a number of physiological processes. Clinical trials have been performed in a variety of patient populations, but there is no comprehensive review of the beneficial and adverse consequences of ghrelin administration to humans. Evidence Acquisition: PubMed was utilized, and the reference list of each article was screened. We included 121 published articles in which ghrelin was administered to humans. Evidence Synthesis: Ghrelin has been administered as an infusion or a bolus in a variety of doses to 1850 study participants, including healthy participants and patients with obesity, prior gastrectomy, cancer, pituitary disease, diabetes mellitus, eating disorders, and other conditions. There is strong evidence that ghrelin stimulates appetite and increases circulating GH, ACTH, cortisol, prolactin, and glucose across varied patient populations. There is a paucity of evidence regarding the effects of ghrelin on LH, FSH, TSH, insulin, lipolysis, body composition, cardiac function, pulmonary function, the vasculature, and sleep. Adverse effects occurred in 20% of participants, with a predominance of flushing and gastric rumbles and a mild degree of severity. The few serious adverse events occurred in patients with advanced illness and were not clearly attributable to ghrelin. Route of administration may affect the pattern of adverse effects. Conclusions: Existing literature supports the short-term safety of ghrelin administration and its efficacy as an appetite stimulant in diverse patient populations. There is some evidence to suggest that ghrelin has wider ranging therapeutic effects, although these areas require further investigation. PMID:23533240

Management of normal tissue toxicity associated with chemoradiation (primary skin, esophagus, and lung).

PubMed

Yazbeck, Victor Y; Villaruz, Liza; Haley, Marsha; Socinski, Mark A

2013-01-01

Nearly one quarter of patients with lung cancer present with locally advanced disease where concurrent chemoradiotherapy is the current standard of care for patients with good performance status. Cisplatin-based concurrent chemoradiotherapy consistently showed an improvement in survival compared with sequential chemoradiotherapy, at the expense of an increase in the toxicity profile. Over the past decades, several encouraging biomarkers such as transforming growth factor-beta and radioprotective agents such as amifostine were studied but without reaching approval for patient care. We reviewed the prevalence and risk factors for different adverse effects associated with the combined chemoradiotherapy modality, especially dermatitis, mucositis, esophagitis, and pneumonitis. These adverse effects can further be divided into acute, subacute, and chronic. Dermatitis is usually rare and responds well to topical steroids and usual skin care. Acute esophagitis occurs in 30% of patients and is treated with proton pump inhibitors, promotility agents, local anesthetic, and dietary changes. Radiation pneumonitis is a subacute complication seen in 15% of patients and is usually managed with steroids. Chronic adverse effects such as radiation fibrosis and esophageal stricture occur approximately 6 months after completion of radiation therapy and are usually permanent. In this review, complications of chemoradiotherapy for patients with locally advanced lung cancer are delineated, and approaches to their management are described. Given that treatment interruption is associated with a worse outcome, patients are aggressively treated with a curative intent. Therefore, planning for treatment adverse effects improves patient tolerance, compliance, and outcome.

MERIS (Medical Error Reporting Information System) as an innovative patient safety intervention: a health policy perspective.

PubMed

Riga, Marina; Vozikis, Athanassios; Pollalis, Yannis; Souliotis, Kyriakos

2015-04-01

The economic crisis in Greece poses the necessity to resolve problems concerning both the spiralling cost and the quality assurance in the health system. The detection and the analysis of patient adverse events and medical errors are considered crucial elements of this course. The implementation of MERIS embodies a mandatory module, which adopts the trigger tool methodology for measuring adverse events and medical errors an intensive care unit [ICU] environment, and a voluntary one with web-based public reporting methodology. A pilot implementation of MERIS running in a public hospital identified 35 adverse events, with approx. 12 additional hospital days and an extra healthcare cost of €12,000 per adverse event or of about €312,000 per annum for ICU costs only. At the same time, the voluntary module unveiled 510 reports on adverse events submitted by citizens or patients. MERIS has been evaluated as a comprehensive and effective system; it succeeded in detecting the main factors that cause adverse events and discloses severe omissions of the Greek health system. MERIS may be incorporated and run efficiently nationally, adapted to the needs and peculiarities of each hospital or clinic. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31).

PubMed

Tax, W J; Tamboer, W P; Jacobs, C W; Frenken, L A; Koene, R A

1997-01-15

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration ("first-dose reaction"). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this Fc gammaRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-alpha in all four HR patients and none of the five LR patients. In all HR patients except one, plasma gamma-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+ cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-alpha by itself is not sufficient to induce the first-dose reaction.

RotaTeq vaccine adverse events and policy considerations.

PubMed

Geier, David A; King, Paul G; Sykes, Lisa K; Geier, Mark R

2008-03-01

Rotavirus is the leading cause of severe gastroenteritis in children <5 years-old worldwide. On February 3, 2006, the US Food and Drug Administration licensed RotaTeq (Merck and Co.), a bioengineered combination of five human-bovine hybridized reassortment rotaviruses. In August of 2006, the Advisory Committee on Immunization Practices recommended RotaTeq for routine vaccination of US infants administered orally at the ages 2, 4, and 6 months. An evaluation of data reported to VAERS following the first five quarters of post-marketing surveillance of RotaTeq was undertaken. Trends in adverse events reported following RotaTeq and cost-effectiveness calculations of RotaTeq in the context of the disease burden of rotavirus in the US were examined. From February 3, 2006 through July 31, 2007, a total of 160 (of the 165 reported) intussusception and 11 (of the 16 reported) Kawasaki disease adverse event reports were identified when RotaTeq was administered or co-administered with other vaccines. Time-trend analyses showed that there were significant increases in the total number of intussusception and Kawasaki disease adverse events entered into VAERS in comparison to previous years. These observations, coupled with limited rotavirus disease burden, cost-effectiveness, and potential contact viral transmission concerns, raise serious questions regarding the use of RotaTeq in the US. Healthcare providers should diligently report adverse events following RotaTeq vaccination to VAERS, and those who have experienced a vaccine-associated adverse event should be made aware that they may be eligible for compensation from the no-fault National Vaccine Injury Compensation Program (NVICP).

Prevalence, Type, Disclosure, and Severity of Adverse Life Events in College Students

ERIC Educational Resources Information Center

Smyth, Joshua M.; Hockemeyer, Jill R.; Heron, Kristin E.; Wonderlich, Stephen A.; Pennebaker, James W.

2008-01-01

Objective: Some information on the prevalence of adverse life experiences is available for the general population and college students, but the extent, nature, and severity of these events is unclear. Participants: The authors recruited undergraduate college students (N = 6,053) from diverse academic settings (public and private schools) and…

Silage review: Mycotoxins in silage: Occurrence, effects, prevention, and mitigation.

PubMed

Ogunade, I M; Martinez-Tuppia, C; Queiroz, O C M; Jiang, Y; Drouin, P; Wu, F; Vyas, D; Adesogan, A T

2018-05-01

Ensiled forage, particularly corn silage, is an important component of dairy cow diets worldwide. Forages can be contaminated with several mycotoxins in the field pre-harvest, during storage, or after ensiling during feed-out. Exposure to dietary mycotoxins adversely affects the performance and health of livestock and can compromise human health. Several studies and surveys indicate that ruminants are often exposed to mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins, zearalenone, and many other fungal secondary metabolites, via the silage they ingest. Problems associated with mycotoxins in silage can be minimized by preventing fungal growth before and after ensiling. Proper silage management is essential to reduce mycotoxin contamination of dairy cow feeds, and certain mold-inhibiting chemical additives or microbial inoculants can also reduce the contamination levels. Several sequestering agents also can be added to diets to reduce mycotoxin levels, but their efficacy varies with the type and level of mycotoxin contamination. This article gives an overview of the types, prevalence, and levels of mycotoxin contamination in ensiled forages in different countries, and describes their adverse effects on health of ruminants, and effective prevention and mitigation strategies for dairy cow diets. Future research priorities discussed include research efforts to develop silage additives or rumen microbial innocula that degrade mycotoxins. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Analysis of Acute Transfusion Reactions and Their Occurrence Times

PubMed Central

Hatayama, Yuki; Matsumoto, Satoko; Hamada, Eiko; Kojima, Nao; Hara, Ayako; Hino, Norihiko; Motokura, Toru

2018-01-01

Acute transfusion reactions (ATRs) are significantly relevant to the morbidity and mortality of patients. ATRs are mostly not severe and rarely cause severe conditions, including anaphylactic shock. The aim of this study was to clarify the frequency of ATRs and the time of event occurrence. A total of 18,745 transfusions were administered to 11,718 patients during a 3-year period. Adverse reactions including at least one sign or symptom were collected through a report system in 143 of 2,478 (5.7%) platelet concentrate transfusions, 105 of 6,629 (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse events. Severe signs and symptoms were observed in 7.1% of patients. These events appeared significantly earlier than those of non-severe signs and symptoms (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive transfusion-associated adverse events, preventive treatments for adverse events should be proactively promoted. PMID:29599628

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

PubMed

Geneen, Louise J; Moore, R Andrew; Clarke, Clare; Martin, Denis; Colvin, Lesley A; Smith, Blair H

2017-01-14

Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

PubMed

Geneen, Louise J; Moore, R Andrew; Clarke, Clare; Martin, Denis; Colvin, Lesley A; Smith, Blair H

2017-04-24

Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: an indirect treatment comparison meta-analysis.

PubMed

Thorlund, Kristian; Druyts, Eric; Mills, Edward J; Fedorak, Richard N; Marshall, John K

2014-07-01

To compare the efficacy of adalimumab and infliximab for the treatment of moderate to severe ulcerative colitis using indirect treatment comparison meta-analysis. A systematic review and Bayesian indirect treatment comparison meta-analyses were performed for seven patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrIs) were produced. Five eligible RCTs informed clinical remission, response, mucosal healing, quality of life, colectomy, serious adverse events, and discontinuation due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy, clinical remission (OR=0.42, 95% CrI 0.17-0.97), clinical response (OR=0.45, 95% CrI 0.23-0.89) and mucosal healing (OR=0.46, 95% CrI 0.25-0.86) statistically favored infliximab. However, after 52 weeks of maintenance therapy OR estimates showed no significant difference between infliximab and adalimumab. For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab were similar to placebo. Further, the indirect treatment comparison of adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals. The findings of this indirect treatment comparison meta-analysis suggest that both infliximab and adalimumab are superior to placebo in the treatment of moderate to moderately severe ulcerative colitis. While infliximab is statistically more effective than adalimumab in the induction of remission, response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable in efficacy at 52 weeks of maintenance treatment. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

A double blind, randomized, placebo controlled trial of the efficacy, quality of life and safety of food allergen-specific sublingual immunotherapy in client owned dogs with adverse food reactions: a small pilot study.

PubMed

Maina, Elisa; Cox, Eric

2016-10-01

Food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a novel and successful approach for desensitizing human patients to specific food allergens. It has not been tested in dogs. To investigate the efficacy, quality of life (QoL), tolerability and safety of FA-SLIT in dogs with adverse food reactions (AFR). Dogs with proven AFR were randomized to treatment (T group; n = 7) or placebo (P group; n = 6) to receive either FA-SLIT (based on the results of a food elimination trial) or glycerinated saline, respectively. The treatment was continued daily for 6 months with fortnightly dosage escalations. To evaluate the treatment, pruritus Visual Analog Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), QoL, faecal consistency scores, owner assessment, overall tolerability scores and blood analyses were assessed. Eleven dogs completed the study, two dogs in the T group were withdrawn by the owner after FA-SLIT exacerbated clinical signs of AFR. Statistical tests showed significant protection against food challenge induced clinical signs following FA-SLIT therapy, as indicated by reduced pVAS and CADESI scores (P < 0.05). The QoL did not differ between groups. The treatment was rated as effective or quite effective by 80% of the owners, whereas placebo was rated as ineffective by all owners. FA-SLIT was effective, well tolerated and safe. No severe adverse events were recorded; erythema and pruritus were reported in association with only 0.7% of the dispensed doses. Larger clinical trials with more extended maintenance immunotherapy periods will be needed to provide more precise estimates of efficacy and frequency of adverse events. © 2016 ESVD and ACVD.

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study.

PubMed

Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M; Thornton, Laura M; Koch, Susanne Vinkel; Mortensen, Preben Bo; Petersen, Liselotte

2017-12-01

Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women. In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression. Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively. Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN. © 2017 Wiley Periodicals, Inc.

Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases

PubMed Central

Zhong, Yifei; Deng, Yueyi; Chen, Yiping; Chuang, Peter Y; He, John Cijiang

2013-01-01

Traditional Chinese herbal medications (TCHM) are frequently used in conjunction with western pharmacotherapy for treatment of chronic kidney diseases (CKD) in China and many other Asian countries. The practice of traditional Chinese medicine is guided by cumulative empiric experience. Recent in vitro and animal studies have confirmed the biological activity and therapeutic effects of several TCHM in CKD. However, the level of evidence supporting TCHM is limited to small, non-randomized trials. Due to variations in the prescription pattern of TCHM and the need for frequent dosage adjustment, which are inherent to the practice of traditional Chinese medicine, it has been challenging to design and implement large randomized clinical trials of TCHM. Several TCHM are associated with significant adverse effects, including nephrotoxicity. However, reporting of adverse effects associated with TCHM has been inadequate. To fully realize the therapeutic use of TCHM in CKD we need molecular studies to identify active ingredients of TCHM and their mechanism of action, rigorous pharmacologic studies to determine the safety and meet regulatory standards required for clinical therapeutic agents, and well-designed clinical trials to provide evidence-based support of their safety and efficacy. PMID:23868014

RISK COMMUNICATION FOR ES&H PROFESSIONALS AND LINE SUPERVISORS PARTICIPANT MANUAL COURSE NUMBER 004111 REV 0.1 JULY 2011

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

ALDRIDGE PK; ROCKS S

This course will help you successfully apply risk communication principles when interacting with workers regarding work hazards. What Is the Difference Between a Risk and a Hazard? In many cases, the terms 'risk' and 'hazard' are incorrectly used interchangeably. A hazard is a physical condition or practice with the potential for causing harm/adverse effects. A risk is the probability of harm/adverse effects occurring from an exposure to a hazard. It is modified by the severity of harm (the consequence). Once a hazard is identified, a risk assessment is conducted to determine the severity of the risk. It uses scientific methodsmore » and rigorous tests to determine the effects of the risk on people and the environment. Risk Management takes data from the risk assessment and writes policies to help protect people and the environment against the risk. Risk communication is an ongoing process that starts soon after a hazard is identified and continues through the writing of policies. In the past, governing agencies did not do a good job of communicating risk; they would only communicate about risk after studies had been conducted and policies written.« less

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

PubMed

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

PubMed Central

Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz

2011-01-01

Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

Drug safety evaluation of naltrexone/bupropion for the treatment of obesity.

PubMed

Verpeut, Jessica L; Bello, Nicholas T

2014-06-01

Obesity is a known health risk for the development of several preventable diseases. Obesity-related metabolic alterations negatively impact different physiological mechanisms, which supports the rationale for the use of combined drug therapy. Naltrexone is an opioid antagonist for the treatment of opioid and alcohol dependency, whereas bupropion is a norepinephrine/dopamine reuptake inhibitor used to treat depression and smoking cessation. Although not effective as individual monotherapies for obesity, naltrexone and bupropion in combination produce weight loss and a metabolic profile beneficial for the potential treatment of obesity. This review examines the safety and antiobesity effects of naltrexone and bupropion alone and in combination. It reviews the results of four Phase III clinical trials of a novel fixed dose of sustained-released naltrexone/bupropion. Naltrexone/bupropion has a greater weight loss efficacy than two FDA-approved medications, orlistat and lorcaserin. Although the weight loss produced by phentermine/topiramate is superior to naltrexone/bupropion, the safety profile of naltrexone/bupropion has less severe adverse effects. In addition, naltrexone/bupropion is well tolerated, with nausea being the most reported adverse event. Unlike other centrally acting medications, lorcaserin and phentermine/topiramate, naltrexone/bupropion has no abuse potential.

Social Environmental Variation, Plasticity Genes, and Aggression: Evidence for the Differential Susceptibility Hypothesis

PubMed Central

Simons, Ronald L.; Lei, Man Kit; Beach, Steven R.H.; Brody, Gene H.; Philibert, Robert A.; Gibbons, Frederick X.

2011-01-01

Although G×E studies are typically based on the assumption that some individuals possess genetic variants that enhance their vulnerability to environmental adversity, the differential susceptibility perspective posits that these individuals are simply more susceptible to environmental influence than others. An important implication of this model is that those persons most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. The present study tested several implications of this proposition. Using longitudinal data from a sample of several hundred African Americans, we found that relatively common variants of the dopamine receptor gene and the serotonin transporter gene interact with social environmental conditions to predict aggression in a manner consonant with differential susceptibility. When the social environment was adverse, individuals with these genetic variants manifested more aggression than other genotypes, whereas when the environment was supportive they demonstrated less aggression than other genotypes. Further, we found that these genetic variants interact with environmental conditions to foster various cognitive schemas and emotions in a manner consistent with differential susceptibility and that a latent construct formed by these schemas and emotions mediated the effect of gene by environment interaction on aggression. PMID:22199399

A case of probable labetalol induced hyperkalaemia in pre-eclampsia.

PubMed

Thomas, Binny; Abdul Rouf, P V; El Kassem, Wessam; Al Hail, Moza; Stewart, Derek; Tharannum, Asma; Ahmed, Afif; Al Saadi, Muna

2014-12-01

Hyperkalemia can cause altered cardiac electrical conduction resulting in death. We describe a case of a 23-year old pregnant patient who presented with severe epigastric pain and vomiting. She was severely pre- eclamptic and received initial treatment with intravenous labetalol and decision was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4 mmol/L) and labetalol was discontinued and intravenous hydralazine commenced. Post-surgery, her potassium levels were normal but due to rapidly rising blood pressure labetalol was recommenced, resulting in elevated potassium levels. Labetolol was discontinued, hydralazine prescribed, and potassium levels normalised. The adverse reaction was classified as 'probably' due to labetolol using the Naranjo Adverse Drug Reaction scale. This is the first reported case of labetolol induced hyperkalaemia in pregnancy, with life threatening consequences and hence all health professionals should be alert to this potential effect.

RETROSPECTIVE EVALUATION OF A NOVEL SUSTAINED-RELEASE IVERMECTIN VARNISH FOR TREATMENT OF WOUND MYIASIS IN ZOO-HOUSED ANIMALS.

PubMed

Avni-Magen, Nili; Eshar, David; Friedman, Michael; Kirmayer, David; Letschert, Lital; Gati, Irith; Kaufman, Elizabeth; Paz, Avital; Lavy, Eran

2018-03-01

Myiasis is a major disease condition in human and veterinary medicine. Domestic, free-ranging, and zoo-housed animals can be severely affected by myiasis. Depending on case severity, multiple treatment episodes may be indicated and can lead to recurrent capturing, handling stress, and anesthetics, all of which increase the risk of adverse responses (including death) individually and also in the herd. As an insecticide, ivermectin is often used for larval control. A total of 28 individual myiasis cases were retrospectively evaluated, out of which 11 cases were also treated using an ivermectin sustained-release varnish (SRV). The clinical outcome of all cases was assessed and the results suggest that the use of a topical ivermectin SRV (with or without concurrent injectable ivermectin) can reduce handling and treatments, has no adverse effects, and has minimal recurrence of the disease when compared with cases treated without it.

Decreasing severe pain and serious adverse events while moving intensive care unit patients: a prospective interventional study (the NURSE-DO project).

PubMed

de Jong, Audrey; Molinari, Nicolas; de Lattre, Sylvie; Gniadek, Claudine; Carr, Julie; Conseil, Mathieu; Susbielles, Marie-Pierre; Jung, Boris; Jaber, Samir; Chanques, Gérald

2013-04-18

A quality-improvement project was conducted to reduce severe pain and stress-related events while moving ICU-patients. The Plan-Do-Check-Adjust cycle was studied during four one-month phases, separated by five-month interphases. All consecutive patients staying more than 24 hours were evaluated every morning while being moved for nursing care (bathing, massage, sheet-change, repositioning). Phase 1 was considered as the baseline. Implemented and adjusted quality-interventions were assessed at phases 2 and 3, respectively. An independent post-intervention control-audit was performed at Phase 4. Primary-endpoints were the incidence of severe pain defined by a behavioral pain scale > 5 or a 0 to 10 visual numeric rating scale > 6, and the incidence of serious adverse events (SAE): cardiac arrest, arrhythmias, tachycardia, bradycardia, hypertension, hypotension, desaturation, bradypnea or ventilatory distress. Pain, SAE, patients' characteristics and analgesia were compared among the phases by a multivariate mixed-effects model for repeated-measurements, adjusted on severity index, age, admission type (medical/surgical), intubation and sedation status. During the four studied phases, 630 care procedures were analyzed in 53, 47, 43 and 50 patients, respectively. Incidence of severe pain decreased significantly from 16% (baseline) to 6% in Phase 3 (odds ratio (OR) = 0.33 (0.11; 0.98), P = 0.04) and 2% in Phase 4 (OR = 0.30 (0.12; 0.95), P = 0.02). Incidence of SAE decreased significantly from 37% (baseline) to 17% in Phase 3 and 21% in Phase 4. In multivariate analysis, SAE were independently associated with Phase 3 (OR = 0.40 (0.23; 0.72), P < 0.01), Phase 4 (OR = 0.53 (0.30; 0.92), P = 0.03), intubation status (OR = 1.91 (1.28; 2.85), P < 0.01) and severe pain (OR = 2.74 (1.54; 4.89), P < 0.001). Severe pain and serious adverse events are common and strongly associated while moving ICU patients for nursing procedures. Quality improvement of pain management is associated with a decrease of serious adverse events. Careful documentation of pain management during mobilization for nursing procedures could be implemented as a health quality indicator in the ICU.

Lubiprostone Is Effective in the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Li, Fan; Fu, Tao; Tong, Wei-Dong; Liu, Bao-Hua; Li, Chun-Xue; Gao, Yu; Wu, Jin-Song; Wang, Xiang-Feng; Zhang, An-Ping

2016-04-01

To evaluate the efficacy and safety of lubiprostone in the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). We performed a literature search of the MEDLINE, Cochrane, Google Scholar, and ClinicalTrials.gov databases (from January 1, 2005, through January 31, 2015). Relevant studies meeting the inclusion criteria were manually searched by 2 independent reviewers. Efficacy outcomes evaluated at 1 week, 1 month, and 3 months of intervention were weekly frequency of spontaneous bowel movements, severity of constipation, consistency of stools, degree of abdominal pain/discomfort, degree of straining, and abdominal bloating. Of 246 studies identified, data from 9 trials comprising 1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the placebo group were analyzed. We found that lubiprostone treatment significantly improved the severity of constipation, stool consistency, abdominal pain, degree of straining, and abdominal bloating at 1 week (P≤.03) and 1 month (P≤.004), except for abdominal pain at 1 month, which was similar to that when treated with placebo (P=.21). At 3 months, except for abdominal bloating (P=.03), there was no difference between lubiprostone and placebo groups in all other outcomes (P≥.05). Adverse effects such as nausea, vomiting, and diarrhea were common (incidence rate, 2.4%-75%); however, the incidence of serious adverse effects was low (<5%) and was mostly unrelated to lubiprostone treatment. Lubiprostone is a safe and efficacious drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, with limited adverse effects in 3 months of follow-up. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Sex differences in the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I and II disorder.

PubMed

Erol, Almila; Winham, Stacey J; McElroy, Susan L; Frye, Mark A; Prieto, Miguel L; Cuellar-Barboza, Alfredo B; Fuentes, Manuel; Geske, Jennifer; Mori, Nicole; Biernacka, Joanna M; Bobo, William V

2015-09-01

To examine the independent effects of sex on the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I disorder (BP-I) or bipolar II disorder (BP-II). We analyzed data from the first 1,225 patients enrolled in the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. Demographic and clinical variables were ascertained using standardized questionnaires; height and weight were assessed to determine body mass index (BMI). Rates of rapid cycling, cycle acceleration, and increased severity of mood episodes over time were compared between women and men overall and within subgroups defined by bipolar disorder subtype (BP-I or BP-II). Multiple logistic regression analysis was used to assess the independent effect of sex on the risk of these indicators of adverse illness course. Women had significantly higher rates of rapid cycling than men. Overall rates of rapid cycling were higher in patients with BP-II than BP-I; and sex differences in the rate of rapid cycling were more pronounced in patients with BP-II than BP-I, although the power to detect statistically significant differences was reduced due to the lower sample size of subjects with BP-II. Female sex was a significant predictor of rapid cycling, cycle acceleration, and increased severity of mood episodes over time after adjusting for age, bipolar disorder subtype, BMI, having any comorbid psychiatric disorder, and current antidepressant use. Female sex was associated with significantly higher risk of rapid cycling, cycle acceleration, and increased severity of mood episodes over time in a sample of 1,225 patients with bipolar disorders. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

PubMed Central

Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

2014-01-01

Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

Parenteral opioids for maternal pain management in labour

PubMed Central

Ullman, Roz; Smith, Lesley A; Burns, Ethel; Mori, Rintaro; Dowswell, Therese

2014-01-01

Background Parenteral opioids are used for pain relief in labour in many countries throughout the world. Objectives To assess the acceptability, effectiveness and safety of different types, doses and modes of administration of parenteral opioids given to women in labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 April 2011) and reference lists of retrieved studies. Selection criteria We included randomised controlled trials examining the use of intramuscular or intravenous opioids (including patient controlled analgesia) for women in labour. We looked at studies comparing an opioid with another opioid, placebo, other non-pharmacological interventions (TENS) or inhaled analgesia. Data collection and analysis At least two review authors independently assessed study eligibility, collected data and assessed risk of bias. Main results We included 57 studies involving more than 7000 women that compared an opioid with placebo, another opioid administered intramuscularly or intravenously or compared with TENS to the back. The 57 studies reported on 29 different comparisons, and for many outcomes only one study contributed data. Overall, the evidence was of poor quality regarding the analgesic effect of opioids, satisfaction with analgesia, adverse effects and harm to women and babies. There were few statistically significant results. Many of the studies had small sample sizes, and low statistical power. Overall findings indicated that parenteral opioids provided some pain relief and moderate satisfaction with analgesia in labour, although up to two-thirds of women who received opioids reported moderate or severe pain and/or poor or moderate pain relief one or two hours after administration. Opioid drugs were associated with maternal nausea, vomiting and drowsiness, although different opioid drugs were associated with different adverse effects. There was no clear evidence of adverse effects of opioids on the newborn. We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects. Authors’ conclusions Parenteral opioids provide some relief from pain in labour but are associated with adverse effects. Maternal satisfaction with opioid analgesia was largely unreported but appeared moderate at best. This review needs to be examined alongside related Cochrane reviews examining pain management in labour. More research is needed to determine which analgesic intervention is most effective, and provides greatest satisfaction to women with acceptable adverse effects for mothers and their newborn. PMID:20824859

Electroconvulsive Therapy for Agitation and Aggression in Dementia: A Systematic Review.

PubMed

van den Berg, Julia F; Kruithof, Henk C; Kok, Rob M; Verwijk, Esmée; Spaans, Harm-Pieter

2018-04-01

Many patients with dementia develop agitation or aggression in the course of their disease. In some severe cases, behavioral, environmental, and pharmacological interventions are not sufficient to alleviate these potentially life-threatening symptoms. It has been suggested that in those cases, electroconvulsive therapy (ECT) could be an option. This review summarizes the scientific literature on ECT for agitation and aggression in dementia. We performed a systematic review in accordance with PRISMA guidelines. A search was conducted in Ovid MEDLINE, EMBASE, and PsycINFO. Two reviewers extracted the following data from the retrieved articles: number of patients and their age, gender, diagnoses, types of problem behavior, treatments tried before ECT, specifications of the ECT treatment, use of rating scales, treatment results, follow-up data, and adverse effects. The initial search yielded 264 articles, 17 of which fulfilled the inclusion criteria. Of these studies, one was a prospective cohort study, one was a case-control study, and the others were retrospective chart reviews, case series, or case reports. Clinically significant improvement was observed in the majority (88%) of the 122 patients described, often early in the treatment course. Adverse effects were most commonly mild, transient, or not reported. The reviewed articles suggest that ECT could be an effective treatment for severe and treatment-refractory agitation and aggression in dementia, with few adverse consequences. Nevertheless, because of the substantial risk of selection bias, the designs of the studies reviewed, and their small number, further prospective studies are needed to substantiate these preliminary positive results. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Similarities and differences in acute response to major ions among several aquatic species: Implications for guideline development

EPA Science Inventory

Adverse effects from increased concentrations of major geochemical ions (Na, K, Ca, Mg, Cl, SO4, HCO3) to aquatic organisms have been demonstrated or implied in many settings. However, experimental work has shown that the toxicity of ion mixtures is dependent on the specific mix...

Pruning open-grown black cherry

Treesearch

T. J. Grisez

1967-01-01

Black cherry trees that had large crown ratios and were 4 to 6 inches d. b. h. were pruned to various heights. Epicormic sprouting was severe and diameter growth at breast height was reduced on trees pruned to 75 percent of their height. Most trees pruned to 50 percent show little or no adverse effect after 3 years.

Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease.

PubMed

Sharmila, Vijayan; Babu, Thirunavukkarasu Arun

2015-01-01

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.

Comparison of fetal testosterone production in various tissues of the male sprague dawley rat dosed in utero with dipentyl phthalate during the critical window of sexual differentiation

EPA Science Inventory

Phthalate esters are high-production volume chemicals used in the manufacture of numerous plastics and consumer products, which generates major concern for potential human exposure and environmental contamination. Several studies have demonstrated adverse effects associated with ...

75 FR 2896 - Alabama Disaster Number AL-00028

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... (FEMA-1870-DR), dated 12/31/2009. Incident: Severe Storms and Flooding. Incident Period: 12/12/2009 through 12/18/2009. DATES: Effective Date: 01/08/2010. Physical Loan Application Deadline Date: 03/01/2010... the State of Alabama, dated 12/31/2009, is hereby amended to include the following areas as adversely...

75 FR 46924 - Notice of Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

... high and adverse human health impacts or environmental effects from exposure to the pesticides... regulator, trinexapac-ethyl: 4-(cyclopropyl-[alpha]-hydroxy-methylene)- 3,5-dioxo-cyclohexanecarboxylic acid...,5-dioxo-cyclohexanecarboxylic acid, in or on grass, forage, grown for seed at 1.60 ppm; grass, hay...

A Mouse Click Away: Internet Resources for Students in Crisis in Geographically Isolated or Self-Sequestered Communities

ERIC Educational Resources Information Center

Gary, Juneau Mahan

2010-01-01

The impact, incidence, prevalence, and severity of violence and trauma adversely affect students academically, behaviorally, emotionally, and socially. For students residing in geographically isolated or self-sequestered communities, trauma may be exacerbated when school counselors may be unprepared to respond effectively and timely because…

Adverse Effects of Heavy Prenatal Maternal Smoking on Attentional Control in Children with ADHD

ERIC Educational Resources Information Center

Motlagh, Maria G.; Sukhodolsky, Denis G.; Landeros-Weisenberger, Angeli; Katsovich, Liliya; Thompson, Nancy; Scahill, Lawrence; King, Robert A.; Peterson, Bradley S.; Schultz, Robert T.; Leckman, James F.

2011-01-01

Objective: Exposure to heavy maternal cigarette smoking in pregnancy and severe maternal psychosocial stress during pregnancy appear to be important risk factors for the development of ADHD. This study aimed to determine whether these perinatal risk factors were associated with neuropsychological deficits commonly seen in ADHD. Method: We examined…

The Acute Toxicity of Major Ion Salts to Ceriodaphnia Dubia. Ii. Empirical Relationships in Binary Salt Mixtures

EPA Science Inventory

Many human activities increase concentrations of major geochemical ions (Na+, K+, Ca+2, Mg+2, Cl, SO42, and HCO3/CO32) in fresh water systems, and can thereby adversely affect aquatic life. Such effects involve several toxicants, multiple mechanisms of toxicity, various ion inte...

A Literature Review of the Strengths and Limitations of Premarital Preparation: Implications for a Canadian Context

ERIC Educational Resources Information Center

Green, Amy R.; Miller, Lynn D.

2013-01-01

The adverse effects of marital dissolution and dissatisfaction point to a need for interventions, such as premarital preparation, to improve marital quality. Although several studies support the potential for premarital preparation to improve couples' marital satisfaction and interpersonal skills, results from other studies are mixed. Moreover,…

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Failure or success of search strategies to identify adverse effects of medical devices: a feasibility study using a systematic review.

PubMed

Golder, Su; Wright, Kath; Rodgers, Mark

2014-10-13

Research has indicated that adverse effects terms are increasingly prevalent in the title, abstract or indexing terms of articles that contain adverse drug effects data in MEDLINE and Embase. However, it is unknown whether adverse effects terms are present in the database records of articles that contain adverse effects data of medical devices, and thus, to what extent the development of an adverse effects search filter for medical devices may be feasible. A case study systematic review of a medical device was selected. The included studies from a systematic review of the safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) for spinal fusion were used in the analysis. For each included study, the corresponding database record on MEDLINE and Embase was assessed to measure the presence or absence of adverse effects terms in the title, abstract or indexing. The performance of each potential adverse effects search term was also measured and compared. There were 82 publications (49 studies) included in the systematic review with 51 of these indexed on MEDLINE and 55 on Embase. Ninety-four percent (48/51) of the records on MEDLINE and 95% (52/55) of the records on Embase contained at least one adverse effects related search term. The wide variety of adverse effects terms included in the title, abstract or indexing of bibliographic records, and the lack of any individual high-performing search terms suggests that a combination of terms in different fields is required to identify adverse effects of medical devices. In addition, the most successful search terms differed from the most successful terms for identifying adverse drug effects. The search filters currently available for adverse drug effects are not necessarily useful for searching adverse effects data of medical devices. The presence of adverse effects terms in the bibliographic records of articles on medical devices, however, indicates that combinations of adverse effects search terms may be useful in search strategies in MEDLINE and Embase. The results, therefore, suggest that not only a search filter for the adverse effects of medical devices is feasible, but also that it should be a research priority.

Are adverse effects incorporated in economic models? An initial review of current practice.

PubMed

Craig, D; McDaid, C; Fonseca, T; Stock, C; Duffy, S; Woolacott, N

2009-12-01

To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of those models that included utilities derived them from patients on treatment and could therefore be interpreted as capturing adverse effects. In total, 30% of the models that included adverse effects used withdrawals related to drug toxicity and therefore might be interpreted as using withdrawals to capture adverse effects, but this was explicitly stated in only three reports. Of the 37 models that did not include adverse effects, 18 provided justification for this omission, most commonly lack of data; 19 appeared to make no explicit consideration of adverse effects in the model. There is an implicit assumption within modelling guidance that adverse effects are very important but there is a lack of clarity regarding how they should be dealt with and considered in modelling. In many cases a lack of clear reporting in the HTAs made it extremely difficult to ascertain what had actually been carried out in consideration of adverse effects. The main recommendation is for much clearer and explicit reporting of adverse effects, or their exclusion, in decision models and for explicit recognition in future guidelines that 'all relevant outcomes' should include some consideration of adverse events.

[Risk Management: concepts and chances for public health].

PubMed

Palm, Stefan; Cardeneo, Margareta; Halber, Marco; Schrappe, Matthias

2002-01-15

Errors are a common problem in medicine and occur as a result of a complex process involving many contributing factors. Medical errors significantly reduce the safety margin for the patient and contribute additional costs in health care delivery. In most cases adverse events cannot be attributed to a single underlying cause. Therefore an effective risk management strategy must follow a system approach, which is based on counting and analysis of near misses. The development of defenses against the undesired effects of errors should be the main focus rather than asking the question "Who blundered?". Analysis of near misses (which in this context can be compared to indicators) offers several methodological advantages as compared to the analysis of errors and adverse events. Risk management is an integral element of quality management.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Safety of benzathine penicillin for preventing congenital syphilis: a systematic review.

PubMed

Galvao, Tais F; Silva, Marcus T; Serruya, Suzanne J; Newman, Lori M; Klausner, Jeffrey D; Pereira, Mauricio G; Fescina, Ricardo

2013-01-01

To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis. We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses. From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low. Studies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

Concentrated liquid detergent pod ingestion in children.

PubMed

Sidhu, Natasha; Jaeger, Matthew W

2014-12-01

Concentrated liquid detergent pods are an emerging public health hazard, especially in pediatric patients. Ingestion is a more common route of exposure for liquid detergent pods compared with non-pod detergents and it tends to be associated with more severe adverse effects. We present 3 cases that demonstrate the varied clinical symptoms resulting from detergent pod ingestion. These cases not only demonstrate findings such as gastrointestinal and respiratory symptoms but also show more rare neurological symptoms. The cases highlight the dangers of concentrated liquid detergent pod ingestion. To help prevent further life-threatening injuries, there is a need for more consumer information and provider knowledge about the potential adverse complications.

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

PubMed

Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

2015-01-01

We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. 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. 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). We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.

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 reactions. The World Health Organization–Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results. PMID:26544039

Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database.

PubMed

O'Byrne, Michael L; Kim, Sunghee; Hornik, Christoph P; Yerokun, Babatunde A; Matsouaka, Roland A; Jacobs, Jeffrey P; Jacobs, Marshall L; Jonas, Richard A

2017-08-22

Extreme body mass index (BMI; either very high or very low) has been associated with increased risk of adverse perioperative outcome in adults undergoing cardiac surgery. The effect of BMI on perioperative outcomes in congenital heart disease patients has not been evaluated. A multicenter retrospective cohort study was performed studying patients 10 to 35 years of age undergoing a congenital heart disease operation in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 1, 2010, and December 31, 2015. The primary outcomes were operative mortality and a composite outcome (1 or more of operative mortality, major adverse event, prolonged hospital length of stay, and wound infection/dehiscence). The associations between age- and sex-adjusted BMI percentiles and these outcomes were assessed, with adjustment for patient-level risk factors, with multivariate logistic regression. Of 18 337 patients (118 centers), 16% were obese, 15% were overweight, 53% were normal weight, 7% were underweight, and 9% were severely underweight. Observed risks of operative mortality ( P =0.04) and composite outcome ( P <0.0001) were higher in severely underweight and obese subjects. Severely underweight BMI was associated with increased unplanned cardiac operation and reoperation for bleeding. Obesity was associated with increased risk of wound infection. In multivariable analysis, the association between BMI and operative mortality was no longer significant. Obese (odds ratio, 1.28; P =0.008), severely underweight (odds ratio, 1.29; P <0.0001), and underweight (odds ratio, 1.39; P =0.002) subjects were associated with increased risk of composite outcome. Obesity and underweight BMI were associated with increased risk of composite adverse outcome independently of other risk factors. Further research is necessary to determine whether BMI represents a modifiable risk factor for perioperative outcome. © 2017 American Heart Association, Inc.

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

PubMed

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

2018-03-26

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

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

Complementary and Alternative Medicine for Management of Premature Ejaculation: A Systematic Review.

PubMed

Cooper, Katy; Martyn-St James, Marrissa; Kaltenthaler, Eva; Dickinson, Kath; Cantrell, Anna; Ren, Shijie; Wylie, Kevan; Frodsham, Leila; Hood, Catherine

2017-03-01

Premature ejaculation (PE) is defined as ejaculation within 1 minute (lifelong PE) or 3 minutes (acquired PE), inability to delay ejaculation, and negative personal consequences. Management includes behavioral and pharmacologic approaches. To systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine in managing PE. Nine databases including Medline were searched through September 2015. Randomized controlled trials evaluating complementary and alternative medicine for PE were included. Studies were included if they reported on intravaginal ejaculatory latency time (IELT) and/or another validated PE measurement. Adverse effects were summarized. Ten randomized controlled trials were included. Two assessed acupuncture, five assessed Chinese herbal medicine, one assessed Ayurvedic herbal medicine, and two assessed topical "severance secret" cream. Risk of bias was unclear in all studies because of unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD] = 0.55 minute, P = .001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD = 0.80 minute, P = .001). Topical severance secret cream increased IELT over placebo in two studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes). Three studies comparing Chinese herbal medicine with selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) and over Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild. There is preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There are sparse data on adverse effects or potential for drug interactions. Further well-conducted randomized controlled trials would be valuable. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

PubMed

Goyer, Isabelle; Iseppon, Massimiliano; Thibault, Céline; Abaji, Rachid; Krajinovic, Maja; Autmizguine, Julie

2017-01-30

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Probable topiramate-induced diarrhea in a 2-month-old breast-fed child - A case report.

PubMed

Westergren, Tone; Hjelmeland, Knut; Kristoffersen, Bjørg; Johannessen, Svein Ivar; Kalikstad, Betty

2014-01-01

An infant developed a severe condition of recurrent and persistent watery diarrhea at 40 days of age. The child had been partially breast-fed, and the mother used topiramate for epilepsy. Hospital examination excluded a viral or bacterial infection and failed to identify any other potential cause. After two weeks, topiramate exposure was suspected to be the cause, and breast-feeding was suspended. The diarrhea ceased within 2 days. Analysis of the breast milk showed a topiramate concentration of 15.7 μmol/L (5.3 μg/mL). There is little information on the use of topiramate in breast-feeding women. The potential effects on the children are not known. Topiramate passes into breast milk, and the concentration may equal the therapeutic plasma concentration. In this case, the infant may have ingested up to 40% of the mother's weight-adjusted dose. Diarrhea is a well-known adverse reaction to topiramate and has the potential to cause serious electrolyte disturbances in neonates and infants. The condition improved rapidly after suspension of breast-feeding. Topiramate in breast milk may reach levels that cause adverse effects in infants. Based on the adverse reaction profile of topiramate and the milk concentration, the diarrhea was assessed as a probable adverse drug reaction in the infant.

Acetaminophen (paracetamol) oral absorption and clinical influences.

PubMed

Raffa, Robert B; Pergolizzi, Joseph V; Taylor, Robert; Decker, John F; Patrick, Jeffrey T

2014-09-01

Acetaminophen (paracetamol) is a widely used nonopioid, non-NSAID analgesic that is effective against a variety of pain types, but the consequences of overdose can be severe. Because acetaminophen is so widely available as a single agent and is increasingly being formulated in fixed-ratio combination analgesic products for the potential additive or synergistic analgesic effect and/or reduced adverse effects, accidental cumulative overdose is an emergent concern. This has rekindled interest in the sites, processes, and pharmacokinetics of acetaminophen oral absorption and the clinical factors that can influence these. The absorption of oral acetaminophen occurs primarily along the small intestine by passive diffusion. Therefore, the rate-limiting step is the rate of gastric emptying into the intestines. Several clinical factors can affect absorption per se or the rate of gastric emptying, such as diet, concomitant medication, surgery, pregnancy, and others. Although acetaminophen does not have the abuse potential of opioids or the gastrointestinal bleeding or organ adverse effects of NSAIDs, excess amounts can produce serious hepatic injury. Thus, an understanding of the sites and features of acetaminophen absorption--and how they might be influenced by factors encountered in clinical practice--is important for pain management using this agent. It can also provide insight for design of formulations that would be less susceptible to clinical variables. © 2013 World Institute of Pain.

Preliminary Experience with Transdermal Oxybutynin Patches for Hyperhidrosis.

PubMed

Bergón-Sendín, M; Pulido-Pérez, A; Sáez-Martín, L C; Suárez-Fernández, R

2016-12-01

Hyperhidrosis is very common and has a considerable impact on patients' quality of life. While oral oxybutynin is associated with good response rates, adverse effects are common and frequently cause patients to stop treatment. Following the recent launch of oxybutynin in a transdermal patch formulation in Spain, we undertook a preliminary study to assess treatment response and adverse effects in patients with hyperhidrosis. This prospective study of 25 patients treated twice weekly with transdermal oxybutynin patches over 10 weeks assessed treatment response on 2 subjective scales: the Hyperhidrosis Disease Severity Scale (HDSS) and a visual analog scale (VAS) for sweating. Sixty percent of patients showed an improvement in HDSS scores. VAS scores improved in all cases, and 68% of patients achieved a reduction of 3 points or more. Just 2 patients (8%) experienced treatment-related adverse effects (irritant dermatitis at the patch application site in both cases). Although our results are based on a small sample, they suggest that transdermal oxybutynin could be a useful option for the treatment of hyperhidrosis and that it has an excellent safety and tolerability profile. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Toxicities associated with NBOMe ingestion, a novel class of potent hallucinogens: A review of the literature

PubMed Central

Suzuki, Joji; Dekker, Michael A.; Valenti, Erin S.; Arbelo Cruz, Fabiola A.; Correa, Ady M.; Poklis, Justin L.; Poklis, Alphonse

2014-01-01

Objective A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion. Methods We searched the PubMed for relevant English language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted. Results Ten citations met criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analog identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Seven (35%) were discharged after a period of observation, while 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common laboratory abnormalities were elevated creatine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%). Conclusion NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens. PMID:25659919

Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm. f. juice in a 3-month drinking water toxicity study in F344 rats.

PubMed

Shao, A; Broadmeadow, A; Goddard, G; Bejar, E; Frankos, V

2013-07-01

Decolorized (purified, low anthraquinone) whole leaf Aloe vera (L.) Burm. f. juice was administered at concentrations of 0%, 0.5%, 1% and 2% in the drinking water of F344Du rats for 3 months without any adverse effect. The no-observed-adverse-effect level (NOAEL) in this study was considered to be >2%w/v (>1845 mg/kg bodyweight/day for males and >2920 mg/kg bodyweight for females). The test material contained total anthraquinones at <0.1 parts per million. In the present study there was a complete absence of any histological alteration in samples from the cecum, colon (proximal, mid and distal regions). Similar concentrations of non-decolorized (unpurified, high anthraquinone) Aloe vera extracts tested in other studies have resulted in an increased incidence and severity of diarrhea and colon adenomas and carcinomas. The results of this study supports the assertion that the high levels of anthraquinone present in orally administered, non-purified whole leaf Aloe vera extract may be responsible for the adverse effects observed on the colon. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neurological Disorders in Medical Use of Cannabis: An Update.

PubMed

Solimini, Renata; Rotolo, Maria Concetta; Pichini, Simona; Pacifici, Roberta

2017-01-01

Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A patient case highlighting the myriad of cutaneous adverse effects of prolonged use of hydroxyurea.

PubMed

Neill, Brett; Ryser, Ted; Neill, John; Aires, Daniel; Rajpara, Anand

2017-11-15

Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer. We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up. We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Potential therapeutic effects of mTOR inhibition in atherosclerosis

PubMed Central

Kurdi, Ammar; De Meyer, Guido R. Y.

2015-01-01

Despite significant improvement in the management of atherosclerosis, this slowly progressing disease continues to affect countless patients around the world. Recently, the mechanistic target of rapamycin (mTOR) has been identified as a pre‐eminent factor in the development of atherosclerosis. mTOR is a constitutively active kinase found in two different multiprotein complexes, mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the value of mTORC1 inhibition to prevent the development of atherosclerotic plaques in several animal models. Rapalog‐eluting stents have also shown extraordinary results in humans, even though the exact mechanism for this anti‐atherosclerotic effect remains elusive. Unfortunately, rapalogs are known to trigger diverse undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These adverse effects include dyslipidaemia and insulin resistance, both known triggers of atherosclerosis. Several strategies, such as combination therapy with statins and metformin, have been suggested to oppose rapalog‐mediated adverse effects. Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine monophosphate‐activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis. Intermittent regimens and dose reduction have also been proposed to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2‐related side effects. PMID:26551391

[Intractable diarrhoea and severe weight loss by roflumilast].

PubMed

Horna, Oihana; Toyas, Carla

2013-08-04

Roflumilast is a recently marketed drug, indicated for maintenance treatment of severe chronic obstructive pulmonary disease associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment. The safety data of this drug have always been subjected to controversy and concerns. The Food and Drug Administration rejected the drug after the first evaluation, asking the company to clarify the adverse reactions during the investigation process, the European Medicines Agency approved the drug including a Risk Management Plan, designed to promote a safe use of the drug. During the first months after the marketing process, the Spanish Pharmacovigilance System has already been acquainted of several adverse events notifications; therefore, these patients may be closely monitored, mainly because of digestive and psychiatric disorders. Here we report the case of a female patient who showed a serious digestive clinical profile and a severe weight loss, more than 25% of her initial weight, when a treatment with roflumilast was started. The suspicion of a side effect as the cause of the reported clinical profile and its resolution required 3 hospital admissions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial.

PubMed

Hay, Alastair D; Little, Paul; Harnden, Anthony; Thompson, Matthew; Wang, Kay; Kendrick, Denise; Orton, Elizabeth; Brookes, Sara T; Young, Grace J; May, Margaret; Hollinghurst, Sandra; Carroll, Fran E; Downing, Harriet; Timmins, David; Lafond, Natasher; El-Gohary, Magdy; Moore, Michael

2017-08-22

Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, -0.20; 95% CI, -0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events. Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity. ISRCTN.com Identifier: ISRCTN57309858.

75 FR 30841 - Advisory Commission on Childhood Vaccines; Request for Nominations for Voting Members

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... that result in fewer or no significant adverse reactions; surveying Federal, State, and local programs... childhood vaccines, including the adverse reaction reporting requirements of section 2125(b); advising the... frequency and severity of adverse reactions associated with childhood vaccines; consulting on the...

Grapefruit and drug interactions.

PubMed

2012-12-01

Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few reports involving severe clinical consequences have been published, they suggest that grapefruit juice should be avoided during drug therapy, especially when the drug has a narrow therapeutic margin or carries a risk of serious dose-dependent adverse effects. Patients should be informed of this risk whenever a drug is prescribed or dispensed.

Traditional chinese medicine Xuebijing treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning.

PubMed

Gong, Ping; Lu, Zhidan; Xing, Jing; Wang, Na; Zhang, Yu

2015-01-01

Paraquat poisoning causes multiple organ injury and high mortality due to severe toxicity and lack of effective treatment. Xuebijing (XBJ) injection, a traditional Chinese medicine preparation of five Chinese herbs (Radix Salviae Miltiorrhiae, Rhizoma Chuanxiong, Flos Carthami, Angelica Sinensis and Radix Paeoniae Rubra), has an anti-inflammatory effect and is widely used in the treatment of sepsis. This retrospective study was designed to evaluate the effects of XBJ combined with conventional therapy on mortality risk of patients with acute paraquat poisoning. Out of 68 patients, 27 were treated with conventional therapy (control group) and 41 were treated with intravenous administration of XBJ (100 ml, twice a day, up to 7 days) plus conventional therapy (XBJ group). Vital organ function, survival time within 28 days and adverse events during the treatment were reviewed. Results indicated that XBJ treatment significantly increased median survival time among patients ingesting 10-30 ml of paraquat (P=0.02) compared with the control group. After adjustment for covariates, XBJ treatment was associated significantly with a lower mortality risk (adjusted HR 0.242, 95% CI 0.113 to 0.516, P=0.001) compared with the control group. Additionally, compared with Day 1, on Day 3 the value of PaO2/FiO2 was significantly decreased, and the values of serum alanine aminotransferase, creatinine and troponin T were significantly increased in the control group (all P<0.05), but these values were significant improved in the XBJ group (all P<0.05). Only one patient had skin rash with itch within 30 minutes after injection and no severe adverse events were found in the XBJ group. In conclusion, XBJ treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning, which may be attributed to improved function of vital organs with no severe adverse events.

Traditional Chinese Medicine Xuebijing Treatment Is Associated with Decreased Mortality Risk of Patients with Moderate Paraquat Poisoning

PubMed Central

Gong, Ping; Xing, Jing; Wang, Na

2015-01-01

Paraquat poisoning causes multiple organ injury and high mortality due to severe toxicity and lack of effective treatment. Xuebijing (XBJ) injection, a traditional Chinese medicine preparation of five Chinese herbs (Radix Salviae Miltiorrhiae, Rhizoma Chuanxiong, Flos Carthami, Angelica Sinensis and Radix Paeoniae Rubra), has an anti-inflammatory effect and is widely used in the treatment of sepsis. This retrospective study was designed to evaluate the effects of XBJ combined with conventional therapy on mortality risk of patients with acute paraquat poisoning. Out of 68 patients, 27 were treated with conventional therapy (control group) and 41 were treated with intravenous administration of XBJ (100 ml, twice a day, up to 7 days) plus conventional therapy (XBJ group). Vital organ function, survival time within 28 days and adverse events during the treatment were reviewed. Results indicated that XBJ treatment significantly increased median survival time among patients ingesting 10-30 ml of paraquat (P=0.02) compared with the control group. After adjustment for covariates, XBJ treatment was associated significantly with a lower mortality risk (adjusted HR 0.242, 95% CI 0.113 to 0.516, P=0.001) compared with the control group. Additionally, compared with Day 1, on Day 3 the value of PaO2/FiO2 was significantly decreased, and the values of serum alanine aminotransferase, creatinine and troponin T were significantly increased in the control group (all P<0.05), but these values were significant improved in the XBJ group (all P<0.05). Only one patient had skin rash with itch within 30 minutes after injection and no severe adverse events were found in the XBJ group. In conclusion, XBJ treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning, which may be attributed to improved function of vital organs with no severe adverse events. PMID:25923333

Effect of triptorelin on lower urinary tract symptoms in Australian prostate cancer patients

PubMed Central

Woo, Henry H; Murphy, Declan G; Testa, Gerard M; Grummet, Jeremy P; Chong, Michael; Stork, Andrew P

2017-01-01

Purpose Prostate cancer is often comorbidly associated with lower urinary tract symptoms (LUTS), but few studies have assessed the effects of androgen deprivation therapy on LUTS in this patient group. Patients and methods We conducted a prospective, noninterventional, multicenter, observational study to assess the effectiveness of triptorelin (11.25 mg every 12 weeks) over 48 weeks in men presenting with local stage T3/4 prostate cancer and moderate to severe LUTS (International Prostate Symptom Score [IPSS] >7) in a routine practice setting in Australia. Results Of the 44 men who enrolled, effectiveness data were available for 39 men. By the end of the study, 30% of men no longer met the IPSS criteria for moderate to severe LUTS. The proportion of patients with moderate to severe LUTS was 69.6% (16/23) at week 48 and 76.9% (30/39) at the last available visit (coprimary outcomes). An IPSS reduction of ≥3 from week 0 was observed in 47% of men at week 4, 56% at week 24, 61% (14/23) at week 48, and 61.5% (24/39) at the last available visit. Quality of life was rated as mostly satisfied-to-delighted by 39.5% of patients at week 0, 53.9% at week 24, and 77.3% at week 48. Triptorelin was well tolerated with 8 treatment-related adverse events reported, half of which were hot flushes; 5 patients discontinued due to the reported treatment-related adverse events. Conclusion This observational study suggests that triptorelin improves moderate to severe LUTS in prostate cancer patients in a routine clinical practice setting. PMID:28261572

Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS.

PubMed

Mori, Masato; Yamagata, Takanori; Goto, Tamako; Saito, Shigeko; Momoi, Mariko Y

2004-10-01

The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 microg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required.

Effect of overtime work on 24-hour ambulatory blood pressure.

PubMed

Hayashi, T; Kobayashi, Y; Yamaoka, K; Yano, E

1996-10-01

Recently, the adverse effects of long working hours on the cardiovascular systems of workers in Japan, including "Karoshi" (death from overwork), have been the focus of social concern. However, conventional methods of health checkups are often unable to detect the early signs of such adverse effects. To evaluate the influence of overtime work on the cardiovascular system, we compared 24-hour blood pressure measurements among several groups of male white-collar workers. As a result, for those with normal blood pressure and those with mild hypertension, the 24-hour average blood pressure of the overtime groups was higher than that of the control groups; for those who periodically did overtime work, the 24-hour average blood pressure and heart rate during the busy period increased. These results indicate that the burden on the cardiovascular system of white-collar workers increases with overtime work.

Calcium and zinc DTPA administration for internal contamination with plutonium-238 and americium-241.

PubMed

Kazzi, Ziad N; Heyl, Alexander; Ruprecht, Johann

2012-08-01

The accidental or intentional release of plutonium or americium can cause acute and long term adverse health effects if they enter the human body by ingestion, inhalation, or injection. These effects can be prevented by rapid removal of these radionuclides by chelators such as calcium or zinc diethylenetriaminepentaacetate (calcium or zinc DTPA). These compounds have been shown to be efficacious in enhancing the elimination of members of the actinide family particularly plutonium and americium when administered intravenously or by nebulizer. The efficacy and adverse effects profile depend on several factors that include the route of internalization of the actinide, the type, and route time of administration of the chelator, and whether the calcium or zinc salt of DTPA is used. Current and future research efforts should be directed at overcoming limitations associated with the use of these complex drugs by using innovative methods that can enhance their structural and therapeutic properties.

The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results.

PubMed

Politis, C; Wiersum, J C; Richardson, C; Robillard, P; Jorgensen, J; Renaudier, P; Faber, J-C; Wood, E M

2016-11-01

The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety. © 2016 International Society of Blood Transfusion.

Leveraging graph topology and semantic context for pharmacovigilance through twitter-streams.

PubMed

Eshleman, Ryan; Singh, Rahul

2016-10-06

Adverse drug events (ADEs) constitute one of the leading causes of post-therapeutic death and their identification constitutes an important challenge of modern precision medicine. Unfortunately, the onset and effects of ADEs are often underreported complicating timely intervention. At over 500 million posts per day, Twitter is a commonly used social media platform. The ubiquity of day-to-day personal information exchange on Twitter makes it a promising target for data mining for ADE identification and intervention. Three technical challenges are central to this problem: (1) identification of salient medical keywords in (noisy) tweets, (2) mapping drug-effect relationships, and (3) classification of such relationships as adverse or non-adverse. We use a bipartite graph-theoretic representation called a drug-effect graph (DEG) for modeling drug and side effect relationships by representing the drugs and side effects as vertices. We construct individual DEGs on two data sources. The first DEG is constructed from the drug-effect relationships found in FDA package inserts as recorded in the SIDER database. The second DEG is constructed by mining the history of Twitter users. We use dictionary-based information extraction to identify medically-relevant concepts in tweets. Drugs, along with co-occurring symptoms are connected with edges weighted by temporal distance and frequency. Finally, information from the SIDER DEG is integrate with the Twitter DEG and edges are classified as either adverse or non-adverse using supervised machine learning. We examine both graph-theoretic and semantic features for the classification task. The proposed approach can identify adverse drug effects with high accuracy with precision exceeding 85 % and F1 exceeding 81 %. When compared with leading methods at the state-of-the-art, which employ un-enriched graph-theoretic analysis alone, our method leads to improvements ranging between 5 and 8 % in terms of the aforementioned measures. Additionally, we employ our method to discover several ADEs which, though present in medical literature and Twitter-streams, are not represented in the SIDER databases. We present a DEG integration model as a powerful formalism for the analysis of drug-effect relationships that is general enough to accommodate diverse data sources, yet rigorous enough to provide a strong mechanism for ADE identification.

The novel antiarrhythmic drug dronedarone: comparison with amiodarone.

PubMed

Kathofer, Sven; Thomas, Dierk; Karle, Christoph A

2005-01-01

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.

Correlates of adverse childhood experiences among adults with severe mood disorders.

PubMed

Lu, Weili; Mueser, Kim T; Rosenberg, Stanley D; Jankowski, Mary Kay

2008-09-01

Adverse childhood experiences have been found to be associated with poor physical and poor mental health, impaired functioning, and increased substance abuse in the general adult population. The purpose of this study was to examine the clinical correlates of these experiences among adults with severe mood disorders. Adverse childhood experiences (including physical abuse, sexual abuse, parental mental illness, loss of parent, parental separation or divorce, witnessing domestic violence, and placement in foster or kinship care) were assessed retrospectively in a sample of 254 adults with major mood disorders. The relationships between cumulative exposure to these experiences and psychiatric problems, health, substance use disorders, community functioning, trauma exposure in adulthood, and high-risk behaviors were examined. Increased exposure to childhood adverse experiences was related to high-risk behaviors, diagnosis of a substance use disorder, exposure to trauma in adulthood, psychiatric problems (younger age at first hospitalization, number of suicide attempts, and diagnosis of posttraumatic stress disorder), medical service utilization, and homelessness. The findings extend research in the general population by suggesting that adverse childhood experiences contribute to worse mental and physical health and functional outcomes among adults with severe mood disorders.

The effects of perceived racism on psychological distress mediated by venting and disengagement coping in Native Hawaiians.

PubMed

Kaholokula, Joseph Keawe'aimoku; Antonio, Mapuana C K; Ing, Claire K Townsend; Hermosura, Andrea; Hall, Kimberly E; Knight, Rebecca; Wills, Thomas A

2017-01-12

Studies have linked perceived racism to psychological distress via certain coping strategies in several different racial and ethnic groups, but few of these studies included indigenous populations. Elucidating modifiable factors for intervention to reduce the adverse effects of racism on psychological well-being is another avenue to addressing health inequities. We examined the potential mediating effects of 14 distinct coping strategies on the relationship between perceived racism and psychological distress in a community-based sample of 145 Native Hawaiians using structural equation modeling. Perceived racism had a significant indirect effect on psychological distress, mediated through venting and behavioral disengagement coping strategies, with control for age, gender, educational level, and marital status. The findings suggest that certain coping strategies may exacerbate the deleterious effects of racism on a person's psychological well-being. Our study adds Native Hawaiians to the list of U.S. racial and ethnic minorities whose psychological well-being is adversely affected by racism.

Economic and clinical aspects of intravenous versus oral busulfan in adult patients for conditioning prior to HSCT.

PubMed

Berger, Karin; Schopohl, Dorothee; Rieger, Christina; Ostermann, Helmut

2015-12-01

Busulfan (BU) used as cytoreductive conditioning prior to hematopoietic stem cell transplantation (HSCT) is available as intravenous (IV) and oral (O) preparation. IV-BU has clinical advantages associated with relevant incremental costs. The aim was to determine the economic impact of IV-BU versus O-BU in adult HSCT recipients from a German health care providers' perspective. A budget-impact model (BIM) including costs and risks for oral mucositis (OM), infection with OM, and hepatic sinusoidal obstruction syndrome (SOS) was developed. Model inputs are literature data comparing clinical effects of IV-BU versus O-BU and German cost data (conditioning therapy, treatment of OM, infections, SOS without/with multiorgan failure) from literature and tariff lists. Base case calculations resulted the following: total costs of adverse events were €86,434 with O-BU and €44,376 with IV-BU for ten patients each. Considering costs of adverse events and drugs, about €5840 for ten patients receiving IV-BU are saved. Sensitivity analyses were conducted in several ways. Cost savings range between €4910 and €12,640 per ten patients for all adverse events and €2070 or €1140 per ten patients considering SOS only. Drug treatment of SOS and treatment of multiorgan failure during severe SOS are major cost drivers. Worst case scenario calculations (assuming -25% risk of all adverse events for O-BU and +25% for IV-BU) yield up to €27,570 per ten patients with IV-BU. Considering costs of adverse events and drugs, IV-BU is the dominant alternative from a German providers' perspective. For more comprehensive economic evaluations, additional epidemiological data, evidence on clinical outcomes, patient-reported outcomes, and treatment patterns are needed.

Preoperative Determinants of Outcomes of Infant Heart Surgery in a Limited-Resource Setting.

PubMed

Reddy, N Srinath; Kappanayil, Mahesh; Balachandran, Rakhi; Jenkins, Kathy J; Sudhakar, Abish; Sunil, G S; Raj, R Benedict; Kumar, R Krishna

2015-01-01

We studied the effect of preoperative determinants on early outcomes of 1028 consecutive infant heart operations in a limited-resource setting. Comprehensive data on pediatric heart surgery (January 2010-December 2012) were collected prospectively. Outcome measures included in-hospital mortality, prolonged ventilation (>48 hours), and bloodstream infection (BSI) after surgery. Preoperative variables that showed significant individual association with outcome measures were entered into a logistic regression model. Weight at birth was low in 224 infants (21.8%), and failure to thrive was common (mean-weight Z score at surgery was 2.72 ± 1.7). Preoperatively, 525 infants (51%) needed intensive care, 69 infants (6.7%) were ventilated, and 80 infants (7.8%) had BSI. In-hospital mortality (4.1%) was significantly associated with risk adjustment for congenital heart surgery-1 (RACHS-1) risk category (P < 0.001). Neonatal status, preoperative BSI, and requirement of preoperative intensive care and ventilation had significant individual association with adverse outcomes, whereas low birth weight, prematurity, and severe failure to thrive (weight Z score <-3) were not associated with adverse outcomes. On multivariable logistic regression analysis, preoperative sepsis (odds ratio = 2.86; 95% CI: 1.32-6.21; P = 0.008) was associated with mortality. Preoperative intensive care unit stay, ventilation, BSI, and RACHS-1 category were associated with prolonged postoperative ventilation and postoperative sepsis. Neonatal age group was additionally associated with postoperative sepsis. Although severe failure to thrive was common, it did not adversely affect outcomes. In conclusions, preoperative BSI, preoperative intensive care, and mechanical ventilation are strongly associated with adverse outcomes after infant cardiac surgery in this large single-center experience from a developing country. Failure to thrive and low birth weight do not appear to adversely affect surgical outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2010-01-01

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

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

PubMed

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

2016-11-22

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

Circumpolar contaminant concentrations in polar bears (Ursus maritimus) and potential population-level effects.

PubMed

Nuijten, R J M; Hendriks, A J; Jenssen, B M; Schipper, A M

2016-11-01

Polar bears (Ursus maritimus) currently receive much attention in the context of global climate change. However, there are other stressors that might threaten the viability of polar bear populations as well, such as exposure to anthropogenic pollutants. Lipophilic organic compounds bio-accumulate and bio-magnify in the food chain, leading to high concentrations at the level of top-predators. In Arctic wildlife, including the polar bear, various adverse health effects have been related to internal concentrations of commercially used anthropogenic chemicals like PCB and DDT. The extent to which these individual health effects are associated to population-level effects is, however, unknown. In this study we assembled data on adipose tissue concentrations of ∑PCB, ∑DDT, dieldrin and ∑PBDE in individual polar bears from peer-reviewed scientific literature. Data were available for 14 out of the 19 subpopulations. We found that internal concentrations of these contaminants exceed threshold values for adverse individual health effects in several subpopulations. In an exploratory regression analysis we identified a clear negative correlation between polar bear population density and sub-population specific contaminant concentrations in adipose tissue. The results suggest that adverse health effects of contaminants in individual polar bears may scale up to population-level consequences. Our study highlights the need to consider contaminant exposure along with other threats in polar bear population viability analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work

PubMed Central

Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

2016-01-01

Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts. PMID:27242616

Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work.

PubMed

Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

2016-01-01

Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts.

Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

PubMed Central

Thellier, Marc; Ndour, Papa Alioune; Ader, Flavie; Roussel, Camille; Sonneville, Romain; Mayaux, Julien; Matheron, Sophie; Angoulvant, Adela; Wyplosz, Benjamin; Rapp, Christophe; Pistone, Thierry; Lebrun-Vignes, Bénédicte; Kendjo, Eric; Danis, Martin; Houzé, Sandrine; Bricaire, François; Mazier, Dominique; Buffet, Pierre; Caumes, Eric

2015-01-01

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate. PMID:25898007

Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo.

PubMed

Hirobe, Sachiko; Otsuka, Risa; Iioka, Hiroshi; Quan, Ying-Shu; Kamiyama, Fumio; Asada, Hideo; Okada, Naoki; Nakagawa, Shinsaku

2017-01-01

Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo. ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed. Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects. These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo. Copyright © 2016 Elsevier Inc. All rights reserved.