An unintended consequence of electronic prescriptions: prevalence and impact of internal discrepancies

PubMed Central

Palchuk, Matvey B; Fang, Elizabeth A; Cygielnik, Janet M; Labreche, Matthew; Shubina, Maria; Ramelson, Harley Z; Hamann, Claus; Broverman, Carol; Einbinder, Jonathan S

2010-01-01

Many e-prescribing systems allow for both structured and free-text fields in prescriptions, making possible internal discrepancies. This study reviewed 2914 electronic prescriptions that contained free-text fields. Internal discrepancies were found in 16.1% of the prescriptions. Most (83.8%) of the discrepancies could potentially lead to adverse events and many (16.8%) to severe adverse events, involving a hospital admission or death. Discrepancies in doses, routes or complex regimens were most likely to have a potential for a severe event (p=0.0001). Discrepancies between structured and free-text fields in electronic prescriptions are common and can cause patient harm. Improvements in electronic medical record design are necessary to minimize the risk of discrepancies and resulting adverse events. PMID:20595316

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

[Acute renal insufficiency caused by phenyl-indane-dione. Apropos of 1 case].

PubMed

Horellou, M F; Feiss, P; Voultoury, J C; Gay, R

1978-01-01

One case of Phenindione (PID) adverse reaction is reported. The patient showed a typical picture of immunological reaction to the drug. In spite of severe bacteremia, she recovered. Only 33 cases of PID intolerance are reported in the literature. In all these patients, renal failure occurred. Superinfection is the most frequent cause of death. PID adverse reaction should be evoqued in the presence of signs such a fever, asthenia, anorexia and cutaneous reaction. The PID should be stopped immediatly but renal failure yet develops. During a PID treatment, frequent evaluation of blood azotemia, creatinine and proteinuria should be performed.

Recent advances in the understanding of severe cutaneous adverse reactions.

PubMed

Adler, N R; Aung, A K; Ergen, E N; Trubiano, J; Goh, M S Y; Phillips, E J

2017-11-01

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients. © 2017 British Association of Dermatologists.

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.

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

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.

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.

Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function

PubMed Central

McGregor, JulieAnne G.; Negrete-Lopez, Roberto; Poulton, Caroline J.; Kidd, Jason M.; Katsanos, Suzanne L.; Goetz, Lindsey; Hu, Yichun; Nachman, Patrick H.; Falk, Ronald J.; Hogan, Susan L.

2015-01-01

Background Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV. Methods Biopsy-proven AAV patients (diagnosed 1/1991–6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1–2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals. Results A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1–2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0–8.7; P = 0.001). Conclusions More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity. PMID:25805747

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.

[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.

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.

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.

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.

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.

Self-reported adverse reactions associated with mycoprotein (Quorn-brand) containing foods.

PubMed

Jacobson, Michael F; DePorter, Janna

2018-06-01

Mycoprotein, which is produced by a mold and is the basis of Quorn-brand meat substitutes, is a novel cause of allergic and gastrointestinal reactions, but little information has been available on its associated symptomatology. To describe the nature and frequency of adverse reactions to mycoprotein. Self-reports of adverse reactions to mycoprotein were collected via a Web-based questionnaire (www.quorncomplaints.org) and then analyzed. Analysis of 1,752 adverse reactions found that Quorn products caused allergic and gastrointestinal symptoms, with some people experiencing both. Allergic reactions, including urticaria and anaphylaxis, occurred within 4 hours of consumption in 312 people. Of those reactions, 45.8%, 1 fatal, began within 1 hour of exposure. Of those 312 individuals, 188 (60.3%) reported repeated reactions after repeated consumption of Quorn, and 2 people experienced 8 reactions (13 people did not say whether they experienced more than 1 reaction). Quorn foods caused gastrointestinal symptoms, including emesis and diarrhea, within 8 hours of consumption in 1,692 people. Of the gastrointestinal symptoms, 66.6% occurred 46 to 180 minutes after consumption of the products. Symptoms ranged from mild nausea to emesis severe enough to warrant medical attention. Mycoprotein may be causing numerous and sometimes life-threatening allergic and gastrointestinal reactions. The acceptance in the food supply of this nonessential ingredient deserves reconsideration. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Changing water cycle over Korea

NASA Astrophysics Data System (ADS)

Yoon, J.

2017-12-01

In 2015, Korea experienced relatively strong drought, and annual mean precipitation was the third lowest since observation started at 1969 causing adverse impact on the several sectors including farming industry. Most precipitation in Korea occurs during summer season. In case of 2015 Korean drought, summer rainfall was much below than normal. On the other hand, another severe drought occurred in 2017 spring, which was followed by a couple of heavy rainfall cases that caused human casualties and damage in various sectors. Here we want to analyze this fast shifting of water cycle over Korea with a focus on its causing mechanisms and large scale atmospheric circulation features.

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.

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.

Human Parechovirus Meningitis with Adverse Neurodevelopmental Outcome: A Case Report.

PubMed

Berk, Mylene C; Bruning, Andrea Hl; van Wassenaer-Leemhuis, Aleid G; Wolthers, Katja C; Pajkrt, Dasja

2018-03-14

Human parechovirus (HPeV) infections usually cause mild symptoms in children. Although their contribution to severe disease in young children - such as neonatal sepsis and meningo-encephalitis - is increasingly recognized, data on long-term consequences are scarce. Here we present the case of a five-year old boy with severe long-term neurodevelopmental sequelae following HPeV-3 meningitis.

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.

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

A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry?

PubMed

Bushe, Chris J; Bradley, Andrew; Pendlebury, John

2010-07-01

Hyperprolactinaemia is a common adverse event reported in association with treatments used in schizophrenia and bipolar disorder. Recent data are suggestive that hyperprolactinaemia may have a range of significant short-and long-term clinical consequences. The objective of this review is to examine the causes, frequency and clinical consequences of hyperprolactinaemia in the severely mentally ill (SMI) with a focus on patients taking antipsychotic medications. A Medline search was carried out to identify relevant publications. Reference lists from previous review articles were also examined to search for additional data. Hyperprolactinaemia may be one of the most common adverse events associated with some antipsychotic medications. Precise rates with individual drugs had however until recently been poorly categorized. The relationship between hyperprolactinaemia and adverse outcomes in the SMI population appears similar to that in the general population. Adverse outcomes (such as sexual dysfunction) can occur acutely and in the longer term (bone fractures and possibly breast cancer), but the precise link between degree and length of hyperprolactinaemia and adverse outcome remains to be established. In conclusion, hyperprolactinaemia is a common treatment-emergent adverse event of some antipsychotic medications and may have clinical consequences. Physicians must balance the benefits and risks of treatment when determining appropriate therapy for individual patients.

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.

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...

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.

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.

Increased Non-conducted P-wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

EPA Science Inventory

Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that ar...

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.

Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

PubMed

Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

2016-03-16

Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

Severe non-anion gap metabolic acidosis induced by topiramate: a case report.

PubMed

Shiber, Joseph R

2010-05-01

A non-anion gap acidosis can be induced by topiramate, causing symptomatic dyspnea and confusion. Discuss the pathophysiology of the hyperchloremic metabolic acidosis caused by topiramate, the typical clinical presentation, and the recommended treatment. This case presents a young woman with a clinically significant non-anion gap metabolic acidosis believed to be caused by topiramate. She had been taking the medication for several months without prior adverse effects. Once she began having dyspnea as a respiratory response to the renal tubule acidosis, she had decreased oral intake of food and fluids, which induced a pre-renal acute renal failure that worsened her acidemia. In the Emergency Department, she received intravenous fluids and sodium bicarbonate, and later was intubated for mechanical ventilation due to respiratory fatigue. With the topiramate withdrawn, the patient had a full recovery of her renal function and metabolic acid-base status over the next 72 h. This case serves to increase awareness of this possible adverse effect and the recommended treatment as topiramate becomes more widely used. Topiramate can induce a renal tubule acidosis resulting in a hyperchloremic metabolic acidosis. Recognition of the underlying cause is crucial so that the drug can be withdrawn while supportive care is provided. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The relevance of cytochrome P450 polymorphism in forensic medicine and akathisia-related violence and suicide.

PubMed

Eikelenboom-Schieveld, Selma J M; Lucire, Yolande; Fogleman, James C

2016-07-01

Adverse drug reactions and interactions are among the major causes of death in the United States. Antidepressants have been reported as causing suicide and homicide and share the class attribute of frequently producing akathisia, a state of severe restlessness associated with thoughts of death and violence. Medical examiners can now identify some pharmacogenetic interactions that cause drugs, deemed safe for most, to be lethal to others. Such deaths do not yet include medication-induced, akathisia-related suicides and homicides. An extrapyramidal side effect, akathisia is a manifestation of drug toxicity whose causes lie, inter alia, in drugs, doses, and co-prescribed medications that inhibit and compete for metabolizing enzymes, which may themselves be defective. In this paper, we report our investigation into adverse drug reactions/interactions in three persons who committed homicide, two also intending suicide, while on antidepressants prescribed for stressful life events. Their histories of medication use, adverse reactions and reasons for changes in medications are presented. DNA samples were screened for variants in the cytochrome P450 gene family; that produce drug metabolizing enzymes. All three cases exhibit genotype-based diminished metabolic capability that, in combination with their enzyme inhibiting/competing medications, decreased metabolism further and are the likely cause of these catastrophic events. Copyright © 2016 The Authors. Published by Elsevier Ltd.. 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...

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)

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

PubMed

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

2010-01-01

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

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.

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

Indirect causes of severe adverse maternal outcomes: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

PubMed

Lumbiganon, P; Laopaiboon, M; Intarut, N; Vogel, J P; Souza, J P; Gülmezoglu, A M; Mori, R

2014-03-01

To assess the proportion of severe maternal outcomes resulting from indirect causes, and to determine pregnancy outcomes of women with indirect causes. Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health. A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East. A total of 314 623 pregnant women admitted to the participating facilities. We identified the percentage of women with severe maternal outcomes arising from indirect causes. We evaluated the risk of severe maternal and perinatal outcomes in women with, versus without, underlying indirect causes, using adjusted odds ratios and 95% confidence intervals, by a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities. Severe maternal outcomes and preterm birth, fetal mortality, early neonatal mortality, perinatal mortality, low birthweight, and neonatal intensive care unit admission. Amongst 314 623 included women, 2822 were reported to suffer from severe maternal outcomes, out of which 20.9% (589/2822; 95% CI 20.1-21.6%) were associated with indirect causes. The most common indirect cause was anaemia (50%). Women with underlying indirect causes showed significantly higher risk of obstetric complications (adjusted odds ratio, aOR, 7.0; 95% CI 6.6-7.4), severe maternal outcomes (aOR 27.9; 95% CI 24.7-31.6), and perinatal mortality (aOR 3.8; 95% CI 3.5-4.1). Indirect causes were responsible for about one-fifth of severe maternal outcomes. Women with underlying indirect causes had significantly increased risks of severe maternal and perinatal outcomes. © 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

[Which hip articulation bearing for which patient? : Tribology of the future].

PubMed

Morlock, M M; Bishop, N; Kaddick, C

2011-12-01

Replacement of the hip joint has become an exceptionally successful procedure since the inauguration of the low friction principle by Charnley. Aseptic osteolysis and joint dislocation have been addressed by the development of wear-optimized materials and the introduction of larger heads. As an increase in head diameter against polyethylene causes wear increase, larger hard-on-hard bearings were introduced, which exhibit reduced wear and reduced dislocation risk with increasing head diameter. These findings were derived from standard simulator testing, not sufficiently considering the risk of fluid film breakdown under adverse conditions, which can cause a dramatic increase in wear and friction proportional to the head diameter. Such adverse conditions can occur clinically in patients due to several factors and have caused the presently observed unexpected problems with these new designs. Standardized preclinical testing has to be viewed as a minimum requirement but certainly not as a guarantee for the clinical success of new materials and designs even if the testing is adapted to the current patient requirements, which is presently not the case. The future of tribology lies in the prevention of adverse conditions in patients, the improvement and optimized use of proven existing materials and not in the use of new materials.

Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway.

PubMed

Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

2017-12-01

According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

Stress, Behavior and Health: Developing a Model for Predicting Post-Deployment Morbidity, Mortality, and Other Adverse Outcomes

DTIC Science & Technology

2000-07-01

contact dermatitis and other eczema , unspecified cause (692.9), primary localized osteoarthrosis (715.18), osteoarthrosis, unspecified whether...34 Several studies have documented an association between exposures to emotional or physical trauma and increased use of alcohol or other substances (54-58

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...

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...

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.

A Review of Adverse Effects of Road Traffic Noise on Human Health

NASA Astrophysics Data System (ADS)

Singh, Devi; Kumari, Neeraj; Sharma, Pooja

Noise pollution due to road traffic is a potential threat to human health. Since it is a global hazard, the rapid urbanization and exponential traffic growth have aggravated the problem. Population residing along the busy traffic lanes is continuously exposed to the sound levels which are above the permissible limits. This constant exposure to noise pollution is a cause of concern as it leads to several adverse impacts on human health. Traffic noise causes irritation and annoyance, sleep disturbances, cardiovascular disease, risk of stroke, diabetes, hypertension and loss of hearing. It results in decreased work performance. The present review highlights the serious health hazards of road traffic noise (RTN) which needs to be curbed. Preventive measures of noise pollution can help in combating noise-induced health hazards and increased work performance.

Role of dermatology in pharmacogenomics: drug-induced skin injury.

PubMed

Borroni, Riccardo G

2015-01-01

Different individuals may respond diversely to the same drug, in terms of efficacy and toxicity. Adverse drug reactions cause about 6% of all hospital admissions and account for up to 9% of hospitalization costs. Drug-induced skin injury (DISI) is the most common presentation of adverse drug reactions, ranging from maculopapular eruptions to severe adverse cutaneous drug reactions (SCARs) with mortality of up to 40%. Specific genetic polymorphisms confer susceptibility to different types of DISI. Identifying patients genetically at risk for SCARs is one of the goals of pharmacogenomics. In this article, the aspects of clinical dermatology relevant to the pharmacogenetics of DISI are reviewed. Many SCARs are now preventable, with consequent reduction of morbidity, mortality and healthcare costs.

Association of anemia with the risk of cardiovascular adverse events in overweight/obese patients.

PubMed

Winther, S A; Finer, N; Sharma, A M; Torp-Pedersen, C; Andersson, C

2014-03-01

Anemia is associated with increased cardiovascular risks. Obesity may cause anemia in several ways, for example, by low-grade inflammation and relative iron deficit. The outcomes associated with anemia in overweight/obese patients at high cardiovascular risk are however not known. Therefore, we investigated the cardiovascular prognosis in overweight/obese subjects with anemia. A total of 9,687 overweight/obese cardiovascular high-risk patients from the Sibutramine Cardiovascular OUTcomes trial were studied. Patients were stratified after baseline hemoglobin level and followed for the risks of primary event (comprising nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality. Risk estimates (hazard ratios (HR) with 95% confidence intervals (CI)) were calculated using Cox regression models. Anemia was unadjusted associated with increased risk for the primary event, HR 1.73 (CI 1.37-2.18) and HR 2.02 (CI 1.34-3.06) for patients with mild or moderate-to-severe anemia, respectively, compared with patients without anemia. Adjusted for several confounders, anemia remained of prognostic importance. Increased risk of the primary events appeared to be driven by risk of cardiovascular death, adjusted HR 1.82 (CI 1.33-2.51) for mild anemia and adjusted HR 1.65 (CI 0.90-3.04) for moderate-to-severe anemia, and all-cause mortality, adjusted HR 1.50 (CI 1.17-1.93) for mild and adjusted HR 1.61 (CI 1.04-2.51) for moderate-to-severe anemia. While adding serum creatinine to the models, the increased risk of mild anemia was still a significant predictor for mortality (cardiovascular and all-cause), whereas moderate-to-severe anemia was not. For the primary events, anemia was no longer of independent prognostic importance when including serum creatinine. Anemia is associated with an increased risk of long-term adverse cardiovascular events and deaths among overweight/obese cardiovascular high-risk patients. The increased risk appeared to be driven by the risk of cardiovascular death and all-cause mortality, and renal impairments seemed to have a role in the increased risk.

Severe hypocalcaemia and hypophosphataemia following intravenous iron and denosumab: a novel drug interaction.

PubMed

Smyth, B; Ong, S

2016-03-01

We present the case of a 59-year-old woman with chronic kidney disease who suffered severe hypocalcaemia and hypophosphataemia after receiving denosumab and intravenous iron. This potentially life-threatening adverse drug interaction has never been reported before. We propose a mechanism to explain it with reference to the physiological derangements caused by both agents on calcium and phosphate homeostasis. © 2016 Royal Australasian College of Physicians.

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

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.

Neutrophilic dermatitis and immune-mediated haematological disorders in a dog: suspected adverse reaction to carprofen.

PubMed

Mellor, P J; Roulois, A J A; Day, M J; Blacklaws, B A; Knivett, S J; Herrtage, M E

2005-05-01

This report describes the clinical and pathological findings of a suspected idiosyncratic adverse drug reaction in a young dog. The patient presented with sudden onset, severe skin lesions together with episodes of collapse. Investigations revealed a neutrophilic dermatitis with vasculitis, immune-mediated haemolytic anaemia and thrombocytopenia. Similar pathology has been described in human cases of Sweet's syndrome. The chronology of events suggested an adverse drug reaction to carprofen, although two antibiotics had been prescribed within the dog's recent history. Lymphocyte transformation tests were performed and tended to exclude both antibiotics as the cause of the reaction. To the authors' knowledge, lymphocyte transformation tests have not previously been described with regard to drug hypersensitivity assessment in the veterinary literature, and this is the first peer-reviewed case report of neutrophilic dermatitis and vasculitis with immune-mediated haemolytic anaemia and thrombocytopenia occurring as a suspected adverse drug reaction to carprofen in the dog.

Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.

PubMed

Ridpath, Alison; Driver, Cynthia R; Nolan, Michelle L; Karpati, Adam; Kass, Daniel; Paone, Denise; Jakubowski, Andrea; Hoffman, Robert S; Nelson, Lewis S; Kunins, Hillary V

2014-12-19

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.

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.

Evaluation of Unintended Social and Economic Consequences of an Unplanned School Closure in Rural Illinois

ERIC Educational Resources Information Center

Tsai, Victoria; Khan, Nomana M.; Shi, Jianrong; Rainey, Jeanette; Gao, Hongjiang; Zheteyeva, Yenlik

2017-01-01

Background: School closure is one of the primary measures considered during severe influenza pandemics and other emergencies. However, prolonged school closures may cause unintended adverse consequences to schools, students, and their families. A better understanding of these consequences will inform prepandemic planning, and help public health…

Intrauterine Candida albicans infection elicits severe inflammation in fetal sheep

PubMed Central

Payne, Matthew S.; Kemp, Matthew W.; Kallapur, Suhas G.; Kannan, Paranthaman Senthamarai; Saito, Masatoshi; Miura, Yuichiro; Newnham, John P.; Stock, Sarah; Ireland, Demelza J.; Kramer, Boris W.; Jobe, Alan H.

2014-01-01

Background Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesised that intraamniotic C. albicans would cause a vigorous, acute fetal inflammatory response. Methods Sheep carrying singleton pregnancies received single intraamniotic (IA) injections of either saline (control) or 107 CFU C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation. Results Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterised by fetal thrombocytopenia, lymphopenia and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung and the amniotic fluid. Conclusion Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen which can contribute to adverse pregnancy outcomes. PMID:24632681

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.

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.

Case of streptococcal toxic shock syndrome caused by rapidly progressive group A hemolytic streptococcal infection during postoperative chemotherapy for cervical cancer.

PubMed

Nogami, Yuya; Tsuji, Kousuke; Banno, Kouji; Umene, Kiyoko; Katakura, Satomi; Kisu, Iori; Tominaga, Eiichiro; Aoki, Daisuke

2014-01-01

Streptococcal toxic shock syndrome (STSS) is a severe infectious disease caused by group A hemolytic streptococcus (Streptococcus pyogenes). This condition is a serious disease that involves rapidly progressive septic shock. We experienced a case of STSS caused by primary peritonitis during treatment with paclitaxel and cisplatin (TP therapy) as postoperative chemotherapy for cervical cancer. STSS mostly develops after extremity pain, but initial influenza-like symptoms of fever, chill, myalgia and gastrointestinal symptoms may also occur. TP therapy is used to treat many cancers, including gynecological cancer, but may cause adverse reactions of neuropathy and nephrotoxicity and sometimes fever, arthralgia, myalgia, abdominal pain and general malaise. The case reported here indicates that development of STSS can be delayed after chemotherapy and that primary STSS symptoms may be overlooked because they may be viewed as adverse reactions to chemotherapy. To our knowledge, this is the first report of a case of STSS during chemotherapy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

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.

Cardiovascular drugs inducing QT prolongation: facts and evidence.

PubMed

Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

2010-01-01

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

Generalised peripheral oedema associated with amlodipine therapy in two dogs.

PubMed

Creevy, K E; Scuderi, M A; Ellis, A E

2013-11-01

This report details two cases of adverse drug reactions to amlodipine. The first case presented with diffuse peripheral oedema and a history of amlodipine therapy. Haematology, clinical chemistry, endocrine testing, thoracic, abdominal and cardiac imaging revealed no cause for oedema. Amlodipine therapy was discontinued and oedema diminished markedly within 72 hours. The second case presented for bilateral retinal detachments secondary to systemic hypertension. Haematology, clinical chemistry, thoracic and abdominal imaging were unremarkable and amlodipine therapy was begun. Within 72 hours, diffuse peripheral oedema developed that was unresponsive to therapy and the dog was euthanised. Veterinarians should be aware of the potential serious adverse events associated with commonly used drugs; severe, diffuse oedema is a possible adverse drug event in dogs treated with amlodipine. © 2013 British Small Animal Veterinary Association.

Neurological adverse events associated with vaccination.

PubMed

Piyasirisilp, Sucheep; Hemachudha, Thiravat

2002-06-01

Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

[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.

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

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

PubMed

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

2015-03-01

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

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

PubMed Central

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

2015-01-01

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

Is detection of adverse events affected by record review methodology? an evaluation of the "Harvard Medical Practice Study" method and the "Global Trigger Tool".

PubMed

Unbeck, Maria; Schildmeijer, Kristina; Henriksson, Peter; Jürgensen, Urban; Muren, Olav; Nilsson, Lena; Pukk Härenstam, Karin

2013-04-15

There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the "Harvard Medical Practice Study" method and the "Global Trigger Tool" in detecting adverse events in adult orthopaedic inpatients. We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The "Harvard Medical Practice Study" method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the "Global Trigger Tool". Adverse events "causing harm without permanent disability" accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the "Harvard Medical Practice Study" method and the "Global Trigger Tool" was 40.3% and 30.4%, respectively. More adverse events were identified using the "Harvard Medical Practice Study" method than using the "Global Trigger Tool". Differences in review methodology, perception of less severe adverse events and context knowledge may explain the observed difference between two expert review teams in the detection of adverse events.

Adverse Drug Events caused by Serious Medication Administration Errors

PubMed Central

Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G

2013-01-01

OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100 medication doses administered, in a hospital where 6 million doses are administered per year, about 4000 preventable ADEs would be attributable to medication administration errors annually. PMID:22791691

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

PubMed

Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

2015-12-30

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. Copyright © 2016. Published by Elsevier Ltd.

Cutaneous toxicity from epidermal growth factor receptor inhibitors: would a subcutaneous desensitization be helpful? Case report.

PubMed

D'Alessio, Andrea; Cecchini, Sara; Di Mauro, Daniela; Geroli, Luca; Villa, Simonetta; Quadri, Antonello; Resta, Davide; Fortugno, Carmelo

2016-11-11

Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity. Subcutaneous desensitization with increasing concentrations of monoclonal antibodies can induce a tolerance to drug administration and reduce cutaneous adverse effects. To our knowledge, this is the first case in which a reduction or a disappearance of skin toxicity caused by EGFR-Is through subcutaneous desensitization has been achieved. We present cases of 2 Caucasian patients with adenocarcinoma of the colon treated with EGFR-Is who developed severe cutaneous toxicity. A 73-year-old man presented grade 4 skin toxicity of the face and grade 3 skin toxicity of the trunk during treatment with cetuximab. A 68-year-old woman developed G2 rash on the face after the first administration of cetuximab. These patients underwent subcutaneous desensitization with increasing concentrations of EGFR-Is. After this procedure, patients restarted therapy at the optimal dosage with reduction or disappearance of skin toxicity. These cases suggest that by giving rising doses of antibody it is possible to obtain desensitization able to prevent severe cutaneous adverse events in patients treated with EGFR-Is.

A Survey of Logic Formalisms to Support Mishap Analysis

NASA Technical Reports Server (NTRS)

Johnson, Chris; Holloway, C. M.

2003-01-01

Mishap investigations provide important information about adverse events and near miss incidents. They are intended to help avoid any recurrence of previous failures. Over time, they can also yield statistical information about incident frequencies that helps to detect patterns of failure and can validate risk assessments. However, the increasing complexity of many safety critical systems is posing new challenges for mishap analysis. Similarly, the recognition that many failures have complex, systemic causes has helped to widen the scope of many mishap investigations. These two factors have combined to pose new challenges for the analysis of adverse events. A new generation of formal and semi-formal techniques have been proposed to help investigators address these problems. We introduce the term mishap logics to collectively describe these notations that might be applied to support the analysis of mishaps. The proponents of these notations have argued that they can be used to formally prove that certain events created the necessary and sufficient causes for a mishap to occur. These proofs can be used to reduce the bias that is often perceived to effect the interpretation of adverse events. Others have argued that one cannot use logic formalisms to prove causes in the same way that one might prove propositions or theorems. Such mechanisms cannot accurately capture the wealth of inductive, deductive and statistical forms of inference that investigators must use in their analysis of adverse events. This paper provides an overview of these mishap logics. It also identifies several additional classes of logic that might also be used to support mishap analysis.

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.

Misuse and modification of fireworks with fatal injury.

PubMed

Fulcher, James; Luttrell, Harrison; Harvey, Whit; Ward, Michael

2015-06-01

Fireworks deaths are a rare event in the United States with minor injuries comprising most adverse events. We report the case of misuse and modification of a large "mortar" firework with fatal results. In this case, the firework charge was modified with additional fuses and placed into the launcher upside down. The decedent then held the mortar base closely to his chest and lit the modified fuse. The resulting explosion caused severe blunt force trauma with significant hydrostatic shock damage to the heart and liver. This cause highlights the dangers of fireworks, particularly when misused.

Ocular Sarcoidosis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2015-01-01

Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations. PMID:26593141

A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events.

PubMed

Venhuis, Bastiaan; Keizers, Peter; van Riel, Antoinette; de Kaste, Dries

2014-06-01

Food supplements are regularly found to contain pharmacologically active substances. Recently, the food supplement Dexaprine was removed from the Dutch market because it was associated with severe adverse events. Reports to the Dutch Poisons Information Center (DPIC) showed that ingestion of as little as half a tablet caused several cases of nausea, agitation, tachycardia, and palpitations and even one case of cardiac arrest. The remaining tablets of four patients were sent in by different healthcare professionals. Analysis by ultra-performance liquid chromatography quadrupole time of flight mass-spectrometry (UPLC-QTOF-MS) confirmed the presence of synephrine, oxilofrine, deterenol, yohimbine, caffeine, and theophylline. Two more compounds were found which were tentatively identified as β-methyl-β-phenylethylamines. This incident is only the next in a series of similar incidents involving dietary supplements with (undeclared) active substances that are either unsafe or have no known safety profile. Copyright © 2014 John Wiley & Sons, Ltd.

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.

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.

Pembrolizumab-Induced Pancytopenia: A Case Report

PubMed Central

Atwal, Dinesh; Joshi, Krishna P; Ravilla, Rahul; Mahmoud, Fade

2017-01-01

Introduction Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge. Case Presentation A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high-dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy. Discussion In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery. PMID:28746020

Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5-dichlorophenol to adverse outcomes in Lemna minor.

PubMed

Xie, Li; Gomes, Tânia; Solhaug, Knut Asbjørn; Song, You; Tollefsen, Knut Erik

2018-04-01

Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review.

PubMed

Yellapu, Radha K; Mittal, Vivek; Grewal, Priya; Fiel, Mariaisabel; Schiano, Thomas

2011-03-01

Globally, people are struggling with obesity. Many effective, nonconventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful.

Acute liver failure caused by ‘fat burners’ and dietary supplements: A case report and literature review

PubMed Central

Radha Krishna, Y; Mittal, V; Grewal, P; Fiel, MI; Schiano, T

2011-01-01

Globally, people are struggling with obesity. Many effective, non-conventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful. PMID:21499580

Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease.

PubMed

Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

2012-01-01

In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

Agrochemicals against Malaria, Sleeping Sickness, Leishmaniasis and Chagas Disease

PubMed Central

Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

2012-01-01

In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively. PMID:23145187

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

PubMed

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

2017-01-01

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

Acute Generalized Exanthematous Pustulosis Due to Oral Use of Blue Dyes

PubMed Central

Sener, Osman; Kose, Ösman; Safali, Mukerrem

2011-01-01

Acute generalized exanthematous pustulosis is a rare severe pustular cutaneous adverse reaction characterized by a rapid clinical course with typical histological findings. It is accompanied by fever and acute eruption of non-follicular pustules overlying erythrodermic skin. The causative agents are most frequently antibacterial drugs. We present a patient with acute generalized exanthematous pustulosis caused by methylene blue and indigotin dyes. PMID:22016599

Military Hospitalizations among Deployed US Service Members Following Anthrax Vaccination, 1998-2001

DTIC Science & Technology

2006-04-01

be- known severe adverse health effects , excluding mortality and pregnancy-related outcomes , associated with anthrax vaccination. Outcomes were...January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases...talization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax

CIRSE Guidelines on Percutaneous Vertebral Augmentation

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

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Too, Chow Wei, E-mail: spyder55@gmail.com; Koch, Guillaume, E-mail: guillaume.koch@gmail.com

Vertebral compression fracture (VCF) is an important cause of severe debilitating back pain, adversely affecting quality of life, physical function, psychosocial performance, mental health and survival. Different vertebral augmentation procedures (VAPs) are used in order to consolidate the VCFs, relief pain,and whenever posible achieve vertebral body height restoration. In the present review we give the indications, contraindications, safety profile and outcomes of the existing percutaneous VAPs.

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.

Causal beliefs of the public and social acceptance of persons with mental illness: a comparative analysis of schizophrenia, depression and alcohol dependence.

PubMed

Schomerus, G; Matschinger, H; Angermeyer, M C

2014-01-01

There is an ongoing debate whether biological illness explanations improve tolerance towards persons with mental illness or not. Several theoretical models have been proposed to predict the relationship between causal beliefs and social acceptance. This study uses path models to compare different theoretical predictions regarding attitudes towards persons with schizophrenia, depression and alcohol dependence. In a representative population survey in Germany (n = 3642), we elicited agreement with belief in biogenetic causes, current stress and childhood adversities as causes of either disorder as described in an unlabelled case vignette. We further elicited potentially mediating attitudes related to different theories about the consequences of biogenetic causal beliefs (attribution theory: onset responsibility, offset responsibility; genetic essentialism: differentness, dangerousness; genetic optimism: treatability) and social acceptance. For each vignette condition, we calculated a multiple mediator path model containing all variables. Biogenetic beliefs were associated with lower social acceptance in schizophrenia and depression, and with higher acceptance in alcohol dependence. In schizophrenia and depression, perceived differentness and dangerousness mediated the largest indirect effects, the consequences of biogenetic causal explanations thus being in accordance with the predictions of genetic essentialism. Psychosocial causal beliefs had differential effects: belief in current stress as a cause was associated with higher acceptance in schizophrenia, while belief in childhood adversities resulted in lower acceptance of a person with depression. Biological causal explanations seem beneficial in alcohol dependence, but harmful in schizophrenia and depression. The negative correlates of believing in childhood adversities as a cause of depression merit further exploration.

Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life.

PubMed

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

2009-06-01

Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a "high-volume production" chemical with widespread human exposure. In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

Prenatal Exposure to Bisphenol A at Environmentally Relevant Doses Adversely Affects the Murine Female Reproductive Tract Later in Life

PubMed Central

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

2009-01-01

Background Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure. Objectives In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Methods Timed pregnant CD-1 mice were treated on days 9–16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 μg/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Results Ovarian cysts were significantly increased in the 1-μg/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. Conclusions These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation. PMID:19590677

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

PubMed

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

2017-12-22

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

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.

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.

Learning from adverse incidents involving medical devices.

PubMed

Amoore, John; Ingram, Paula

While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms.

Dermatoses secondary to Asian cultural practices.

PubMed

Lilly, Evelyn; Kundu, Roopal V

2012-04-01

Although Asian cultural practices, such as acupuncture and threading, are widely used, there is limited medical literature describing their cutaneous effects and complications. This review briefly describes therapeutic cultural practices (traditional Chinese medicine, acupuncture, cupping, moxibustion, coining, Ayurveda, and aromatherapy) and cosmetic cultural practices (hair oils, henna, bindis, saris, and threading), with particular attention to dermatoses secondary to these practices. Traditional Chinese medicine and Ayurveda may cause heavy metal toxicity, severe cutaneous adverse reactions, and contact dermatitis. Cupping, moxibustion, and coining lead to dermatoses that may be mistaken for abuse by people unfamiliar with the practices. Hair oils may cause contact dermatitis and folliculitis. Paraphenylenediamine in black henna and bindi dyes and adhesives can cause severe allergic contact dermatitis. The drawstring in saris causes frictional irritation, which can lead to tinea corporis, koebnerization, and even squamous cell carcinoma. Threading may cause folliculitis, impetigo, and verrucae. The increasing prevalence of Asian cultural practices, which are performed inside and outside of Asia in this era of globalization, demands that dermatologists be familiar with the secondary dermatoses that may develop. © 2012 The International Society of Dermatology.

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

[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.

Permanent make-up colorants may cause severe skin reactions.

PubMed

Wenzel, Sabrina M; Welzel, Julia; Hafner, Christian; Landthaler, Michael; Bäumler, Wolfgang

2010-10-01

In recent years, cosmetic tattoos [permanent make-up (PMU)] on eyelids, eyebrows and lips have become increasingly popular. However, most colorants are manufactured for non-medical purposes, without any established history of safe use in humans. To investigate severe adverse reactions, such as swelling, burning, and the development of papules, of the lips and the surrounding area in 4 patients who had had at least two PMU procedures on their lips. Adverse skin reactions were examined with patch and prick testing of the colorants. In addition, skin biopsies were taken in the centre of the prick test for histology. One patient declined prick testing. Beauticians tended to use various PMU products, but all contained Pigment Red 181 (CI 73360). All patients tested showed a clear delayed reaction to Pigment Red 181 or the tattoo ink, or both, after prick testing. Histology indicated an allergic reaction. Each lip lesion slowly abated after several months of topical or systemic therapy with steroids in combination with tacrolimus, but none has yet completely resolved. In light of the severe and often therapy-resistant skin reactions, we strongly recommend the regulation and control of the substances used in PMU colorants. © 2010 John Wiley & Sons A/S.

Evolution of Functional Mitral Regurgitation and Prognosis in Medically Managed Heart Failure Patients With Reduced Ejection Fraction.

PubMed

Nasser, Riwa; Van Assche, Lauranne; Vorlat, Anne; Vermeulen, Tom; Van Craenenbroeck, Emeline; Conraads, Viviane; Van der Meiren, Vicky; Shivalkar, Bharati; Van Herck, Paul; Claeys, Marc J

2017-09-01

The purpose of this study was to assess whether medical management may alter the severity of functional mitral regurgitation (FMR) and its prognosis in patients who have heart failure with reduced ejection fraction (HFrEF). FMR in patients who have HFrEF is associated with a worse prognosis. It is uncertain to what extent medical management may alter the severity of FMR and its prognosis. The extent of FMR was assessed at baseline and after a median follow-up period of 50 months in 163 consecutive HFrEF patients (left ventricular ejection fraction <40%). Severe FMR was defined as mitral regurgitation (MR) grade 3-4. All of the patients received the maximal tolerable doses of their heart failure (HF) medications. Major adverse cardiac events were defined as a composite of all-cause death and the need for heart transplantation or hospitalization for HF and/or malignant arrhythmias. A total of 50 (31%) patients had severe MR at baseline. During the follow-up period, 38% of the severe FMR patients showed an improvement to nonsevere FMR (MR grade <3), whereas 18% of the nonsevere FMR patients developed severe FMR despite optimal HF treatment. Cox regression analysis revealed that the presence of sustained severe FMR or worsening of FMR was the most important independent prognostic determinant with an adjusted odds ratio of 2.5 (95% confidence interval: 1.5 to 4.3, major adverse cardiac events 83% vs. 43%). In addition, those patients showed a 13% increase in left ventricular end-diastolic volume index (LVEDVI), whereas the patients with improvement in their severe MR showed a 2% decrease in LVEDVI (p = 0.01). Severe FMR was successfully treated with medication in almost 40% and was associated with prevention of left ventricular adverse remodeling and with an improved long-term prognosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-05-02

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

Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy

PubMed Central

Ingelman-Sundberg, Magnus; Rodriguez-Antona, Cristina

2005-01-01

The majority of phase I- and phase II-dependent drug metabolism is carried out by polymorphic enzymes which can cause abolished, quantitatively or qualitatively decreased or enhanced drug metabolism. Several examples exist where subjects carrying certain alleles do not benefit from drug therapy due to ultrarapid metabolism caused by multiple genes or by induction of gene expression or, alternatively, suffer from adverse effects of the drug treatment due to the presence of defective alleles. It is likely that future predictive genotyping for such enzymes might benefit 15–25% of drug treatments, and thereby allow prevention of adverse drug reactions and causalities, and thus improve the health of a significant fraction of the patients. However, it will take time before this will be a reality within the clinic. We describe some important aspects in the field with emphasis on cytochrome P450 and discuss also polymorphic aspects of foetal expression of CYP3A5 and CYP3A7. PMID:16096104

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.

Correlation Between Capnography and Arterial Carbon Dioxide Before, During, and After Severe Chest Injury in Swine

DTIC Science & Technology

2012-01-01

In addi- tion to securing a patent airway, first responders must attempt to achieve adequate ventilation, as hyperventilation or hypo- ventilation... hyperventilated or hypoventi- lated (n = 890 intubated and n = 2,709 nonintubated) before hospital arrival. Adverse effects of ventilation are especially...perfusion, whereas hypoventila- tion causes decreased oxygen delivery (3, 4). Additional risks associated with hyperventilation include overinflation of

The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences.

PubMed

de Ferranti, Sarah; Mozaffarian, Dariush

2008-06-01

As the prevalence of adiposity soars in both developed and developing nations, appreciation of the close links between obesity and disease increases. The strong relationships between excess adipose tissue and poor health outcomes, including cardiovascular disease, diabetes, and cancer, mandate elucidation of the complex cellular, hormonal, and molecular pathophysiology whereby adiposity initiates and maintains adverse health effects. In this report we review adipocyte metabolism and function in the context of energy imbalance and postprandial nutrient excess, including adipocyte hypertrophy and hyperplasia, adipocyte dysfunction, and other systemic consequences. We also discuss implications for laboratory evaluation and clinical care, including the role of lifestyle modifications. Chronic energy imbalance produces adipocyte hypertrophy and hyperplasia, endoplasmic reticulum stress, and mitochondrial dysfunction. These processes lead to increased intracellular and systemic release of adipokines, free fatty acids, and inflammatory mediators that cause adipocyte dysfunction and induce adverse effects in the liver, pancreatic beta-cells, and skeletal muscle as well as the heart and vascular beds. Several specialized laboratory tests can quantify these processes and predict clinical risk, but translation to the clinical setting is premature. Current and future pharmacologic interventions may target these pathways; modest changes in diet, physical activity, weight, and smoking are likely to have the greatest impact. Adipocyte endoplasmic reticulum and mitochondrial stress, and associated changes in circulating adipokines, free fatty acids, and inflammatory mediators, are central to adverse health effects of adiposity. Future investigation should focus on these pathways and on reversing the adverse lifestyle behaviors that are the fundamental causes of adiposity.

40 CFR 717.15 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.15 Recordkeeping requirements. (a... significant adverse reactions alleged to have been caused by chemical substances or mixtures manufactured or... structure. Records must be retrievable by the alleged cause of the significant adverse reaction, which cause...

40 CFR 717.15 - Recordkeeping requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.15 Recordkeeping requirements. (a... significant adverse reactions alleged to have been caused by chemical substances or mixtures manufactured or... structure. Records must be retrievable by the alleged cause of the significant adverse reaction, which cause...

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study.

PubMed

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F; Gottlieb, Daniel J; Redline, Susan; Punjabi, Naresh M

2016-10-15

Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV 1 and apnea-hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV 1 , all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08-1.13). In contrast, for every 200-ml decrease in FEV 1 , all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04-1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV 1 , 0.004). Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study

PubMed Central

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F.; Gottlieb, Daniel J.; Redline, Susan

2016-01-01

Rationale: Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. Objectives: The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Methods: Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV1 and apnea–hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. Measurements and Main Results: All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV1, all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08–1.13). In contrast, for every 200-ml decrease in FEV1, all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04–1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV1, 0.004). Conclusions: Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB. PMID:27105053

Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents.

PubMed

McWilliam, Vicki L; Koplin, Jennifer J; Field, Michael J; Sasaki, Mari; Dharmage, Shyamali C; Tang, Mimi L K; Sawyer, Susan M; Peters, Rachel L; Allen, Katrina J

2018-03-01

Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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.

Antifungal resistance: current trends and future strategies to combat

PubMed Central

Wiederhold, Nathan P

2017-01-01

Antifungal resistance represents a major clinical challenge to clinicians responsible for treating invasive fungal infections due to the limited arsenal of systemically available antifungal agents. In addition current drugs may be limited by drug–drug interactions and serious adverse effects/toxicities that prevent their prolonged use or dosage escalation. Fluconazole resistance is of particular concern in non-Candida albicans species due to the increased incidence of infections caused by these species in different geographic locations worldwide and the elevated prevalence of resistance to this commonly used azole in many institutions. C. glabrata resistance to the echinocandins has also been documented to be rising in several US institutions, and a higher percentage of these isolates may also be azole resistant. Azole resistance in Aspergillus fumigatus due to clinical and environmental exposure to this class of agents has also been found worldwide, and these isolates can cause invasive infections with high mortality rates. In addition, several species of Aspergillus, and other molds, including Scedosporium and Fusarium species, have reduced susceptibility or pan-resistance to clinically available antifungals. Various investigational antifungals are currently in preclinical or clinical development, including several of them that have the potential to overcome resistance observed against the azoles and the echinocandins. These include agents that also target ergosterol and b-glucan biosynthesis, as well as compounds with novel mechanisms of action that may also overcome the limitations of currently available antifungal classes, including both resistance and adverse effects/toxicity. PMID:28919789

Outbreak of Adverse Reactions Associated with Contaminated Heparin

PubMed Central

Blossom, David B.; Kallen, Alexander J.; Patel, Priti R.; Elward, Alexis; Robinson, Luke; Gao, Ganpan; Langer, Robert; Perkins, Kiran M.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Jones, Marilyn; Schillie, Sarah F.; Shehab, Nadine; Ketterer, Daniel; Venkataraman, Ganesh; Kishimoto, Takashi Kei; Shriver, Zachary; McMahon, Ann W.; Austen, K. Frank; Kozlowski, Steven; Srinivasan, Arjun; Turabelidze, George; Gould, Carolyn V.; Arduino, Matthew J.; Sasisekharan, Ram

2013-01-01

BACKGROUND In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case–control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak. PMID:19052120

Clinical Evidence of Increase in Hair Growth and Decrease in Hair Loss without Adverse Reactions Promoted by the Commercial Lotion ECOHAIR®.

PubMed

Alonso, María Rosario; Anesini, Claudia

2017-01-01

Hair exerts protection, sensory functions, thermoregulation, and sexual attractiveness. Hair loss (alopecia) is caused by several diseases, drug intake, hormone imbalance, stress, and infections (Malassesia furfur). Drugs usually used in alopecia produce irreversible systemic and local side effects. An association of extracts of Coffea arabica and Larrea divaricata (ECOHAIR®) is successfully being commercialized in Argentina for hair growth. The aim of this study was to provide scientific support for the efficacy and innocuousness of ECOHAIR® in patients with noncicatricial alopecia during a 3-month treatment. The efficacy was determined through the assessment of an increase in hair volume, improvement in hair looks, growth of new hair, and a decrease in hair loss by the test of hair count and hair traction. The capacity to decrease the amount of dandruff was also evaluated as well as the adverse local effects caused by the treatment. ECOHAIR® spray improved the overall hair volume and appearance; it increased its thickness, induced hair growth, and decreased hair loss. Besides, no adverse local reactions were observed upon treatment with the product. This study provides scientific support for the clinical use of ECOHAIR® as a treatment to be used in noncicatricial alopecia. © 2017 S. Karger AG, Basel.

Drug-induced gynecomastia.

PubMed

Bowman, John D; Kim, Hyunah; Bustamante, Juan J

2012-12-01

Drugs account for about 20% of gynecomastia cases in men. As a number of factors can alter the estrogen:androgen ratio, several pathophysiologic mechanisms are associated with drugs causing this disorder. Antiandrogens, protease inhibitors, and nucleoside reverse transcriptase inhibitors are the most common drug causes of gynecomastia, whereas first-generation antipsychotics, spironolactone, verapamil, and cimetidine are less common causes. Other drugs have been reported rarely as causes. Treatment may involve switching to an alternative agent or may require surgery or irradiation if the causative agent cannot be discontinued. We reviewed the literature on drug-induced gynecomastia and provided another perspective by reviewing data from the United States Food and Drug Administration's Adverse Event Reporting System. Epidemiologic studies are needed to provide a more accurate description of the frequency of drug-induced gynecomastia. © 2012 Pharmacotherapy Publications, Inc.

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.

PubMed

Balak, Deepak M W; van Doorn, Martijn B A; Arbeit, Robert D; Rijneveld, Rianne; Klaassen, Erica; Sullivan, Tim; Brevard, Julie; Thio, Hok Bing; Prens, Errol P; Burggraaf, Jacobus; Rissmann, Robert

2017-01-01

Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI). IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo. Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs. EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729. Copyright © 2016 Elsevier Inc. All rights reserved.

Severe Acneiform Eruption Induced by Cetuximab (Erbitux®)

PubMed Central

Lee, Jung Eun; Lee, Sang Ju; Lee, Hee Jung; Lee, Ju Hee

2008-01-01

Epidermal growth factor has an important role in the regulation of proliferation and differentiation in epidermal keratinocytes, as well as in the survival, angiogenesis and metastasis of cancer cells. Cetuximab is a chimeric monoclonal antibody selective for the epidermal growth factor receptor that induces a broad range of cellular responses that enhance tumor sensitivity to radiotherapy and chemotherapeutic agents. However, it can cause adverse events in the patient including acneiform eruption, asthenia, abdominal pain and nausea/vomiting. We report a case of severe acneiform eruption induced by cetuximab in a 56-year-old man with colorectal cancer and liver metastases. PMID:18972607

Public health impact of androgens.

PubMed

Kanayama, Gen; Kaufman, Marc J; Pope, Harrison G

2018-06-01

To summarize recent findings regarding the public health impact of androgen abuse. Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease. Withdrawal from androgens after long-term use may produce prolonged and sometimes irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes cause irritability, aggressiveness, and violence, whereas androgen withdrawal may cause depression. However, these psychiatric effects are idiosyncratic, affecting only a minority of users. Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia. Several recent studies have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse musculoskeletal effects. Recent studies have demonstrated marked adverse effects of long-term androgen abuse. As increasing numbers of androgen abusers reach middle age, these effects will likely represent an emerging public health problem.

Use of strong opioids for chronic pain in osteoarthritis: an insight into the Latin American reality.

PubMed

Ruiz Iban, Miguel Angel; Benavides, Javier; Forero, Juan Pablo; Bittelman, Sacha; Martinez, Rafael; Mite, Miguel Angel; Diaz Heredia, Jorge; Ulloa, Sergio; Lizárraga Ferrand, Mauro Marcelo

2018-01-01

Osteoarthritis is the most common cause of arthritis and one of the main causes of chronic pain. Although opioids are frequently employed for chronic pain treatment, their usage for osteoarthritis pain remains controversial due to the associated adverse effects. Most guidelines reserve their use for refractory pain in patients with hip and knee osteoarthritis. The situation is even more complex in Latin America, where the prevalence of insufficient pain treatment is high because of the limited availability and use of strong opioids. Areas covered: In this article we review the epidemiology of osteoarthritis, its socioeconomic burden, its impact as a chronic pain cause and the pharmacological treatment options, giving emphasis to the role of strong opioids, their safety and efficacy, especially in Latin American countries, where restrictions regulate their usage. Expert commentary: Usage of strong opioids is safe and effective in the short-term management of osteoarthritis with moderate to severe pain, when other pharmacological treatments are inadequate and surgery is contraindicated, provided their use adheres to existing guidelines. Educational programs for patients and physicians and further research on treating chronic pain with opioids should be implemented to reduce adverse effects and improve care quality.

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

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

PubMed Central

Chen, Chong; Zhang, Shu-Ye; Zhang, Dan-Dan; Li, Xin-Yan; Zhang, Yu-Ling; Li, Wei-Xia; Yan, Jing-Jing; Wang, Min; Xun, Jing-Na; Lu, Chuan; Ling, Yun; Huang, Yu-Xian; Chen, Liang

2016-01-01

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV). METHODS This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes. RESULTS The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome. PMID:28058019

[Application of root cause analysis in healthcare].

PubMed

Hsu, Tsung-Fu

2007-12-01

The main purpose of this study was to explore various aspects of root cause analysis (RCA), including its definition, rationale concept, main objective, implementation procedures, most common analysis methodology (fault tree analysis, FTA), and advantages and methodologic limitations in regard to healthcare. Several adverse events that occurred at a certain hospital were also analyzed by the author using FTA as part of this study. RCA is a process employed to identify basic and contributing causal factors underlying performance variations associated with adverse events. The rationale concept of RCA offers a systemic approach to improving patient safety that does not assign blame or liability to individuals. The four-step process involved in conducting an RCA includes: RCA preparation, proximate cause identification, root cause identification, and recommendation generation and implementation. FTA is a logical, structured process that can help identify potential causes of system failure before actual failures occur. Some advantages and significant methodologic limitations of RCA were discussed. Finally, we emphasized that errors stem principally from faults attributable to system design, practice guidelines, work conditions, and other human factors, which induce health professionals to make negligence or mistakes with regard to healthcare. We must explore the root causes of medical errors to eliminate potential RCA system failure factors. Also, a systemic approach is needed to resolve medical errors and move beyond a current culture centered on assigning fault to individuals. In constructing a real environment of patient-centered safety healthcare, we can help encourage clients to accept state-of-the-art healthcare services.

Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity.

PubMed

Roberts, Christine L; Ford, Jane B; Algert, Charles S; Bell, Jane C; Simpson, Judy M; Morris, Jonathan M

2009-02-25

Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3-5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising PPH rates would halt the increase in adverse maternal outcomes.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

PubMed Central

Chen, Chun-Bing; Wu, Ming-Ying; Ng, Chau Yee; Lu, Chun-Wei; Wu, Jennifer; Kao, Pei-Han; Yang, Chan-Keng; Peng, Meng-Ting; Huang, Chen-Yang; Chang, Wen-Cheng; Hui, Rosaline Chung-Yee; Yang, Chih-Hsun; Yang, Shun-Fa; Chung, Wen-Hung; Su, Shih-Chi

2018-01-01

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management. PMID:29844705

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Adverse childhood experiences: towards a clear conceptual meaning.

PubMed

Kalmakis, Karen A; Chandler, Genevieve E

2014-07-01

To report an analysis of the concept of adverse childhood experiences. Adverse childhood experiences have been associated with negative physical and psychological health outcomes, but this phenomenon lacks the clear, consistent meaning necessary for use in nursing research, theory development and practice. Concept clarification. The literature search was not limited a priori by date and included publications with abstracts in English from PubMed, CINAHL, PsychINFO and Social Abstracts. The search retrieved 128 articles published from 1970-2013. The search term 'adverse childhood experiences' was used, with similar terms permitted. A snowball approach was used to expand the search to relevant literature. The articles were read and analysed following Norris's five steps for concept clarification to refine, elucidate and operationally define the concept and the context in which it occurred. Adverse childhood experiences were defined operationally as childhood events, varying in severity and often chronic, occurring in a child's family or social environment that cause harm or distress, thereby disrupting the child's physical or psychological health and development. This concept clarification should raise awareness and understanding of the diverse nature and shared characteristics of adverse childhood experiences that are believed to influence the health of individuals as they age. This clarified concept will help expand research on health consequences of adverse childhood experiences and interventions to improve health. We recommend promoting a model of primary care that pays attention to the social and familial influences on the health of individuals worldwide. © 2013 John Wiley & Sons Ltd.

Antibacterial treatment of bacterial vaginosis: current and emerging therapies

PubMed Central

Menard, Jean-Pierre

2011-01-01

Bacterial vaginosis is a common cause of malodorous vaginal discharge. It is also associated with sexually transmitted infections and adverse pregnancy outcomes. The magnitude of the gynecological and obstetrical consequences has stimulated therapeutic research and led to the testing of several therapies. The objective of this work is to present the currently available therapeutic strategies for the treatment of bacterial vaginosis and associated recommendations, and discuss the emerging therapies. PMID:21976983

Incidence and Predictors of Long-Term Adverse Outcomes in Patients with Rheumatic Mitral Stenosis in Sinus Rhythm.

PubMed

Nachom, Patsadee; Ratanasit, Nithima

2016-04-01

Rheumatic fever and rheumatic heart disease remain important health problems in developing countries. Mitral stenosis (MS) is the most common form of rheumatic heart disease. The aim of this study was to investigate incidence and echocardiographic predictors of long-term adverse outcomes in patients with rheumatic mitral stenosis in sinus rhythm. We retrospectively reviewed medical records of patients diagnosed with isolated rheumatic MS of any severity at Siriraj Hospital between 1996 and 2013. Demographic data, echocardiographic data, and long-term adverse outcomes were collected. Long-term adverse outcomes included all-cause mortality, hospitalization due to heart failure, new-onset atrial fibrillation, and/or embolic stroke during follow-up. One hundred eighty five patients (aged 41.9 ± 13.2 years, 81.1% female) were included during the median follow-up period of 12.6 years (95% CI: 11.2-14.0). MS was classified as mild, moderate, and severe in 8.6%, 2 7.6%, and 63.8% of patients, respectively. Average mitral valve score was 8.25 ± 1.5. Most patients (61.6%) underwent percutaneous balloon mitral valvulotomy. Incidence of long-term adverse outcome was 43.2% (95% CI: 36.0-50.7%) and included mortality in two patients (1.1%, 95% CI: 0.13-3.9%), hospitalization due to heart failure in 20 patients (10.8%, 95% CI: 6.7-16.2%), new-onset atrial fibrillation in 71 patients (38.4%, 95% CI: 31.3-45.8%), and embolic stroke in 14 patients (7.6%, 95% CI: 4.2-12.4%). Echocardiographic parameters associated with long-term adverse outcomes were left atrial dimension greater than 50 mm (HR 2.61, 95% CI: 1.08-6.30; p = 0.03) and left ventricular end-systolic dimension less than 28 mm (HR 3.06, 95% CI: 1.25-7.49; p = 0.01). Long-term adverse outcomes are common in patients with rheumatic MS in sinus rhythm. Long-term adverse outcomes were found to correlate with left atrial dimension and left ventricular end-systolic dimension.

Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity).

PubMed

Laron, Zvi

2008-03-01

Laron syndrome (LS, congenital primary GH insensitivity) is caused by deletions or mutations in the GH receptor gene, resulting in an inability to generate insulin-like growth factor-I (IGF-I). If untreated, the deficiency of IGF-I results in severe dwarfism, as well as skeletal and muscular underdevelopment. The only treatment is the daily administration of recombinant IGF-I. This review summarizes the present experience by several groups worldwide. The main conclusions are: A. The one or two injections regimen result in the same growth velocity; B. The growth velocity obtained with IGF-I administration is smaller than that observed with hGH in children with congenital isolated GH deficiency; C. Overdosage of IGF-I causes a series of adverse effects which can be avoided by carefully monitoring the serum IGF-I and GH levels.

Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis.

PubMed

Egger, M; Davey Smith, G; Stettler, C; Diem, P

1997-11-01

While the benefits of intensified insulin treatment in insulin-dependent (Type 1) diabetes mellitus (IDDM) are well recognized, the risks have not been comprehensively characterized. We examined the risk of severe hypoglycaemia, ketoacidosis, and death in a meta-analysis of randomized controlled trials. The MEDLINE database, reference lists, and specialist journals were searched electronically or by hand to identify relevant studies with at least 6 months of follow-up and the monitoring of glycaemia by glycosylated haemoglobin measurements. Logistic regression was used for calculation of combined odds ratios and 95% confidence intervals (95% CI). The influence of covariates was examined by including covariate-by-treatment interaction terms. Methodological study quality was assessed and sensitivity analyses were performed. Fourteen trials were identified. These contributed 16 comparisons with 1028 patients allocated to intensified and 1039 allocated to conventional treatment. A total of 846 patients suffered at least one episode of severe hypoglycaemia, 175 patients experienced ketoacidosis and 26 patients died. The combined odds ratio (95% CI) for hypoglycaemia was 2.99 (2.45-3.64), for ketoacidosis 1.74 (1.27-2.38) and for death from all causes 1.40 (0.65-3.01). The risk of severe hypoglycaemia was determined by the degree of normalization of glycaemia achieved (p=0.005 for interaction term), with the results from the Diabetes Control and Complications Trial (DCCT) in line with the other trials. Ketoacidosis risk depended on the type of intensified treatment used. Odds ratios (95% CI) were 7.20 (2.95-17.58) for exclusive use of pumps, 1.13 (0.15-8.35) for multiple daily injections and 1.28 (0.90-1.83) for trials offering a choice between the two (p = 0.004 for interaction). Mortality was significantly (p = 0.007) increased for causes potentially associated with acute complications (7 vs 0 deaths, 5 deaths attributed to ketoacidosis, and 2 sudden deaths), and non-significantly (p = 0.16) decreased for macrovascular causes (3 vs 8 deaths). We conclude that there is a substantial risk of severe adverse effects associated with intensified insulin treatment. Mortality from acute metabolic causes is increased; however, this is largely counterbalanced by a reduction in cardiovascular mortality. The excess of severe hypoglycemia in the DCCT is not exceptional. Multiple daily injection schemes may be safer than treatment with insulin pumps.

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

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

2017-01-01

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

Frequency, Risk Factors, and Adverse Fetomaternal Outcomes of Placenta Previa in Northern Tanzania

PubMed Central

Senkoro, Elizabeth Eliet; Mwanamsangu, Amasha H.; Chuwa, Fransisca Seraphin; Msuya, Sia Emmanuel; Mnali, Oresta Peter

2017-01-01

Background and Objective. Placenta previa (PP) is a potential risk factor for obstetric hemorrhage, which is a major cause of fetomaternal morbidity and mortality in developing countries. This study aimed to determine frequency, risk factors, and adverse fetomaternal outcomes of placenta previa in Northern Tanzania. Methodology. A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre birth registry spanning 2000 to 2015. All women who gave birth to singleton infants were studied. Adjusted odds ratios (ORs) with 95% confidence intervals for risk factors and adverse fetomaternal outcomes associated with PP were estimated in multivariable logistic regression models. Result. A total of 47,686 singleton deliveries were analyzed. Of these, the frequency of PP was 0.6%. Notable significant risk factors for PP included gynecological diseases, alcohol consumption during pregnancy, malpresentation, and gravidity ≥5. Adverse maternal outcomes were postpartum haemorrhage, antepartum haemorrhage, and Caesarean delivery. PP increased odds of fetal Malpresentation and early neonatal death. Conclusion. The prevalence of PP was comparable to that found in past research. Multiple independent risk factors were identified. PP was found to have associations with several adverse fetomaternal outcomes. Early identification of women at risk of PP may help clinicians prevent such complications. PMID:28321338

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.

28 CFR 2.214 - Probable cause hearing and determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... adverse witnesses (i.e., witnesses who have given information upon which revocation may be based) at a... confrontation. Whenever a probable cause hearing is postponed to secure the appearance of adverse witnesses (or...

Herbal Medicine in Mexico: A Cause of Hepatotoxicity. A Critical Review

PubMed Central

Valdivia-Correa, Bárbara; Gómez-Gutiérrez, Cristina; Uribe, Misael; Méndez-Sánchez, Nahum

2016-01-01

In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products. PMID:26891292

Herbal Medicine in Mexico: A Cause of Hepatotoxicity. A Critical Review.

PubMed

Valdivia-Correa, Bárbara; Gómez-Gutiérrez, Cristina; Uribe, Misael; Méndez-Sánchez, Nahum

2016-02-15

In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products.

Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation.

PubMed

Zand, Ladan; Muriithi, Angela; Nelsen, Eric; Franco, Pablo M; Greene, Eddie L; Qian, Qi; El-Zoghby, Ziad M

2012-12-01

Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients.

PubMed

Jähn, Johanna; Caliebe, Almuth; von Spiczak, Sarah; Boor, Rainer; Stefanova, Irina; Stephani, Ulrich; Helbig, Ingo; Muhle, Hiltrud

2013-07-01

CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years. All 4 patients had epilepsy starting with focal seizures in the first 3 months of life, evolving to epileptic spasms between the ages of 2 and 6 years and later on to tonic seizures. In 3 patients, epilepsy was resistant to antiepileptic therapy. Although there was no common EEG pattern in all patients, late hypsarrhythmia until the age of 9 years was observed in 2 patients. CDKL5-related epileptic encephalopathies are a group of refractory seizure disorders starting in early infancy. The phenomenon of late hypsarrhythmia may help define a subgroup of patients with severe and adverse outcomes.

Treatment of severe mitral regurgitation caused by lesions in both leaflets using multiple mitral valve plasty techniques in a small dog

PubMed Central

Yokoyama, Satoko; Kanemoto, Isamu; Mihara, Kippei; Ando, Takanori; Kawase, Koudai; Sahashi, Yasuaki; Iguchi, Kazuhito

2017-01-01

Mitral valve plasty (MVP) is preferred over mitral valve replacement (MVR) for mitral regurgitation in humans because of its favorable effect on quality of life. In small dogs, it is difficult to repair multiple lesions in both leaflets using MVP. Herein, we report a case of severe mitral regurgitation caused by multiple severe lesions in the posterior leaflet (PL) in a mixed Chihuahua. Initially, we had planned MVR with an artificial valve. However, MVP combined with artificial chordal reconstruction of both leaflets, semicircular suture annuloplasty, and valvuloplasty using a newly devised direct scallop suture for the PL was attempted in this dog. The dog recovered well and showed no adverse cardiac signs, surviving two major operations. The dog died 4 years and 10 months after the MVP due to non-cardiovascular disease. Our additional technique of using a direct scallop suture seemed useful for PL repair involving multiple scallops in a small dog. PMID:29201662

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.

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

PubMed Central

Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J.

2017-01-01

ABSTRACT The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. PMID:28743813

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.

Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

PubMed Central

Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

2014-01-01

Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

Severe hypertriglyceridaemia during therapy for childhood acute lymphoblastic leukaemia.

PubMed

Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B; Chemaitilly, Wassim; Sandlund, John T; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V; Jeha, Sima; Metzger, Monika L

2014-10-01

Asparaginase and steroids can cause hypertriglyceridaemia in children with acute lymphoblastic leukaemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridaemia (>1000mg/dL) during ALL therapy. Fasting lipid profiles were obtained prospectively at four time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridaemia were extracted retrospectively. Eighteen of 257 (7%) patients developed severe hypertriglyceridaemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridaemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridaemia had a 2.5-3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistically significant. Of the 30 episodes of severe hypertriglyceridaemia in 18 patients, seven were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalised after completion of ALL therapy in all 12 patients with available measurements. Asparaginase- and steroid-induced transient hypertriglyceridaemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridaemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Adverse pregnancy outcomes after Assisted Reproduction Technology in women with endometriosis].

PubMed

Carassou-Maillan, A; Pouly, J-L; Mulliez, A; Dejou-Bouillet, L; Gremeau, A-S; Brugnon, F; Janny, L; Canis, M

2014-04-01

While association between endometriosis and infertility is well established, there are few studies about the impact of endometriosis on adverse pregnancy outcomes. The aim of this study was to determine the effect of endometriosis on obstetric outcomes and whether the severity of the disease had an influence on these. We performed a retrospective study to investigate the obstetric outcomes of a population of 1204 subfertile women, including 258 with endometriosis, who obtained, thanks to assisted reproduction technology, a singleton pregnancy evolving beyond embryonic stage. Two analyzes were performed. The first compared women with endometriosis to women with other causes of infertility. The second observed adverse pregnancy outcomes according to AFS-R stages of endometriosis. The overall rate of live birth children was 95.8%. In case of endometriosis, there was a significant increase of the incidence of preterm delivery, especially before 32 weeks amenorrhea (6.2% vs 3.1% in the group "without endometriosis", P = 0.03), antenatal bleeding (5.3% vs 2.2%, P = 0.01) and placenta previa (4.9% vs 0.9%, P < 0.0001). The incidence of gestational diabetes was significantly decreased (0.4% vs 2.7%, P = 0.04). There was no correlation between endometriosis and cesarean section or preeclampsia, or between the AFS-R stage and adverse pregnancy outcomes. Endometriosis is a factor of obstetrical risk, independently of the infertility it causes. The AFS-R score does not seem to be representative of obstetric outcomes beyond first trimester of pregnancy for women with endometriosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

An observational study of the frequency, severity, and etiology of failures in postoperative care after major elective general surgery.

PubMed

Symons, Nicholas R A; Almoudaris, Alex M; Nagpal, Kamal; Vincent, Charles A; Moorthy, Krishna

2013-01-01

To investigate the nature of process failures in postoperative care, to assess their frequency and preventability, and to explore their relationship to adverse events. Adverse events are common and are frequently caused by failures in the process of care. These processes are often evaluated independently using clinical audit. There is little understanding of process failures in terms of their overall frequency, relative risk, and cumulative effect on the surgical patient. Patients were observed daily from the first postoperative day until discharge by an independent surgeon. Field notes on the circumstances surrounding any nonroutine or atypical event were recorded. Field notes were assessed by 2 surgeons to identify failures in the process of care. Preventability, the degree of harm caused to the patient, and the underlying etiology of process failures were evaluated by 2 independent surgeons. Fifty patients undergoing major elective general surgery were observed for a total of 659 days of postoperative care. A total of 256 process failures were identified, of which 85% were preventable and 51% directly led to patient harm. Process failures occurred in all aspects of care, the most frequent being medication prescribing and administration, management of lines, tubes, and drains, and pain control interventions. Process failures accounted for 57% of all preventable adverse events. Communication failures and delays were the main etiologies, leading to 54% of process failures. Process failures are common in postoperative care, are highly preventable, and frequently cause harm to patients. Interventions to prevent process failures will improve the reliability of surgical postoperative care and have the potential to reduce hospital stay.

A continuous GRASP to determine the relationship between drugs and adverse reactions

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

Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.

2007-11-05

Adverse drag reactions (ADRs) are estimated to be one of the leading causes of death. Many national and international agencies have set up databases of ADR reports for the express purpose of determining the relationship between drugs and adverse reactions that they cause. We formulate the drug-reaction relationship problem as a continuous optimization problem and utilize C-GRASP, a new continuous global optimization heuristic, to approximately determine the relationship between drugs and adverse reactions. Our approach is compared against others in the literature and is shown to find better solutions.

Damage Characterization Method for Structural Health Management Using Reduced Number of Sensor Inputs

NASA Technical Reports Server (NTRS)

Krishnamurthy, T.; Hochhalter, Jacob D.; Gallegos, Adam M.

2012-01-01

The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage (cracks) due to fatigue and low velocity foreign impacts that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage in critical structural components is highly important in developing efficient structural health management systems.

[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.

Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

PubMed

Badovinac, Sonja; Korsic, Marta; Zarkovic, Kamelija; Mursic, Davorka; Roglic, Mihovil; Jakopovic, Marko; Samarzija, Miroslav

2018-03-01

Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities. During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism. Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

Damage Characterization Using the Extended Finite Element Method for Structural Health Management

NASA Technical Reports Server (NTRS)

Krishnamurthy, Thiagarajan; Gallegos, Adam M.

2011-01-01

The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign impact that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage/cracks in critical structural components is highly important in developing efficient structural health management systems.

Vaccine chronicle in Japan.

PubMed

Nakayama, Tetsuo

2013-10-01

The concept of immunization was started in Japan in 1849 when Jenner's cowpox vaccine seed was introduced, and the current immunization law was stipulated in 1948. There have been two turning points for amendments to the immunization law: the compensation remedy for vaccine-associated adverse events in 1976, and the concept of private vaccination in 1994. In 1992, the regional Court of Tokyo, not the Supreme Court, decided the governmental responsibility on vaccine-associated adverse events, which caused the stagnation of vaccine development. In 2010, many universal vaccines became available as the recommended vaccines, but several vaccines, including mumps, zoster, hepatitis B, and rota vaccines, are still voluntary vaccines, not universal routine applications. In this report, immunization strategies and vaccine development are reviewed for each vaccine item and future vaccine concerns are discussed.

Identifying causes of adverse events detected by an automated trigger tool through in-depth analysis.

PubMed

Muething, S E; Conway, P H; Kloppenborg, E; Lesko, A; Schoettker, P J; Seid, M; Kotagal, U

2010-10-01

To describe how in-depth analysis of adverse events can reveal underlying causes. Triggers for adverse events were developed using the hospital's computerised medical record (naloxone for opiate-related oversedation and administration of a glucose bolus while on insulin for insulin-related hypoglycaemia). Triggers were identified daily. Based on information from the medical record and interviews, a subject expert determined if an adverse drug event had occurred and then conducted a real-time analysis to identify event characteristics. Expert groups, consisting of frontline staff and specialist physicians, examined event characteristics and determined the apparent cause. 30 insulin-related hypoglycaemia events and 34 opiate-related oversedation events were identified by the triggers over 16 and 21 months, respectively. In the opinion of the experts, patients receiving continuous-infusion insulin and those receiving dextrose only via parenteral nutrition were at increased risk for insulin-related hypoglycaemia. Lack of standardisation in insulin-dosing decisions and variation regarding when and how much to adjust insulin doses in response to changing glucose levels were identified as common causes of the adverse events. Opiate-related oversedation events often occurred within 48 h of surgery. Variation in pain management in the operating room and post-anaesthesia care unit was identified by the experts as potential causes. Variations in practice, multiple services writing orders, multidrug regimens and variations in interpretation of patient assessments were also noted as potential contributing causes. Identification of adverse drug events through an automated trigger system, supplemented by in-depth analysis, can help identify targets for intervention and improvement.

Hantavirus infection: a global zoonotic challenge.

PubMed

Jiang, Hong; Zheng, Xuyang; Wang, Limei; Du, Hong; Wang, Pingzhong; Bai, Xuefan

2017-02-01

Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.

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.

Adverse weather conditions and fatal motor vehicle crashes in the United States, 1994-2012.

PubMed

Saha, Shubhayu; Schramm, Paul; Nolan, Amanda; Hess, Jeremy

2016-11-08

Motor vehicle crashes are a leading cause of injury mortality. Adverse weather and road conditions have the potential to affect the likelihood of motor vehicle fatalities through several pathways. However, there remains a dearth of assessments associating adverse weather conditions to fatal crashes in the United States. We assessed trends in motor vehicle fatalities associated with adverse weather and present spatial variation in fatality rates by state. We analyzed the Fatality Analysis Reporting System (FARS) datasets from 1994 to 2012 produced by the National Highway Traffic Safety Administration (NHTSA) that contains reported weather information for each fatal crash. For each year, we estimated the fatal crashes that were associated with adverse weather conditions. We stratified these fatalities by months to examine seasonal patterns. We calculated state-specific rates using annual vehicle miles traveled data for all fatalities and for those related to adverse weather to examine spatial variations in fatality rates. To investigate the role of adverse weather as an independent risk factor for fatal crashes, we calculated odds ratios for known risk factors (e.g., alcohol and drug use, no restraint use, poor driving records, poor light conditions, highway driving) to be reported along with adverse weather. Total and adverse weather-related fatalities decreased over 1994-2012. Adverse weather-related fatalities constituted about 16 % of total fatalities on average over the study period. On average, 65 % of adverse weather-related fatalities happened between November and April, with rain/wet conditions more frequently reported than snow/icy conditions. The spatial distribution of fatalities associated with adverse weather by state was different than the distribution of total fatalities. Involvement of alcohol or drugs, no restraint use, and speeding were less likely to co-occur with fatalities during adverse weather conditions. While adverse weather is reported for a large number of motor vehicle fatalities for the US, the type of adverse weather and the rate of associated fatality vary geographically. These fatalities may be addressed and potentially prevented by modifying speed limits during inclement weather, improving road surfacing, ice and snow removal, and providing transit alternatives, but the impact of potential interventions requires further research.

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.

Influence of the Circadian System on Disease Severity

PubMed Central

Litinski, Mikhail; Scheer, Frank AJL; Shea, Steven A

2009-01-01

Synopsis The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy. PMID:20161149

Herbal products and the liver: a review of adverse effects and mechanisms.

PubMed

Seeff, Leonard B; Bonkovsky, Herbert L; Navarro, Victor J; Wang, Guqi

2015-03-01

Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses. Recently, their use in Western countries has grown significantly, rivaling that of prescription medications. Currently, herbal products are used mainly for weight loss and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases. Many people believe that because they are natural, they must be effective and safe; however, these beliefs are erroneous. Few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary. Moreover, current highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant. Herbal products are no safer than conventional drugs and have caused liver injury severe enough to require transplantation or cause death. Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents. We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Flow visualization of mast-mounted-sight/main rotor aerodynamic interactions

NASA Technical Reports Server (NTRS)

Ghee, Terence A.; Kelley, Henry L.

1993-01-01

Flow visualization tests were conducted on a 27 percent-scale AH-64 attack helicopter model fitted with various mast-mounted-sight configurations in an attempt to identify the cause of adverse vibration encountered during full-scale flight tests of an Apache/Longbow configuration. The tests were conducted at the NASA Langley Research Center in the 14- by 22-Foot Subsonic Tunnel. A symmetric and an asymmetric mast-mounted-sight oriented at several skew angles were tested at forward and rearward flight speeds of 30 and 45 knots. A laser light sheet seeded with vaporized propylene glycol was used to visualize the wake of the sight in planes parallel and perpendicular to the freestream flow. Analysis of the flow visualization data identified the frequency of the wake shed from the sight, the angle-of-attack at the sight, and the location where the sight wake crossed the rotor plane. Differences in wake structure were observed between the various sight configurations and slew angles. Postulations into the cause of the adverse vibration found in flight test are given along with considerations for future tests.

Endoplasmic Reticulum Stress Caused by Lipoprotein Accumulation Suppresses Immunity against Bacterial Pathogens and Contributes to Immunosenescence

PubMed Central

Singh, Jogender

2017-01-01

ABSTRACT The unfolded protein response (UPR) is a stress response pathway that is activated upon increased unfolded and/or misfolded proteins in the endoplasmic reticulum (ER), and enhanced ER stress response prolongs life span and improves immunity. However, the mechanism by which ER stress affects immunity remains poorly understood. Using the nematode Caenorhabditis elegans, we show that mutations in the lipoproteins vitellogenins, which are homologs of human apolipoprotein B-100, resulted in upregulation of the UPR. Lipoprotein accumulation in the intestine adversely affects the immune response and the life span of the organism, suggesting that it could be a contributing factor to immunosenescence. We show that lipoprotein accumulation inhibited the expression of several immune genes encoding proteins secreted by the intestinal cells in an IRE-1-independent manner. Our studies provide a mechanistic explanation for adverse effects caused by protein aggregation and ER stress on immunity and highlight the role of an IRE-1-independent pathway in the suppression of the expression of genes encoding secreted proteins. PMID:28559483

The increasing relevance of biofilms in common dermatological conditions.

PubMed

Kravvas, G; Veitch, D; Al-Niaimi, F

2018-03-01

Biofilms are diverse groups of microorganisms encased in a self-produced matrix that offers protection against unfavorable conditions and antibiotics. We performed a literature search using the MEDLINE electronic database. Only original articles published in English were considered for review. Biofilms have been implicated in the pathogenesis of acne, eczema, hidradenitis suppurativa, onychomycosis, miliaria, and impetigo. Adverse dermal-filler reactions are also linked to biofilms. Strict aseptic technique and prophylactic antibiotics are recommended in order to avoid such complications. Finally, biofilms are implicated in wounds, mainly chronic and diabetic, where they impede healing and cause recurrent infections. Several novel anti-biofilm agents and wound debridement have been shown to be beneficial. Biofilms are a significant cause of disease with wide implications in the field of dermatology. Several novel treatments have been found to be effective against biofilms, depending on the underlying microbes and type of disease.

Neutropenia during HIV Infection: Adverse Consequences and Remedies

PubMed Central

Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

2016-01-01

Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update.

PubMed

Nagai, Hiroki; Muto, Manabu

2018-06-01

Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin's lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.

Real‐World Multicenter Registry of Patients with Severe Coronary Artery Calcification Undergoing Orbital Atherectomy

PubMed Central

Shlofmitz, Evan; Kaplan, Barry; Alexandru, Dragos; Meraj, Perwaiz; Shlofmitz, Richard

2016-01-01

Objectives We evaluated the safety and efficacy of orbital atherectomy in real‐world patients with severe coronary artery calcification (CAC). Background The presence of severe CAC increases the complexity of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. Atherectomy may be an indispensable tool for uncrossable or undilatable lesions by modifying severe CAC. Although the ORBIT I and II trials report that orbital atherectomy was safe and effective for the treatment of severe CAC, patients with kidney disease, recent myocardial infarction, long diffuse disease, severe left ventricular dysfunction, and unprotected left main disease were excluded. Methods This retrospective study included 458 consecutive patients with severe CAC who underwent orbital atherectomy followed by stenting from October 2013 to December 2015 at 3 centers. Results The primary endpoint of major adverse cardiac and cerebrovascular events at 30 days was 1.7%. Low rates of 30‐day all‐cause mortality (1.3%), myocardial infarction (1.1%), target vessel revascularization (0%), stroke (0.2%), and stent thrombosis (0.9%) were observed. Angiographic complications were low: perforation was 0.7%, dissection 0.9%, and no‐reflow 0.7%. Emergency coronary artery bypass graft surgery was performed in 0.2% of patients. Conclusion In the largest real‐world study of patients who underwent orbital atherectomy, including high‐risk patients who were not surgical candidates as well as those with very complex coronary anatomy, acute and short‐term adverse clinical event rates were low. A randomized clinical trial is needed to identify the ideal treatment strategy for patients with severe CAC. PMID:27358246

Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study.

PubMed

Courjon, J; Pulcini, C; Cua, E; Risso, K; Guillouet, F; Bernard, E; Roger, P-M

2013-12-01

Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.

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

PubMed

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

2011-08-01

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

Pulmonary vasodilation in acute and chronic heart failure: empiricism and evidence.

PubMed

Guglin, Maya

2011-09-01

Pulmonary hypertension in heart failure is associated with exercise intolerance and adverse outcomes. With the availability of multiple drugs that cause pulmonary vasodilation and decrease pulmonary arterial pressure, pulmonary hypertension becomes an attractive therapeutic target. Out of several classes of medications, oral phosphodiesterase inhibitors emerge as the most promising in terms of symptomatic improvement, hemodynamic benefits, reverse cardiac remodeling, and functional capacity. Future trials will show whether the use of these drugs translates to decreased morbidity and mortality in heart failure.

Acute bilateral parotitis occurring during venlafaxine titration in an adolescent female with major depression.

PubMed

Bonnet, U; Khalil-Boutros, Y

2014-01-01

Parotitis is a fairly uncommon adverse drug reaction of psychopharmacological treatment. Here, we report on an acute bilateral parotitis, which was associated with titration of venlafaxine in a 20-year-old female suffering from a severe depressive episode. The parotitis recovered quickly with oral penicillin and was most likely caused by bacteria assumed to spread from oral flora into Stensen's duct as a complication of pronounced venlafaxine-induced xerostomia. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of eslicarbazepine acetate and oxcarbazepine on cognition and psychomotor function in healthy volunteers.

PubMed

Milovan, Denise; Almeida, Luis; Romach, Myroslava K; Nunes, Teresa; Rocha, José Francisco; Sokowloska, Marta; Sellers, Edward M; Soares-da-Silva, Patrício

2010-08-01

The results of two single-blind studies conducted to evaluate the cognitive and psychomotor effects of eslicarbazepine acetate and oxcarbazepine following single and repeated administration in healthy volunteers are reported. The cognitive and psychomotor evaluation consisted of several computerized and paper-and-pencil measures. Eslicarbazepine acetate and oxcarbazepine had similar overall cognitive profiles and did not cause clinically relevant cognitive impairment. The incidence of adverse events was lower with eslicarbazepine acetate than with oxcarbazepine. Copyright 2010. Published by Elsevier Inc.

The role of adequate reference materials in density measurements in hemodialysis

NASA Astrophysics Data System (ADS)

Furtado, A.; Moutinho, J.; Moura, S.; Oliveira, F.; Filipe, E.

2015-02-01

In hemodialysis, oscillation-type density meters are used to measure the density of the acid component of the dialysate solutions used in the treatment of kidney patients. An incorrect density determination of this solution used in hemodialysis treatments can cause several and adverse events to patients. Therefore, despite the Fresenius Medical Care (FME) tight control of the density meters calibration results, this study shows the benefits of mimic the matrix usually measured to produce suitable reference materials for the density meter calibrations.

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue and represent a significant burden to patients, healthcare providers, and the pharmaceutical industry. • This review details the current state of the art in biomarkers of ADRs (both genetic and circulating). There is still significant variability in patient response which cannot be explained by current knowledge of genetic risk factors for ADRs; however, we discussed how specific advances in genomics have the potential to yield better and more predictive models. • Many current clinically utilized circulating biomarkers of tissue injury are valid biomarkers for a number of ADRs. However, they often give little insight into the specific cell or tissue subtype which may be affected. Emerging circulating biomarkers with potential to provide greater information on the etiology/pathophysiology of ADRs are described.

Obstetric acute renal failure 1956-1987.

PubMed

Turney, J H; Ellis, C M; Parsons, F M

1989-06-01

A total of 142 women with severe acute renal failure (ARF) resulting from obstetric causes was treated by dialysis at a single centre from 1956 to 1987. One-year survival was 78.6%, which compares favourably with other causes of ARF. Abortion, haemorrhage and preclampsia comprised 95% of cases, with survival being best (82.9%) with abortion. Survival was adversely affected by increasing age. Acute cortical necrosis (12.7% of patients) carried 100% mortality after 6 years. Follow-up of survivors showed normal renal function up to 31 years following ARF; 25-year patient survival was 71.6%. Improvements in obstetric care and the disappearance of illegal abortions have resulted in a dramatic decline in the incidence of obstetric ARF.

Induced abortion and adolescent mental health.

PubMed

Stotland, Nada L

2011-10-01

Induced abortion is widely believed - by the public, healthcare professionals, and policy-makers - to lead to adverse mental health sequelae. This belief is false, as it applies both to adult women and adolescents. However, it has been used to rationalize, and been quoted in, restrictive and intrusive legislation in several states and in proposed federal legislation. It is essential for gynecologists to have accurate information, as clinicians, for their patients, and, as key experts, for policy makers. New articles concluding that there are adverse psychological outcomes from induced abortion continue to be published. The methodological flaws in these articles are so serious as to invalidate those conclusions. Several recent scholarly analyses detail these flaws. Methodologically sound studies and reviews continue to demonstrate that psychosocial problems play a role in unwanted conception and the decision to abort unwanted pregnancies but are not the result of abortion. Clinicians may have to reassure patients making decisions about their pregnancies that abortion does not cause psychiatric illness. They can do so on the basis of recent analyses substantiating that finding. (C) 2011 Lippincott Williams & Wilkins, Inc.

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.

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

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.

Perforation and mortality after cleansing enema for acute constipation are not rare but are preventable.

PubMed

Niv, Galia; Grinberg, Tamar; Dickman, Ram; Wasserberg, Nir; Niv, Yaron

2013-01-01

Constipation is a common complaint, frequently treated with cleansing enema. Enemas can be very effective but may cause serious adverse events, such as perforation or metabolic derangement. Our aim was to evaluate the outcome of the use of cleansing enema for acute constipation and to assess adverse events within 30 days of therapy. We performed a two-phase study: an initial retrospective and descriptive study in 2010, followed by a prospective study after intervention, in 2011. According to the results of the first phase we established guidelines for the treatment of constipation in the Emergency Department and then used these in the second phase. There were 269 and 286 cases of severe constipation in the first and second periods of the study, respectively. In the first study period, only Fleet® Enema was used, and in the second, this was changed to Easy Go enema (free of sodium phosphate). There was a 19.2% decrease in the total use of enema, in the second period of the study (P < 0.0001). Adverse events and especially, the perforation rate and the 30-day mortality in patients with constipation decreased significantly in the second phase: 3 (1.4%) versus 0 (P = 0.0001) and 8 (3.9%) versus 2 (0.7%) (P = 0.0001), for perforation and death in the first and second period of the study, respectively. Enema for the treatment of acute constipation is not without adverse events, especially in the elderly, and should be applied carefully. Perforation, hyperphosphatemia (after Fleet Enema), and sepsis may cause death in up to 4% of cases. Guidelines for the treatment of acute constipation and for enema administration are urgently needed.

Perforation and mortality after cleansing enema for acute constipation are not rare but are preventable

PubMed Central

Niv, Galia; Grinberg, Tamar; Dickman, Ram; Wasserberg, Nir; Niv, Yaron

2013-01-01

Objectives Constipation is a common complaint, frequently treated with cleansing enema. Enemas can be very effective but may cause serious adverse events, such as perforation or metabolic derangement. Our aim was to evaluate the outcome of the use of cleansing enema for acute constipation and to assess adverse events within 30 days of therapy. Methods We performed a two-phase study: an initial retrospective and descriptive study in 2010, followed by a prospective study after intervention, in 2011. According to the results of the first phase we established guidelines for the treatment of constipation in the Emergency Department and then used these in the second phase. Results There were 269 and 286 cases of severe constipation in the first and second periods of the study, respectively. In the first study period, only Fleet® Enema was used, and in the second, this was changed to Easy Go enema (free of sodium phosphate). There was a 19.2% decrease in the total use of enema, in the second period of the study (P < 0.0001). Adverse events and especially, the perforation rate and the 30-day mortality in patients with constipation decreased significantly in the second phase: 3 (1.4%) versus 0 (P = 0.0001) and 8 (3.9%) versus 2 (0.7%) (P = 0.0001), for perforation and death in the first and second period of the study, respectively. Conclusion Enema for the treatment of acute constipation is not without adverse events, especially in the elderly, and should be applied carefully. Perforation, hyperphosphatemia (after Fleet Enema), and sepsis may cause death in up to 4% of cases. Guidelines for the treatment of acute constipation and for enema administration are urgently needed. PMID:23658492

Practical Management of HIV-Associated Anemia in Resource-Limited Settings: Prospective Observational Evaluation of a New Mozambican Guideline

PubMed Central

Silva, Wilson P.; Vermund, Sten H.; Valverde, Emilio; Buene, Manuel; Moon, Troy D.

2016-01-01

Abstract Mozambique's updated guideline for management of HIV-associated anemia prompts clinicians to consider opportunistic conditions, adverse drug reactions, and untreated immunosuppression in addition to iron deficiency, intestinal helminthes, and malaria. We prospectively evaluated this guideline in rural Zambézia Province. Likely cause(s) of anemia were determined through prespecified history, physical examination, and laboratory testing. Diagnoses were “etiologic” if laboratory confirmed (sputum microscopy, blood culture, Plasmodium falciparum malaria rapid test) or “syndromic” if not. To assess hemoglobin response, we used serial point-of-care measurements. We studied 324 ambulatory, anemic (hemoglobin <10 g/dl) HIV-infected adults. Study clinicians treated nearly all [315 (97.2%)] for suspected iron deficiency and/or helminthes; 56 (17.3%) had laboratory-confirmed malaria. Other assigned diagnoses included tuberculosis [30 (9.3%)], adverse drug reactions [26 (8.0%)], and bacteremia [13 (4.1%)]. Etiologic diagnosis was achieved in 79 (24.4%). Of 169 (52.2%) subjects who improved (hemoglobin increase of ≥1 g/dl without indications for hospitalization), only 65 (38.5%) received conventional management (iron supplementation, deworming, and/or antimalarials) alone. Thirty (9.3%) died and/or were hospitalized, and 125 (38.6%) were lost to follow-up. Multivariable linear and logistic regression models described better hemoglobin responses and/or outcomes in subjects with higher CD4+ T-lymphocyte counts, pre-enrollment antiretroviral therapy and/or co-trimoxazole prophylaxis, discontinuation of zidovudine for suspected adverse reaction, and smear-positive tuberculosis. Adverse outcomes were associated with fever, low body mass index, bacteremia, esophageal candidiasis, and low or missing CD4+ T cell counts. In this severely resource-limited setting, successful anemia management often required interventions other than conventional presumptive treatment, thus supporting Mozambique's guideline revision. PMID:26178574

[Results of provisional use of a system for voluntary anonymous reporting of incidents that threaten patient safety in the emergency medical services of Asturias].

PubMed

Galván Núñez, Pablo; Santander Barrios, María Dolores; Villa Álvarez, María Cristina; Castro Delgado, Rafael; Alonso Lorenzo, Julio C; Arcos González, Pedro

2016-06-01

To describe the reported incidents and adverse events in the emergency medical services of Asturias, Spain, and assess their consequences, delays caused, and preventability. Prospective, observational study of incidents reported by the staff of the emergency medical services of Asturias after implementation of a system devised by the researchers. Incident reports were received for 0.48% (95% CI, 0.41%-0.54%) of the emergencies attended. Patient safety was compromised in 74.7% of the reported incidents. Problems arising in the emergency response coordination center (ERCC) accounted for 37.6% of the incidents, transport problems for 13.4%, vehicular problems for 10.8%, and communication problems for 8.8%. Seventy percent of the reported incidents caused delays in care; 55% of the reported incidents that put patients at risk (according to severity assessment code ratings) corresponded to problems related to human or material resources. A total of 88.1% of the incidents reported were considered avoidable. Some type of intervention was required to attenuate the effects of 46.2% of the adverse events reported. The measures that staff members most often proposed to prevent adverse events were to increase human and material resources (28.3%), establish protocols (14.5%), and comply with quality of care recommendations (9.7%). It is important to promote a culture of safety and incident reporting among health care staff in Asturias given the number of serious adverse events. Reporting is necessary for understanding the errors made and taking steps to prevent them. The ERCC is the point in the system where incidents are particularly likely to appear and be noticed and reported.

Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

PubMed

Lehloenya, R J; Todd, G; Wallace, J; Ngwanya, M R; Muloiwa, R; Dheda, K

2016-07-01

The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied. To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection. Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated. Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions. In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings. © 2016 British Association of Dermatologists.

Analysis of medication-related malpractice claims: causes, preventability, and costs.

PubMed

Rothschild, Jeffrey M; Federico, Frank A; Gandhi, Tejal K; Kaushal, Rainu; Williams, Deborah H; Bates, David W

2002-11-25

Adverse drug events (ADEs) may lead to serious injury and may result in malpractice claims. While ADEs resulting in claims are not representative of all ADEs, such data provide a useful resource for studying ADEs. Therefore, we conducted a review of medication-related malpractice claims to study their frequency, nature, and costs and to assess the human factor failures associated with preventable ADEs. We also assessed the potential benefits of proved effective ADE prevention strategies on ADE claims prevention. We conducted a retrospective analysis of a New England malpractice insurance company claims records from January 1, 1990, to December 31, 1999. Cases were electronically screened for possible ADEs and followed up by independent review of abstracts by 2 physician reviewers (T.K.G. and R.K.). Additional in-depth claims file reviews identified potential human factor failures associated with ADEs. Adverse drug events represented 6.3% (129/2040) of claims. Adverse drug events were judged preventable in 73% (n = 94) of the cases and were nearly evenly divided between outpatient and inpatient settings. The most frequently involved medication classes were antibiotics, antidepressants or antipsychotics, cardiovascular drugs, and anticoagulants. Among these ADEs, 46% were life threatening or fatal. System deficiencies and performance errors were the most frequent cause of preventable ADEs. The mean costs of defending malpractice claims due to ADEs were comparable for nonpreventable inpatient and outpatient ADEs and preventable outpatient ADEs (mean, $64,700-74,200), but costs were considerably greater for preventable inpatient ADEs (mean, $376,500). Adverse drug events associated with malpractice claims were often severe, costly, and preventable, and about half occurred in outpatients. Many interventions could potentially have prevented ADEs, with error proofing and process standardization covering the greatest proportion of events.

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.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

PubMed

Conti, Francesca; Lugo-Reyes, Saul Oswaldo; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Güzide; Borges de Oliveira, Edgar; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G; Emiroglu, Melike; Öz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Pérez, Nestor; Regairaz, Lorena; Guidos Morales, Héctor Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Ortega, Maria Claudia; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret Bano; Vogt, Guillaume; Blanche, Stéphane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J; Kütükçüler, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, Jacinta

2016-07-01

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Our objective was to assess the effect of mycobacterial disease in patients with CGD. We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study.

PubMed

Toyos, Rolando; McGill, William; Briscoe, Dustin

2015-01-01

The purpose of this study was to determine the clinical benefits of intense-pulsed-light therapy for the treatment of dry-eye disease caused by meibomian gland dysfunction (MGD). MGD is the leading cause of evaporative dry eye disease. It is currently treated with a range of methods that have been shown to be only somewhat effective, leading to the need for advanced treatment options. A retrospective noncomparative interventional case series was conducted with 91 patients presenting with severe dry eye syndrome. Treatment included intense-pulsed-light therapy and gland expression at a single outpatient clinic over a 30-month study. Pre/post tear breakup time data were available for a subset of 78 patients. For all patients, a specially developed technique for the treatment of dry eye syndrome was applied as a series of monthly treatments until there was adequate improvement in dry eye syndrome symptoms by physician judgment, or until patient discontinuation. Primary outcomes included change in tear breakup time, self-reported patient satisfaction, and adverse events. Physician-judged improvement in dry eye tear breakup time was found for 68 of 78 patients (87%) with seven treatment visits and four maintenance visits on average (medians), and 93% of patients reported post-treatment satisfaction with degree of dry eye syndrome symptoms. Adverse events, most typically redness or swelling, were found for 13% of patients. No serious adverse events were found. Although preliminary, study results of intense-pulsed-light therapy treatment for dry eye syndrome caused by meibomian gland dysfunction are promising. A multisite clinical trial with a larger sample, treatment comparison groups, and randomized controlled trials is currently underway.

Long-term fate of depleted uranium at Aberdeen and Yuma Proving Grounds: Human health and ecological risk assessments

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

Ebinger, M.H.; Beckman, R.J.; Myers, O.B.

1996-09-01

The purpose of this study was to evaluate the immediate and long-term consequences of depleted uranium (DU) in the environment at Aberdeen Proving Ground (APG) and Yuma Proving Ground (YPG) for the Test and Evaluation Command (TECOM) of the US Army. Specifically, we examined the potential for adverse radiological and toxicological effects to humans and ecosystems caused by exposure to DU at both installations. We developed contaminant transport models of aquatic and terrestrial ecosystems at APG and terrestrial ecosystems at YPG to assess potential adverse effects from DU exposure. Sensitivity and uncertainty analyses of the initial models showed the portionsmore » of the models that most influenced predicted DU concentrations, and the results of the sensitivity analyses were fundamental tools in designing field sampling campaigns at both installations. Results of uranium (U) isotope analyses of field samples provided data to evaluate the source of U in the environment and the toxicological and radiological doses to different ecosystem components and to humans. Probabilistic doses were estimated from the field data, and DU was identified in several components of the food chain at APG and YPG. Dose estimates from APG data indicated that U or DU uptake was insufficient to cause adverse toxicological or radiological effects. Dose estimates from YPG data indicated that U or DU uptake is insufficient to cause radiological effects in ecosystem components or in humans, but toxicological effects in small mammals (e.g., kangaroo rats and pocket mice) may occur from U or DU ingestion. The results of this study were used to modify environmental radiation monitoring plans at APG and YPG to ensure collection of adequate data for ongoing ecological and human health risk assessments.« less

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

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.

40 CFR 152.46 - Notification and non-notification changes to registrations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... cause unreasonable adverse effects to the environment may be accomplished by notification to the Agency... having no potential to cause unreasonable adverse effects to the environment may be accomplished without... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Notification and non-notification...

On the Likelihood of Single-Walled Carbon Nanotubes Causing Adverse Marine Ecological Effects

EPA Science Inventory

This brief article discusses the ecological effects of single-walled carbon nanotubes (SWNTs)in the marine environment. Based on new research and a review of the scientific literature, the paper concludes that SWNTs are unlikely to cause adverse ecological effects in the marine ...

[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 .

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

PubMed

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

2017-08-01

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

Monitoring drug safety in Astrakhan, Russia.

PubMed

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

2015-01-01

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

Pathophysiology of pulmonary hypertension in acute lung injury

PubMed Central

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

Lessons learnt from Dental Patient Safety Case Reports

PubMed Central

Obadan, Enihomo M.; Ramoni, Rachel B.; Kalenderian, Elsbeth

2015-01-01

Background Errors are commonplace in dentistry, it is therefore our imperative as dental professionals to intercept them before they lead to an adverse event, and/or mitigate their effects when an adverse event occurs. This requires a systematic approach at both the profession-level, encapsulated in the Agency for Healthcare Research and Quality’s Patient Safety Initiative structure, as well as at the practice-level, where Crew Resource Management is a tested paradigm. Supporting patient safety at both the dental practice and profession levels relies on understanding the types and causes of errors, an area in which little is known. Methods A retrospective review of dental adverse events reported in the literature was performed. Electronic bibliographic databases were searched and data were extracted on background characteristics, incident description, case characteristics, clinic setting where adverse event originated, phase of patient care that adverse event was detected, proximal cause, type of patient harm, degree of harm and recovery actions. Results 182 publications (containing 270 cases) were identified through our search. Delayed and unnecessary treatment/disease progression after misdiagnosis was the largest type of harm reported. 24.4% of reviewed cases were reported to have experienced permanent harm. One of every ten case reports reviewed (11.1%) reported that the adverse event resulted in the death of the affected patient. Conclusions Published case reports provide a window into understanding the nature and extent of dental adverse events, but for as much as the findings revealed about adverse events, they also identified the need for more broad-based contributions to our collective body of knowledge about adverse events in the dental office and their causes. Practical Implications Siloed and incomplete contributions to our understanding of adverse events in the dental office are threats to dental patients’ safety. PMID:25925524

Importance of ticks and their chemical and immunological control in livestock*

PubMed Central

Rajput, Zahid Iqbal; Hu, Song-hua; Chen, Wan-jun; Arijo, Abdullah G.; Xiao, Chen-wen

2006-01-01

The medical and economic importance of ticks has long been recognized due to their ability to transmit diseases to humans and animals. Ticks cause great economic losses to livestock, and adversely affect livestock hosts in several ways. Loss of blood is a direct effect of ticks acting as potential vector for haemo-protozoa and helminth parasites. Blood sucking by large numbers of ticks causes reduction in live weight and anemia among domestic animals, while their bites also reduce the quality of hides. However, major losses caused by ticks are due to their ability to transmit protozoan, rickettsial and viral diseases of livestock, which are of great economic importance world-wide. There are quite a few methods for controlling ticks, but every method has certain shortcomings. The present review is focused on ticks importance and their control. PMID:17048307

[A Case of Recurrent Stenosis after Metallic Stenting for Esophagogastric Junction Adenocarcinoma with Peritoneal Metastases].

PubMed

Hirakawa, Toshiki; Morimoto, Junya; Nakazawa, Kazunori; Miyamoto, Hironari; Okada, Takuma; Nobori, Chihoko; Kurihara, Shigeaki; Wang, En; Aomatsu, Naoki; Iwauchi, Takehiko; Yamagata, Shigehito; Uchima, Yasutake; Takeuchi, Kazuhiro

2017-11-01

A 65-year-old man presented with severe strictures from the esophagogastric junction to the body of the stomach and was histopathologically diagnosed with adenocarcinoma. Computed tomography showed multiple peritoneal metastases. A long, covered metallic stent was placed, and chemotherapy was started. Subsequent granulation from the oral side of the stent caused stricture formation, and a covered stent was also placed. After 8 months, granulation from the oral side of the stent caused recurrent stricture formation. We again placed a metallic stent. Successful chemotherapy for stomach cancer with long-term benefit is possible with new molecularly targeted drugs. Stenting may cause adverse events such as stenosis, but can enable oral intake and is minimally invasive. This report describes a case that required multiple stent placement and reviews the relevant literature.

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

PubMed

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

2015-11-06

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

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

PubMed Central

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

2015-01-01

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

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

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.

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.

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

PubMed Central

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

PubMed

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach.

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

PubMed

Mo, Zhaojun; Mo, Yi; Li, Mingqiang; Tao, Junhui; Yang, Xu; Kong, Jilian; Wei, Dingkai; Fu, Botao; Liao, Xueyan; Chu, Jianli; Qiu, Yuanzheng; Hille, Darcy A; Nelson, Micki; Kaplan, Susan S

2017-10-13

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs. Copyright © 2017. Published by Elsevier Ltd.

The burden of age-related macular degeneration: a value-based medicine analysis.

PubMed

Brown, Gary C; Brown, Melissa M; Sharma, Sanjay; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2005-01-01

To assess the quality-of-life loss and the macroeconomic financial consequences associated with age-related macular degeneration (ARMD). Time tradeoff utility analysis was performed to assess the quality-of-life diminution caused by ARMD (both dry and neovascular) in cohorts consisting of (1) patients with ARMD, (2) ophthalmologists asked to assume they had various degrees of severity of ARMD, (3) healthcare providers asked to assume they had various degrees of severity of ARMD, and (4) participants from the general community asked to assume they had various degrees of severity of ARMD. ARMD was classified according to vision in the better-seeing eye as (1) mild: 20/20 to 20/40, (2) moderate: 20/50 to 20/100, (3) severe: < or = 20/200, or (4) very severe: < or = 20/800. Mild ARMD caused a 17% decrement in the quality of life of the average patient, similar to that encountered with moderate cardiac angina or symptomatic human immunodeficiency virus syndrome. Moderate ARMD caused a 32% decrease in the average patient's quality of life, similar to that associated with severe cardiac angina or a fractured hip. Severe ARMD caused a 53% decrease in quality, more than that of dialysis, and very severe ARMD caused a 60% decrease in the average ARMD patient's quality of life, similar to that encountered with end-stage prostate cancer or a catastrophic stroke that leaves a person bedridden, incontinent, and requiring constant nursing care. Patients with varying degrees of severity of ARMD were found to have quality-of-life impairment ranging from 96% to 750% greater than that estimated by treating ophthalmologists for the same condition. An economic analysis based upon losses to the gross domestic product suggests that ARMD has approximately a $30 billion annual negative impact. The return on investment is therefore potentially high for both treatment with current ARMD therapies and the research costs invested in the development of new ARMD treatment modalities. ARMD is a major public health problem that has a devastating effect upon patients and marked adverse financial consequences for the economy.

THE BURDEN OF AGE-RELATED MACULAR DEGENERATION: A VALUE-BASED MEDICINE ANALYSIS

PubMed Central

Brown, Gary C; Brown, Melissa M; Sharma, Sanjay; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2005-01-01

Purpose To assess the quality-of-life loss and the macroeconomic financial consequences associated with age-related macular degeneration (ARMD). Methods Time tradeoff utility analysis was performed to assess the quality-of-life diminution caused by ARMD (both dry and neovascular) in cohorts consisting of (1) patients with ARMD, (2) ophthalmologists asked to assume they had various degrees of severity of ARMD, (3) healthcare providers asked to assume they had various degrees of severity of ARMD, and (4) participants from the general community asked to assume they had various degrees of severity of ARMD. ARMD was classified according to vision in the better-seeing eye as (1) mild: 20/20 to 20/40, (2) moderate: 20/50 to 20/100, (3) severe: ≤ 20/200, or (4) very severe: ≤ 20/800. Results Mild ARMD caused a 17% decrement in the quality of life of the average patient, similar to that encountered with moderate cardiac angina or symptomatic human immunodeficiency virus syndrome. Moderate ARMD caused a 32% decrease in the average patient’s quality of life, similar to that associated with severe cardiac angina or a fractured hip. Severe ARMD caused a 53% decrease in quality, more than that of dialysis, and very severe ARMD caused a 60% decrease in the average ARMD patient’s quality of life, similar to that encountered with end-stage prostate cancer or a catastrophic stroke that leaves a person bedridden, incontinent, and requiring constant nursing care. Patients with varying degrees of severity of ARMD were found to have quality-of-life impairment ranging from 96% to 750% greater than that estimated by treating ophthalmologists for the same condition. An economic analysis based upon losses to the gross domestic product suggests that ARMD has approximately a $30 billion annual negative impact. The return on investment is therefore potentially high for both treatment with current ARMD therapies and the research costs invested in the development of new ARMD treatment modalities. Conclusions ARMD is a major public health problem that has a devastating effect upon patients and marked adverse financial consequences for the economy. PMID:17057801

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.

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

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).

Real-World Multicenter Registry of Patients with Severe Coronary Artery Calcification Undergoing Orbital Atherectomy.

PubMed

Lee, Michael S; Shlofmitz, Evan; Kaplan, Barry; Alexandru, Dragos; Meraj, Perwaiz; Shlofmitz, Richard

2016-08-01

We evaluated the safety and efficacy of orbital atherectomy in real-world patients with severe coronary artery calcification (CAC). The presence of severe CAC increases the complexity of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. Atherectomy may be an indispensable tool for uncrossable or undilatable lesions by modifying severe CAC. Although the ORBIT I and II trials report that orbital atherectomy was safe and effective for the treatment of severe CAC, patients with kidney disease, recent myocardial infarction, long diffuse disease, severe left ventricular dysfunction, and unprotected left main disease were excluded. This retrospective study included 458 consecutive patients with severe CAC who underwent orbital atherectomy followed by stenting from October 2013 to December 2015 at 3 centers. The primary endpoint of major adverse cardiac and cerebrovascular events at 30 days was 1.7%. Low rates of 30-day all-cause mortality (1.3%), myocardial infarction (1.1%), target vessel revascularization (0%), stroke (0.2%), and stent thrombosis (0.9%) were observed. Angiographic complications were low: perforation was 0.7%, dissection 0.9%, and no-reflow 0.7%. Emergency coronary artery bypass graft surgery was performed in 0.2% of patients. In the largest real-world study of patients who underwent orbital atherectomy, including high-risk patients who were not surgical candidates as well as those with very complex coronary anatomy, acute and short-term adverse clinical event rates were low. A randomized clinical trial is needed to identify the ideal treatment strategy for patients with severe CAC. © 2016 The Authors. Journal of Interventional Cardiology Published by Wiley Periodicals, Inc.

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.

Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

PubMed

Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

2012-09-01

The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

[Causes of underreporting of occupational injuries and adverse events in Chile].

PubMed

Luengo, Carolina; Paravic, Tatiana; Valenzuela, Sandra

2016-02-01

Objective To describe the causes of underreporting of occupational injuries and adverse events as identified in the international literature and by key informants in the area of health and risk prevention in Chile. Methods The study uses a qualitative descriptive approach. This includes a systematized literature review that follows the SALSA method (Search, Appraisal, Synthesis and Analysis) and is in line with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In addition, interviews were conducted with informants in the area of health and risk prevention in Chile. Results The leading causes of underreporting of occupational injuries as described in the literature and by key informants were economic factors and ignorance. With regard to adverse events, the principal causes indicated were fear of sanctions, limited support provided by the authorities, lack of knowledge, and excessive workload. Conclusions It is important to continue working to strengthen the reporting of occupational injuries and adverse events and to implement measures aimed at minimizing factors that appear to be the leading causes of underreporting. In the case of occupational injuries, this means making sure that economic factors are not an impediment but rather an incentive to reporting. With respect to adverse events, steps should be taken to eliminate the fear of sanctions and to develop recommendations, focusing more on systemic improvements than on individuals, to promote joint learning. In both cases it will be necessary to combat ignorance through continuous, systematic training and support.

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.

Cisplatin-induced hypokalemic paralysis.

PubMed

Mohammadianpanah, Mohammad; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-08-01

Profound hypokalemic conditions resulting from cisplatin therapy have been known to produce hypokalemic paralysis in rare cases. We describe such a case of cisplatin-induced hypokalemic paralysis. A 15-year-old Persian girl with ovarian dysgerminoma presented with severe generalized weakness and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On physical examination, there was symmetric flaccid paralysis and areflexia in all of the extremities and particularly in the lower limbs. Her serum potassium concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive systemic evaluation. Complete clinical and paraclinical recovery was achieved after short-term administration of potassium supplement. Adverse drug reactions are common with cisplatin, but the drug is only rarely associated with hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in this case. This adverse drug event--whether isolated or secondary to hypomagnesemia--may be deceptive, leading to a fatal mistake in the oncology setting, and should therefore be precisely differentiated from cancer-related complications. This case suggests that cisplatin should be added to the list of agents causing hypokalemic paralysis. Regular serum electrolyte measurement, the early detection of cation deficiency, and appropriate replacement of cations are all recommended.

A review of the evidence for endocrine disrupting effects of current-use chemicals on wildlife populations.

PubMed

Matthiessen, Peter; Wheeler, James R; Weltje, Lennart

2018-03-01

This review critically examines the data on claimed endocrine-mediated adverse effects of chemicals on wildlife populations. It focuses on the effects of current-use chemicals, and compares their apparent scale and severity with those of legacy chemicals which have been withdrawn from sale or use, although they may still be present in the environment. The review concludes that the effects on wildlife of many legacy chemicals with endocrine activity are generally greater than those caused by current-use chemicals, with the exception of ethinylestradiol and other estrogens found in sewage effluents, which are causing widespread effects on fish populations. It is considered that current chemical testing regimes and risk assessment procedures, at least those to which pesticides and biocides are subjected, are in part responsible for this improvement. This is noteworthy as most ecotoxicological testing for regulatory purposes is currently focused on characterizing apical adverse effect endpoints rather than identifying the mechanism(s) responsible for any observed effects. Furthermore, a suite of internationally standardized ecotoxicity tests sensitive for potential endocrine-mediated effects is now in place, or under development, which should ensure further characterization of substances with these properties so that they can be adequately regulated.

Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity ?

PubMed Central

Herskind, Carsten; Talbot, Christopher J.; Kerns, Sarah L.; Veldwijk, Marlon R.; Rosenstein, Barry S.; West, Catharine M. L.

2016-01-01

Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy. PMID:26944314

Mobile Microbiome

PubMed Central

Han, Y.W.; Wang, X.

2013-01-01

The link between oral infections and adverse systemic conditions has attracted much attention in the research community. Several mechanisms have been proposed, including spread of the oral infection due to transient bacteremia resulting in bacterial colonization in extra-oral sites, systemic injury by free toxins of oral pathogens, and systemic inflammation caused by soluble antigens of oral pathogens. Mounting evidence supports a major role of the systemic spread of oral commensals and pathogens to distant body sites causing extra-oral infections and inflammation. We review here the most recent findings on systemic infections and inflammation complicated by oral bacteria, including cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, respiratory tract infections, and organ inflammations and abscesses. The recently identified virulence mechanisms of oral species Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Campylobacter rectus are also reviewed. A pattern emerges indicating that only select subtype(s) of a given species, e.g., F. nucleatum subspecies animalis and polymorphum and S. mutans non-c serotypes, are prone to extra-oral translocation. These findings advocate the importance of identification and quantification of potential pathogens at the subtype levels for accurate prediction of disease potential. PMID:23625375

40 CFR 717.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR... adverse reaction to health or the environment. (b) Firm or company means any person, that is subject to.... (i) Significant adverse reactions are reactions that may indicate a substantial impairment of normal...

40 CFR 717.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR... adverse reaction to health or the environment. (b) Firm or company means any person, that is subject to.... (i) Significant adverse reactions are reactions that may indicate a substantial impairment of normal...

Information for physicians and pharmacists about drugs that might cause dry mouth: a study of monographs and published literature.

PubMed

Nguyen, Caroline T; MacEntee, Michael I; Mintzes, Barbara; Perry, Thomas L

2014-01-01

Over three-quarters of the older population take medications that can potentially cause dry mouth. Physicians or pharmacists rarely inform patients about this adverse effect and its potentially severe damage to the teeth, mouth and general health. The objectives of this study were to (1) identify warnings in the literature about dry mouth associated with the most frequently prescribed pharmaceutical products in Canada; and (2) consider how this information might be obtained by physicians, pharmacists and patients. Monographs on the 72 most frequently prescribed medications during 2010 were retrieved from the Compendium of Pharmaceuticals and Specialties (CPS, a standard drug information reference for physicians and pharmacists), the National Library of Medicine's 'DailyMed' database, directly from the manufacturers, and from a systematic search of biomedical journals. The CPS provided monographs for 43% of the medications, and requests to manufacturers produced the remaining monographs. Mentions of dry mouth were identified in 61% of the products (43% amongst CPS monographs; an additional 43% amongst manufacturers' monographs; 7% in the DailyMed database and 7% from biomedical journals); five medications had contradictory reports in different monographs. Nearly two-thirds (61%) of the most commonly prescribed medications can cause dry mouth, yet warnings about this adverse effect and its potentially serious consequences are not readily available to physicians, pharmacists, dentists or patients.

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.

The role of mental health, personality disorders and childhood adversities in relation to life satisfaction in a sample of general population.

PubMed

Rissanen, Teemu; Viinamäki, Heimo; Lehto, Soili M; Hintikka, Jukka; Honkalampi, Kirsi; Saharinen, Tarja; Koivumaa-Honkanen, Heli

2013-04-01

Mental health disorders are one of the leading causes of the disease burden globally. The aim of this population-based study was to investigate the relationship between life satisfaction and mental health by taking into account its less studied areas, such as personality disorders and childhood adversities. The sample of this cross-sectional study was derived from a population-based Kuopio Depression Study performed in Eastern Finland. Health questionnaires were mailed in 1998, 1999, 2001 and 2005 including questions on several clinical factors. Questions on childhood home were asked in 1999. The inclusion criteria for the final study sample in 2005 were based on previously repeatedly (1998, 1999, 2001) reported life satisfaction, depression or alexithymic features (with/without). Psychiatric diagnoses of major depressive disorder and personality disorder were confirmed by structured clinical interview I and II for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationships. In general, the broad spectrum of poor mental health indicators was associated with concurrent life dissatisfaction. After multiple adjustments, major depressive disorder (MDD), hopelessness and mental distress remained independent correlates of life dissatisfaction, while personality disorder or self-reported childhood adversities lost their significance when these other factors were included in the model. Mental health is closely interwoven with life satisfaction. Even if personality disorder and childhood adversities were significant correlates of life dissatisfaction, adverse concurrent mental symptoms and features and MDD were its strongest correlates.

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

PubMed

Rossi, C; Reginelli, A; D'Amora, M; Di Grezia, G; Mandato, Y; D'Andrea, A; Brunese, L; Grassi, R; Rotondi, A

2014-01-01

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

Omeprazole- and Esomeprazole-associated Hypomagnesaemia: Data Mining of the Public Version of the FDA Adverse Event Reporting System

PubMed Central

Tamura, Takao; Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2012-01-01

Objective: Case reports showing that proton-pump inhibitors (PPIs), omeprazole and esomeprazole, can cause hypomagnesaemia have been accumulating since 2006. In this study, the reports submitted to the Adverse Event Reporting System (AERS) of the US Food and Drug Administration (FDA) were evaluated to assess omeprazole and esomeprazole in terms of susceptibility to hypomagnesaemia. Methods: After a revision of arbitrary drug names and the deletion of duplicated submissions, the reports involving omeprazole and esomeprazole were analyzed. Standardized official pharmacovigilance tools were used for the quantitative detection of a signal, i.e., an association between a drug and an adverse drug event, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results: A total of 22,017,956 co-occurrences were found in 1,644,220 reports from 2004 to 2009, where a co-occurrence was a pair of a drug and an adverse drug event. In total, 818 and 743 adverse drug events were listed as omeprazole- and esomeprazole-associated, with hypomagnesaemia ranking 85th and 135th, respectively. Although both PPIs were associated with hypomagnesaemia, the statistical metrics suggested that the association was more noteworthy for omeprazole. Conclusion: The data obtained in this study do not provide sufficient evidence to recommend systematic monitoring of magnesium levels in plasma, but chronic exposure to a PPI can lead to severe hypomagnesaemia. PMID:22745572

Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

PubMed

Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

2015-01-01

Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

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

PubMed

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

2009-01-01

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

Severe unexpected adverse effects after permanent eye makeup and their management by Q-switched Nd:YAG laser

PubMed Central

Goldman, Alberto; Wollina, Uwe

2014-01-01

Permanent makeup is a cosmetic tattoo that is used to enhance one’s appearance, and which has become more popular among middle-aged and elderly women. A couple of benefits seem to be associated with permanent tattoos in the elderly: saving time (wake up with makeup); poor eyesight (difficult to apply makeup); and saving money. On the other hand, cosmetic tattoos bear the same risks as other tattoo procedures. We report on fading and unintended hyperpigmentation after tattooing on eyebrows and eyelids, and discuss the scientific and anatomical background behind the possible cause. Dermatochalasis may be a possible risk factor for excessive unwanted discolorations. Q-switched neodymium-doped yttrium aluminum garnet laser is an appropriate and safe therapeutic tool that can manage such adverse effects. Consumer protection warrants better information and education of the risks of cosmetic tattoos – in particular, for elderly women. PMID:25143716

Severe unexpected adverse effects after permanent eye makeup and their management by Q-switched Nd:YAG laser.

PubMed

Goldman, Alberto; Wollina, Uwe

2014-01-01

Permanent makeup is a cosmetic tattoo that is used to enhance one's appearance, and which has become more popular among middle-aged and elderly women. A couple of benefits seem to be associated with permanent tattoos in the elderly: saving time (wake up with makeup); poor eyesight (difficult to apply makeup); and saving money. On the other hand, cosmetic tattoos bear the same risks as other tattoo procedures. We report on fading and unintended hyperpigmentation after tattooing on eyebrows and eyelids, and discuss the scientific and anatomical background behind the possible cause. Dermatochalasis may be a possible risk factor for excessive unwanted discolorations. Q-switched neodymium-doped yttrium aluminum garnet laser is an appropriate and safe therapeutic tool that can manage such adverse effects. Consumer protection warrants better information and education of the risks of cosmetic tattoos - in particular, for elderly women.

Adverse Drug Events in Children: How Big is the Problem?

PubMed

Zed, Peter J

2015-01-01

Adverse drug events in children is an under appreciated but significant cause of health care contact resulting in ED visits and hospital admissions with associated resource utilization. In recent years we have started to better understand the impact of ADEs in children but there remains significant questions that must be addressed to further improve our understanding of the etiology of these ADEs and strategies for prevention and management. This paper will describe what is known regarding the frequency, severity, preventability and classification of ADEs in children. It will also describe some of the challenges and unanswered questions regarding patient, drug and system factors, which contribute to ADEs in children. Finally, areas of future research will be identified to further improve our understanding of ADEs in children to inform prevention strategies as well as early recognition and management approaches to minimize the significant ADEs can have on children, families and our health care system.

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.

High times, low sats: diffuse pulmonary infiltrates associated with chronic synthetic cannabinoid use.

PubMed

Alhadi, Sameir; Tiwari, Anupama; Vohra, Rais; Gerona, Roy; Acharya, Janak; Bilello, Kathryn

2013-06-01

In recent years, cases of severe adverse effects from recreational use of synthetic cannabinoids (SC) have established that these agents represent a novel toxicologic hazard. A 21-year-old male presenting as a vehicular trauma victim was noted with diffuse pulmonary infiltrates related to chronic inhalation of multiple synthetic cannabinoid-containing products. Chest imaging revealed bilateral, subacute lung infiltrates; histopathological analysis of bronchial and alveolar tissues revealed an inflammatory process. An extensive workup failed to identify infectious, malignant, autoimmune, or hematologic causes of the syndrome, and toxicological analysis of the blood and body fluids confirmed the presence of multiple synthetic cannabinoids and metabolites. The patient recovered after an 8-day ICU course, wherein he received antibiotics, steroids, and mechanical ventilation. This case contributes to the currently evolving knowledge about SC agents, adding a rarely described pulmonary complication to the growing list of adverse effects associated with these products.

Surgical Adverse Events, Risk Management, and Malpractice Outcome: Morbidity and Mortality Review Is Not Enough

PubMed Central

Morris, John A.; Carrillo, Ysela; Jenkins, Judith M.; Smith, Philip W.; Bledsoe, Sandy; Pichert, James; White, Andrew

2003-01-01

Objective To review all admissions (age > 13) to three surgical patient care centers at a single academic medical center between January 1, 1995, and December 6, 1999, for significant surgical adverse events. Summary Background Data Little data exist on the interrelationships between surgical adverse events, risk management, malpractice claims, and resulting indemnity payments to plaintiffs. The authors hypothesized that examination of this process would identify performance improvement opportunities overlooked by standard medical peer review; the risk of litigation would be constant across the three homogeneous patient care centers; and the risk management process would exceed the performance improvement process. Methods Data collected included patient demographics (age, gender, and employment status), hospital financials (hospital charges, costs, and financial class), and outcome. Outcome categories were medical (disability: <1 month, 1–6 months, permanent/death), legal (no legal action, settlement, summary judgment), financial (indemnity payments, legal fees, write-offs), and cause and effect analysis. Cause and effect analysis attempts to identify system failures contributing to adverse outcomes. This was determined by two independent analysts using the 17 Harvard criteria and subdividing these into subsystem causative factors. Results The study group consisted of 130 patients with surgical adverse events resulting in total liabilities of $8.2 million. The incidence of adverse events per 1,000 admissions across the three patient care centers was similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30, women’s health = $90, trauma = $520). Patient demographics were not predictive of high-risk subgroups for adverse events or litigation. In terms of medical outcome, 51 patients had permanent disability or death, accounting for 98% of the indemnity payments. In terms of legal outcome, 103 patients received no indemnity payments, 15 patients received indemnity payments, four suits remain open, and in eight cases charges were written off ($0.121 million). To date, no cases have been adjudicated in court. Cause and effect analysis identified 390 system failures contributing to the adverse events (mean 3.0 failures per adverse event); there were 4.7 failures per adverse event in the 15 indemnity cases. Five categories of causes accounted for 75% of the failures (patient management, n = 104; communication, n = 89; administration, n = 33; documentation, n = 32; behavior, n = 23). The current medical review process would have identified 104 of 390 systems failures (37%). Conclusions This study demonstrates no rational link between the tort system and the reduction of adverse events. Sixty-three percent of contributing causes to adverse events were undetected by current medical review processes. Adverse events occur at the interface between different systems or disciplines and result from multiple failures. Indemnity costs per hospital day vary dramatically by patient care center (range $3.60–97.60 a day). The regionalization of healthcare is in jeopardy from the burden of high indemnity payments. PMID:12796581

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

Acute Generalized Exanthematous Pustulosis Due to Insect Bites?

PubMed

Bhat, Yasmeen J; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Wani, Rohi

2015-01-01

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs and rarely associated with viral infections, food allergens or toxins. Here we present the report of three patients who got admitted in our hospital for generalized pustulosis and fever after insect bites. The diagnosis of acute generalized exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was excluded and spider bite was implicated as the etiological agent in these cases of AGEP which are the first such reported cases in India.

Effect of a herbal compound for treatment of sarcoptic mange infestations on dogs.

PubMed

Das, S S

1996-06-01

Charmil gel, a herbal product was tried against Sarcoptes scabei var canis on dogs and its efficacy was compared with that of amitraz. Mite scrapings examined at scheduled intervals after the topical application of Charmil gel caused complete recovery after 14 days in severe infestation and 7 to 10 days in mild to moderate infestations with regrowth of hair on Day 28 post-treatment. No adverse reactions were observed except mild irritation and restlessness, which persisted for a few hours soon after application.

Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

PubMed Central

Muzny, Christina A.; Schwebke, Jane R.

2016-01-01

In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. This information is vital for the prevention and control of this important infection and its adverse public health consequences. PMID:27449868

Exposure to Cobalt Causes Transcriptomic and Proteomic Changes in Two Rat Liver Derived Cell Lines

DTIC Science & Technology

2013-12-01

although contact with cobalt can cause dermatitis [16]. While cobalt is known to cause adverse health effects, the exact mechanism of action remains...animals and humans through various exposure routes. Cobalt can enter the body through respiration, ingestion, or contact with the skin. The adverse...concentration on the liver, kidney and heart in mice. Orthop Surg 2: 134–140. 16. Schwartz L PS (1945) Allergic dermatitis due to metallic cobalt. Journal

A new cause of ischaemic priapism: Synthetic cannabinoids.

PubMed

Ortac, M; Pazır, Y; Kadıoğlu, A

2018-04-01

Priapism is a urological emergency that needs early intervention and may lead to irreversible cavernosal damage. Ischaemic priapism is the most common type, which is frequently idiopathic and commonly associated with haematological diseases, medications or recreational drugs. Synthetic cannabinoids (SCs) have been increasingly used all over the world, particularly among young-adult population. SCs can cause severe adverse effects on several organ systems. However, there are no studies in the literature which have stated the possible relationship between using of SCs and priapism. We present a case of 28-year-old man who was diagnosed with a 58-hr lasting priapism after regular administrations of SCs. The priapism did not resolve neither after applying aspiration with irrigation nor shunt surgery. Finally, penile prosthesis implantation was performed as last treatment option. The SCs have been increasingly used among young population in recent years; therefore, new SC-related ischaemic priapism cases might be encountered in the emergency departments. © 2018 Blackwell Verlag GmbH.

Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

PubMed

Lystrup, Robert M; Leggit, Jeffery C

2015-08-01

Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

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.

Subject Reaction to Human-Caused and Naturally-Occurring Radioactive Threat.

ERIC Educational Resources Information Center

Belford, Susan; Gibbs, Margaret

While research has shown that people are adversely psychologically affected by knowledge that their communities have been toxically contaminated, it has been suggested that those who see a disaster as naturally occurring tend to be less adversely affected than those who see a disaster as caused by human acts. To examine this issue, questionnaires…

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.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

PubMed

Lavonas, Eric J; Banner, William; Bradt, Pamela; Bucher-Bartelson, Becki; Brown, Kimberly R; Rajan, Pradeep; Murrelle, Lenn; Dart, Richard C; Green, Jody L

2013-11-01

To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children. Copyright © 2013 Mosby, Inc. All rights reserved.

Childhood adversities and clinical symptomatology in first-episode psychosis.

PubMed

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

2017-12-01

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

VEP Responses to Op-Art Stimuli

PubMed Central

O’Hare, Louise; Clarke, Alasdair D. F.; Pollux, Petra M. J.

2015-01-01

Several types of striped patterns have been reported to cause adverse sensations described as visual discomfort. Previous research using op-art-based stimuli has demonstrated that spurious eye movement signals can cause the experience of illusory motion, or shimmering effects, which might be perceived as uncomfortable. Whilst the shimmering effects are one cause of discomfort, another possible contributor to discomfort is excessive neural responses: As striped patterns do not have the statistical redundancy typical of natural images, they are perhaps unable to be encoded efficiently. If this is the case, then this should be seen in the amplitude of the EEG response. This study found that stimuli that were judged to be most comfortable were also those with the lowest EEG amplitude. This provides some support for the idea that excessive neural responses might also contribute to discomfort judgements in normal populations, in stimuli controlled for perceived contrast. PMID:26422207

VEP Responses to Op-Art Stimuli.

PubMed

O'Hare, Louise; Clarke, Alasdair D F; Pollux, Petra M J

2015-01-01

Several types of striped patterns have been reported to cause adverse sensations described as visual discomfort. Previous research using op-art-based stimuli has demonstrated that spurious eye movement signals can cause the experience of illusory motion, or shimmering effects, which might be perceived as uncomfortable. Whilst the shimmering effects are one cause of discomfort, another possible contributor to discomfort is excessive neural responses: As striped patterns do not have the statistical redundancy typical of natural images, they are perhaps unable to be encoded efficiently. If this is the case, then this should be seen in the amplitude of the EEG response. This study found that stimuli that were judged to be most comfortable were also those with the lowest EEG amplitude. This provides some support for the idea that excessive neural responses might also contribute to discomfort judgements in normal populations, in stimuli controlled for perceived contrast.

[Post-marketing clinical study of traditional Chinese medicine--lessons learned from comprehensive evaluation of Fufang Zaoren capsule].

PubMed

Qing, Shan; Gao, Lin; Zhang, Li; Jia, Jian-Ping; Liu, Xin-Min; Ji, Shao-Liang; Yang, Xiao-Hui

2013-11-01

By comprehensive review and analysis of post-marketing clinical research on the efficacy and safety,we concluded that Fufang Zaoren capsule has certain therapeutic effects for insomnia, although current clinical research design needs improving. The post-marketing clinical studies also showed that it causes several adverse reactions at the recommended doses, such as chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, whereas high doses of Fufang Zaoren capsule can cause delayed extrapyramidal symptoms. Health Canada government website also prompted the L-tetrahydropalmatine in Fufang Zaoren capsule caused liver damage in pregnant women. The authors summarized the risk points, factors and risk control in the clinical use of Fufang Zaoren capsule and also present their perspective on the research status, existing problems and corresponding countermeasures in the post-marketing clinical re-evaluation of traditional Chinese medicine.

Tranexamic acid-associated seizures: Causes and treatment.

PubMed

Lecker, Irene; Wang, Dian-Shi; Whissell, Paul D; Avramescu, Sinziana; Mazer, C David; Orser, Beverley A

2016-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients. © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Tranexamic acid–associated seizures: Causes and treatment

PubMed Central

Lecker, Irene; Wang, Dian‐Shi; Whissell, Paul D.; Avramescu, Sinziana; Mazer, C. David

2015-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26 PMID:26580862

Early adversity and risk for moderate to severe unipolar depressive disorder in adolescence and adulthood: A register-based study of 978,647 individuals.

PubMed

Dahl, Signe Kirk; Larsen, Janne Tidselbak; Petersen, Liselotte; Ubbesen, Mads Bonde; Mortensen, Preben Bo; Munk-Olsen, Trine; Musliner, Katherine Louise

2017-05-01

Early adversity is a known risk factor for unipolar depression. We examined the impact of 9 types of early adversity on risk for moderate to severe unipolar depression in adolescence or adulthood, and evaluated whether these effects were moderated by gender and adversity timing. We conducted a prospective, population-based cohort study using Danish national registers. The sample included all individuals born in Denmark between 1980 and 1998 (N=978,647). Exposure to early adversity was assessed from ages 0-15. Types of adversity included parental illness, incarceration, death, disability, and psychiatric diagnosis; family disruption; out-of-home care; and childhood abuse. Individuals were followed from age 15 until first in- or outpatient depression diagnosis (ICD-10 codes F32, F33) in a psychiatric hospital, death, emigration, or December 31st, 2013, whichever came first. Hazard ratios (HRs) were calculated using Cox regressions. All adversities were significantly associated with increased risk for moderate to severe adolescent/adult depression (HR range: 1.30-2.72), although the effects were attenuated after mutual adjustment (adjusted HR range: 1.06-1.70). None of the effects were moderated by gender. The effect of family disruption was strongest between ages 0-4 (HR=1.66, 95% CI=1.61-1.71), while the effect of out-of-home care was strongest between ages 10-14 (HR=2.45, 95% CI=2.28-2.64). Untreated and primary-care treated depression were not measured. Our results support past findings that multiple types of early adversity increase risk for moderate to severe unipolar depression in adolescence and adulthood. Certain adversities may be more harmful if they occur during specific developmental time periods. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular Diagnosis of Thalassemias and Hemoglobinopathies: An ACLPS Critical Review.

PubMed

Sabath, Daniel E

2017-07-01

To describe the use of molecular diagnostic techniques for patients with hemoglobin disorders. A clinical scenario is presented in which molecular diagnosis is important for genetic counseling. Globin disorders, techniques for their diagnosis, and the role of molecular genetic testing in managing patients with these disorders are described in detail. Hemoglobin disorders, including thalassemias and hemoglobinopathies, are among the commonest genetic diseases, and the clinical laboratory is essential for the diagnosis of patients with these abnormalities. Most disorders can be diagnosed with protein-based techniques such as electrophoresis and chromatography. Since severe syndromes can result due to inheritance of combinations of globin genetic disorders, genetic counseling is important to prevent adverse outcomes. Protein-based methods cannot always detect potentially serious thalassemia disorders; in particular, α-thalassemia may be masked in the presence of β-thalassemia. Deletional forms of β-thalassemia are also sometimes difficult to diagnose definitively with standard methods. Molecular genetic testing serves an important role in identifying individuals carrying thalassemia traits that can cause adverse outcomes in offspring. Furthermore, prenatal genetic testing can identify fetuses with severe globin phenotypes. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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 event management of oral mucositis in patients with breast cancer.

PubMed

Seiler, Sabine; Kosse, Jens; Loibl, Sibylle; Jackisch, Christian

2014-04-01

Oral mucositis (OM) is a clinically important and frequent adverse event (AE) associated with cancer treatment with conventional chemotherapy as well as new targeted agents. Incidence and severity of OM vary from treatment to treatment and from patient to patient. The pathogenesis of chemotherapy-induced OM can be divided into 5 phases. OM induced by targeted therapies differs among other things in appearance, course, concomitant AEs and toxicity, and thus could be perceived as an entity distinct from chemotherapy-induced OM with an innate pathogenic mechanism. OM has a severe impact on a patient's quality of life (QoL) by causing complications such as pain and discomfort. Even more important are associated restrictions in nutrition and hydration. Thus, the efficacy of cancer therapy might be impaired due to the necessity of dose delays and dose reductions. Numerous preventive and therapeutic approaches have been evaluated, but currently no single agent has changed the standard of care in preventing and treating OM. Thus, the current management has evolved from clinical experience rather than clinical evidence. This article will review the AE 'OM' induced by breast cancer treatment with chemotherapy and targeted agents in order to provide practical guidance for management and prevention.

Haemorrhagic diarrhoea and reproductive failure in Bonsmara cattle resulting from anomalous heavy metal concentrations in soils, forages and drinking water associated with geochemical anomalies of toxic elements on the farm Puntlyf, South Africa

NASA Astrophysics Data System (ADS)

Elsenbroek, J. H.; Meyer, J.; Myburgh, J.

2003-05-01

Poor livestock health conditions are associated with geochemical Pb anomalies on a farm approximately 40km east of Pretoria, South Africa. A generic risk assessment of drinking water for Bonsmara cattle obtained from three separate subterranean water sources on the farm, revealed the presence of several potentially hazardous constituents suspected for the development of adverse health effects in the herd. The two main symptoms of the herd, namely, severe haemorrhagic diarrhoea in calves and reproductive failure in cows, have been investigated. A selenium-induced copper deficiency was proposed as the main cause to the calf diarrhoea, due to complexing between high concentrations of Se, Mo, Hg and Pb in drinking water. It was also anticipated that such Cu deficiencies would lead to low systemic Se inducing hypothyroidism in the cows due to inadequate iodine activation required for thyroid hormone formation and consequently adversely affect reproduction. The anomalous Pb in borehole drinking water on the southem part of the farm, suggests a clear genetic link with the underlying geochemical Pb anomalies detected by means of an ongoing regional geochemical survey.

Epidural conduction device fractures and complications of retained fragments.

PubMed

Fischer, Robert

2008-02-01

During the past 3 years, the US Food and Drug Administration (FDA) has received a growing number of adverse event reports on the breakage or fracturing and retention of anesthetic conduction device tips with associated complications. Serious injuries and other problems such as spinal stenosis, nerve root compression, and subcutaneous effusion can result. Several case reports demonstrate how the problems occur; some illustrate the severity of the problem. All cases are from adverse event reports in the FDA Center for Devices and Radiological Health (CDRH) Manufacturer and User Facility Device Experience database. Frequently, in the interest of not causing patient harm, a device fragment might not be removed as long as the patient is not neurologically compromised or at risk for infection or there is little potential for migration of the fragmented piece. On many occasions, the fragments remain in patients without their knowledge. The FDA wants to raise awareness of the problem and its potential impact in creating complications, encourage the practice of informing patients of the fragmented device, and promote reporting of such incidents to CDRH via the MedWatch reporting system. Based on a search of the current literature, recommendations for prevention are suggested.

Outcome of cataract surgery at one year in Kenya, the Philippines and Bangladesh.

PubMed

Lindfield, R; Kuper, H; Polack, S; Eusebio, C; Mathenge, W; Wadud, Z; Rashid, A M; Foster, A

2009-07-01

To assess the change in vision following cataract surgery in Kenya, Bangladesh and the Philippines and to identify causes and predictors of poor outcome. Cases were identified through surveys, outreach and clinics. They underwent preoperative visual acuity measurement and ophthalmic examination. Cases were re-examined 8-15 months after cataract surgery. Information on age, gender, poverty and literacy was collected at baseline. 452 eyes of 346 people underwent surgery. 124 (27%) eyes had an adverse outcome. In Kenya and the Philippines, the main cause of adverse outcome was refractive error (37% and 49% respectively of all adverse outcomes) then comorbid ocular disease (26% and 27%). In Bangladesh, this was comorbid disease (58%) then surgical complications (21%). There was no significant association between adverse outcome and gender, age, literacy, poverty or preoperative visual acuity. Adverse outcomes following cataract surgery were frequent in the three countries. Main causes were refractive error and preoperative comorbidities. Many patients are not attaining the outcomes available with modern surgery. Focus should be on correcting refractive error, through operative techniques or postoperative refraction, and on a system for assessing comorbidities and communicating risk to patients. These are only achievable with a commitment to ongoing surgical audit.

Evaluation of fish kills during November 1986 and July 1987 in upper East Fork Poplar Creek near the Y-12 Plant

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

Ryon, M.G.; Loar, J.M.; Southworth, G.R.

1990-09-01

The Environmental Sciences Division (ESD) investigated two fish kills that occurred on November 21, 1986, and July 9, 1987, in upper East Fork Poplar Creek at the outfall of New Hope Pond (NHP) below the Oak Ridge Y-12 Plant. Investigative procedures included sampling of water at the inlet and outfall of NHP for water quality, examination of operating procedures at the Y-12 Plant and in the biomonitoring program that may have adversely affected the fish populations, review of results of concurrent ambient toxicity tests of the inlet and outfall water of NHP, autopsy investigations of the cause of death ofmore » the stonerollers, and laboratory experimentation to evaluate potential causes. The investigations revealed that the cause of death was bacterial hemorrhagic septicemia caused by Aeromonas hydrophila, which is a stress-mediated disease. The specific stressor responsible for the outbreak of the disease was not identified. Several possible stresses were indicated, including elevated concentrations of mercury and chlorine, excessive electroshocking activity, and elevated levels of the pathogen. Cumulative stress due to the combination of several factors was also suggested. Elevated temperatures and overcrowding may have enhanced the spread of the epizootic but were not the primary causes. The impact on the stoneroller population below NHP was not ecologically significant. 23 refs., 3 figs., 12 tabs.« less

Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

PubMed

Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

2017-02-01

Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

76 FR 66061 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... and Reporting Requirements for Allegations of Significant Adverse Reactions to Human Health or the... Adverse Reactions to Human Health or the Environment (TSCA Section 8(c))''. ICR numbers: EPA ICR No. 1031... of significant adverse reactions to health or the environment alleged to have been caused by such...

[Adverse reaction caused by rabies vaccine in China: a Meta-analysis].

PubMed

Zhang, X R; Wu, Z G; Zhang, W S

2017-06-10

Objective: To conduct a Meta-analysis on the rate of adverse reaction related to rabies vaccine, so as to provide reference for rabies vaccine immunization in China. Methods: We electronically searched databases including CNKI, VIP information resource integration service platform, WanFang Data, CBM, PubMed and The Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using the R software. Results: A total of 29 related papers had met the inclusion criteria, with no publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94 222 respondents, with an incidence of adverse reactions as 1.04 % -47.78 % . The overall incidence rate of adverse reaction was 9.82 % (95 %CI : 7.58 % -12.72 % ). A combined local adverse reaction rate appeared as 12.05 % (95 % CI : 9.26 % -15.69 % ). The systemic adverse reaction rate was 9.06 % (95 %CI : 7.07 % -11.61 % ). The overall adverse reaction rate on aqueous vaccine was 32.39 % (95 %CI : 21.88 % -47.94 % ). Combined adverse reaction rate of freeze dried vaccine appeared as 8.65 % (95 %CI : 4.54 % -16.51 % ). Significant differences were seen between both groups ( P <0.05). Conclusions: The local adverse reaction rate caused by rabies vaccination was higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the aqueous vaccine should gradually be eliminated.

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 burden of age-related macular degeneration: a value-based analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Sharma, Sanjay; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2006-06-01

The quality-of-life loss and the financial consequences associated with age-related macular degeneration are assessed. The quality-of-life loss associated with macular degeneration is markedly underestimated by the general public, nonophthalmic physicians, and ophthalmologists who treat patients with this condition. Mild age-related macular degeneration causes a 17% decrement in the quality of life of the average patient, similar to that encountered with moderate cardiac angina or symptomatic human immunodeficiency virus syndrome. Moderate age-related macular degeneration causes a 40% decrease in the average patient's quality of life, similar to that associated with severe cardiac angina or renal dialysis. Very severe age-related macular degeneration causes a large 63% decrease in the average patient's quality of life, similar to that encountered with end-stage prostatic cancer or a catastrophic stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The return on investment is high for both treatment with current age-related macular degeneration therapies and the research costs invested in the development of age-related macular degeneration treatment modalities. Age-related macular degeneration is a major public health problem that has a devastating effect upon patients and marked adverse financial consequences for the economy.

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

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

PubMed

Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2013-12-01

Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

PubMed

Soares-Weiser, Karla; Maclehose, Harriet; Ben-Aharon, Irit; Goldberg, Elad; Pitan, Femi; Cunliffe, Nigel

2010-05-12

Rotavirus results in higher diarrhoea-related death in children less than five years of age than any other single agent, particularly in low- and middle-income countries. The World Health Organization has recommended the use of rotavirus vaccines in childhood immunization schedules. To evaluate rotavirus vaccines approved for use (Rotarix, RotaTeq, and Lanzhou Lamb Rotavirus (LLR)) for preventing rotavirus diarrhoea. In February 2010, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, and BIOSIS. We also searched the ICTRP (January 2010) and checked reference lists of identified studies. Randomized controlled trials comparing rotavirus vaccines approved for use with placebo, no intervention, or another vaccine in children. Two authors independently assessed trial eligibility, extracted data, and assessed risk of bias. Dichotomous data were combined using the risk ratio (RR) and 95% confidence intervals (CI). Thirty-four trials that included 175,944 participants met the inclusion criteria. They evaluated Rotarix (26 trials; 99,841 participants) and RotaTeq (eight trials; 76,103 participants), and had variable risk of bias (where information provided). None of the identified trials used LLR or compared rotavirus vaccines. Compared to placebo, Rotarix and RotaTeq were both effective at reducing rotavirus diarrhoea (severe cases and cases of any severity). They also reduced all-cause diarrhoea (severe cases), and hospitalizations and need for medical attention caused by rotavirus diarrhoea. However, few data were available for Rotarix and all-cause diarrhoea. Versus the placebo groups, participants in each vaccine group had similar numbers of deaths, serious adverse events, reactogenicity profiles (fever, diarrhoea, and vomiting), and adverse events that required discontinuation of the vaccination schedule. Both vaccines were immunogenic (measured by virus shedding in stool and/or seroconversion). Subgroup analyses indicate that both vaccines are effective in countries with different incomes, but few data are available. Rotarix and RotaTeq are effective vaccines for the prevention of rotavirus diarrhoea. The balance between benefit and harm favours benefit. Ongoing safety monitoring should be continued. Trials comparing LLR with placebo should be conducted and the results made available.

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.

Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection

PubMed Central

Nakamoto, Shingo; Nakamura, Masato; Jiang, Xia; Miyamura, Tatsuo; Wu, Shuang; Yokosuka, Osamu

2014-01-01

Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and Japan. Therefore, eradication of HCV may reduce the occurrence of HCC in HCV-infected individuals. In 2011, the use of first-generation HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of HCV. Administration of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected patients. However, this treatment regimen also led to severe adverse events. Second-generation direct-acting antiviral agents (DAAs) for HCV, such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates, with similar adverse events to other peg-interferon and ribavirin treatments. Higher SVR rates in HCV genotype 1- and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin, respectively. For “difficult-to-treat” HCV-infected patients, more therapeutic options are needed. Further studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments. PMID:26356295

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.

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.

Smallpox: clinical features, prevention, and management.

PubMed

Guharoy, Roy; Panzik, Robert; Noviasky, John A; Krenzelok, Edward P; Blair, Donald C

2004-03-01

To describe a general overview of smallpox, clinical presentation, diagnosis, adverse events, and management of both pre- and postexposure vaccination. Literature was identified by search of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1966-May 2003) databases using the key terms smallpox, bioterrorism, biological warfare, and smallpox vaccine. Articles identified from data sources were evaluated, and relevant information was included in this review. Smallpox is spread by human-to-human contact with an infected host and therefore can be contagious. The mortality rate for smallpox is approximately 30%. While the disease was completely eradicated by 1980 with successful use of smallpox vaccine, concern has been raised that smallpox may emerge as a tool of bioterrorism. This concern, combined with the reality of current smallpox vaccination programs in the military and selected civilian populations, mandates a clear understanding of vaccination-related adverse events and contraindications by all healthcare professionals. The vaccine may cause moderate to severe adverse events such as eczema vaccinatum, progressive vaccinia, and generalized vaccinia. The balance between the risks and benefits of mass vaccination in prevention of an epidemic is not clear. The Centers for Disease Control and Prevention has established a guideline for appropriate use of smallpox vaccine in the civilian population.

Drug Exposure and the Risk of Microscopic Colitis: A Critical Update.

PubMed

Lucendo, Alfredo J

2017-03-01

A variety of luminal antigens, including a wide range of drugs, have been associated with the still little-known pathophysiology of microscopic colitis (MC), with variable evidence suggesting causality. This article aims to review the aspects related to drugs as potential triggers of MC; to discuss the most commonly identified associations between drugs and MC; and to analyze the limitations of the studies currently available. A literature search was performed in PubMed combining the search terms 'drug exposure', 'drug consumption', and 'risk factors' with 'microscopic colitis', 'lymphocytic colitis', and 'collagenous colitis', with no language restrictions. Reference lists of retrieved documents were also reviewed. A handful of case-control studies have demonstrated significant associations between some commonly used drugs and a higher risk of developing MC. No universally accepted criteria for establishing cause-effect relationships in adverse reactions to drugs are available, but several methods that can be applied to MC, can provide degrees of the likelihood of an association. A high probability imputation in the development of MC as a drug adverse effect has only been demonstrated for individual cases by applying chronological (challenge, de-challenge, and relapse with re-challenge) and semiological criteria. Several case-control studies have shown significant associations between exposure to drugs and MC, but the variability in their design, the reference populations used, and the definitions for drug exposure considered require specific analyses. It can be concluded that drug exposure and MC as a likely cause-effect relationship has only been described for a handful of drugs and in individual cases.

Learning from malpractice claims about negligent, adverse events in primary care in the United States

PubMed Central

Phillips, R; Bartholomew, L; Dovey, S; Fryer, G; Miyoshi, T; Green, L

2004-01-01

Background: The epidemiology, risks, and outcomes of errors in primary care are poorly understood. Malpractice claims brought for negligent adverse events offer a useful insight into errors in primary care. Methods: Physician Insurers Association of America malpractice claims data (1985–2000) were analyzed for proportions of negligent claims by primary care specialty, setting, severity, health condition, and attributed cause. We also calculated risks of a claim for condition-specific negligent events relative to the prevalence of those conditions in primary care. Results: Of 49 345 primary care claims, 26 126 (53%) were peer reviewed and 5921 (23%) were assessed as negligent; 68% of claims were for negligent events in outpatient settings. No single condition accounted for more than 5% of all negligent claims, but the underlying causes were more clustered with "diagnosis error" making up one third of claims. The ratios of condition-specific negligent event claims relative to the frequency of those conditions in primary care revealed a significantly disproportionate risk for a number of conditions (for example, appendicitis was 25 times more likely to generate a claim for negligence than breast cancer). Conclusions: Claims data identify conditions and processes where primary health care in the United States is prone to go awry. The burden of severe outcomes and death from malpractice claims made against primary care physicians was greater in primary care outpatient settings than in hospitals. Although these data enhance information about error related negligent events in primary care, particularly when combined with other primary care data, there are many operating limitations. PMID:15069219

[Improvement of epirubicin-induced phlebitis to switch from liquid preparation to lyophilized formulation].

PubMed

Suga, Yukio; Kumazaki, Masafumi; Nishigami, Jun; Takeda, Kazuyoshi; Kawagishi, Atsufumi; Ishizaki, Junko; Inokuchi, Masafumi; Miyamoto, Ken-Ichi; Arai, Kunizo

2009-01-01

Adjuvant chemotherapy containing epirubicin is commonly used to treat patients with pre- or post-operative breast cancer. It is known that the epirubicin(FarmorubicinRTU)preparation often caused phlebitis, whereas dexamethasone has been used to prevent that reaction. We examined whether the lyophilized formulation of epirubicin(Farmorubicin)can reduces the incidence of phlebitis compared with the preparation. All infusions were administered through a peripheral vein. Adverse drug reaction including phlebitis was evaluated after each infusion and at the subsequent visit to four or six cycles. Sixty-two patients were given the preparation and 35 the lyophilized formulation. Epirubicininduced phlebitis was observed in 45.7% of patients given the preparation and in 48.4% of those given the lyophilized formulation. There was no statistically significant difference between the two groups(p=0.41). However, the incidence of severe phlebitis requiring treatment with steroid ointment was significantly increased among patients treated with the preparation(27.4% vs 9.7%, p<0.05, respectively). There was no significant difference in the incidence of adverse drug reactions other than severe phlebitis between the two groups. In this study, lyophilized formulations of epirubicin significantly reduced the incidence of severe phlebitis compared with that among patients receiving the preparation. Using lyophilized formulations of epirubicin should be considered to prevent a reduction in QOL with epirubicin-induced phlebitis in patients with breast cancer.

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.

Esophageal triamcinolone acetonide-filling method: a novel procedure to prevent stenosis after extensive esophageal endoscopic submucosal dissection (with videos).

PubMed

Shibagaki, Kotaro; Ishimura, Norihisa; Oshima, Naoki; Mishiro, Tsuyoshi; Fukuba, Nobuhiko; Tamagawa, Yuji; Yamashita, Noritsugu; Mikami, Hironobu; Izumi, Daisuke; Taniguchi, Hideaki; Sato, Shuichi; Ishihara, Shunji; Kinoshita, Yoshikazu

2018-02-01

Endoscopic submucosal dissection (ESD) for extensive esophageal carcinomas may cause severe stenosis requiring endoscopic balloon dilations (EBDs). A standard prevention method has not been established. We propose the esophageal triamcinolone acetonide (TA)-filling method as a novel local steroid administration procedure. We enrolled 22 consecutive patients with early esophageal cancer who were treated using either subcircumferential or circumferential ESD (15 and 7 procedures, respectively) in this case series. Esophageal TA filling was performed on the day after ESD and 1 week later and was performed again if mild stenosis was found on follow-up. EBD with TA filling was performed only for severe stenosis that prevented endoscope passage. The primary endpoint was the incidence of severe stenosis. Secondary endpoints were the total number of EBDs and additional TA filling, dysphagia score, time to stenosis and to complete re-epithelialization, and any adverse events. The incidence of severe stenosis was 4.5% (1/22; confidence interval, .1%-22.8%), and EBD was performed 2 times in 1 patient. Mild stenosis was found in 9 patients. Additional TA filling was performed in 45.5% of patients (10/22; median, 5 times; range, 1-13). The dysphagia score deteriorated to 1 to 2 in 31.8% (7/22) but showed a final score of 0 after complete re-epithelialization in 90.9% (20/22). The median time to stenosis was 3 weeks (range, 3-4) and that to complete re-epithelialization was 7 weeks (range, 4-36). No severe adverse events occurred. The esophageal TA-filling method is highly effective for preventing severe stenosis after extensive esophageal ESD. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model.

PubMed

Beaver, Laura M; Nkrumah-Elie, Yasmeen M; Truong, Lisa; Barton, Carrie L; Knecht, Andrea L; Gonnerman, Greg D; Wong, Carmen P; Tanguay, Robert L; Ho, Emily

2017-05-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring's mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. Published by Elsevier Inc.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model

PubMed Central

Beaver, Laura M.; Nkrumah-Elie, Yasmeen M.; Truong, Lisa; Barton, Carrie L.; Knecht, Andrea L.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

2017-01-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring’s mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. PMID:28268202

[Analysis of Kudiezi injection's security literature].

PubMed

Chang, Yan-Peng; Xie, Yan-Ming

2012-09-01

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

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

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/

Promoting adverse drug reaction reporting: comparison of different approaches.

PubMed

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

2016-01-01

To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. 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. 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). 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.

Reporting of adverse drug reactions in randomised controlled trials – a systematic survey

PubMed Central

Loke, Yoon Kong; Derry, Sheena

2001-01-01

Background Decisions on treatment are guided, not only by the potential for benefit, but also by the nature and severity of adverse drug reactions. However, some researchers have found numerous deficiencies in trial reports of adverse effects. We sought to confirm these findings by evaluating trials of drug therapy published in seven eminent medical journals in 1997. Methods Literature review to determine whether the definition, recording and reporting of adverse drug reactions in clinical trials were in accordance with published recommendations on structured reporting. Results Of the 185 trials reviewed, 25 (14%) made no mention of adverse drug reactions. Data in a further 60 (32%) could not be fully evaluated, either because numbers were not given for each treatment arm (31 trials), or because a generic statement was made without full details (29 trials). When adverse drug reactions such as clinical events or patient symptoms were mentioned in the reports, details on how they had been recorded were given in only 14/95 (15%) and 18/104 (17%) trials respectively. Of the 86 trials that mentioned severity of adverse drug reactions, only 42 (49%) stated how severity had been defined. The median amount of space used for safety data in the Results and Discussion sections was 5.8%. Conclusions Trial reports often failed to provide details on how adverse drug reactions were defined or recorded. The absence of such methodological information makes comparative evaluation of adverse reaction rates potentially unreliable. Authors and journals should adopt recommendations on the structured reporting of adverse effects. PMID:11591227

Osteomyelitis: A rare complication of pancreatitis and PPP-syndrome.

PubMed

Langenhan, Ronny; Reimers, Niklas; Probst, Axel

2016-03-01

Pancreatic diseases can be accompanied by periarthritis with bone necrosis and panniculitis (PPP-syndrome). It is postulated that this is caused by systemic activity of pancreatic enzymes leading to microcirculatory disturbances and fat necrosis. The morbidity and mortality of the PPP-syndrome is high. Successful treatment of pancreatitis can lead to resolution of accompanying panniculitis and periarthritis without adverse sequelae, but weeks or months after pancreatitis, asymptomatic necrosis of the bone may become symptomatic by fracturing spontaneously. In this report, we also describe osteomyelitis as a severe septic complication of bone necrosis caused by pancreatitis, in one case as acute tissue necrosis and in another case months after pancreatitis spread haematogenously. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Consequences of the "back to sleep" program in infants.

PubMed

Miller, Lauren C; Johnson, Arlene; Duggan, Lisa; Behm, Melissa

2011-08-01

Sudden infant death syndrome (SIDS) is the third leading cause of infant mortality in the United States and the leading cause of death among infants 28-364 days of age. The "Back to Sleep" program was implemented in 1992 to promote supine sleeping in efforts to prevent SIDS. Along with this implementation came several consequences that are avoidable in infants. The purposes of this article are to describe the Back to Sleep program and its intended purpose, to identify the adverse consequences, and to develop a teaching program for nurse practitioners to use with parents that will both promote safe sleeping and reduce the untoward consequences of the back to sleep program while maintaining the integrity of the SIDS prevention advice. Copyright © 2011 Elsevier Inc. All rights reserved.

Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes

PubMed Central

Harris, Kathryn; Kamiza, Steve; Harjunmaa, Ulla; Ashorn, Ulla; Nkhoma, Minyanga; Dewey, Kathryn G.; Maleta, Kenneth; Ashorn, Per; Klein, Nigel

2017-01-01

Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy. PMID:28700642

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy.

PubMed

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-09-02

BACKGROUND This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. MATERIAL AND METHODS The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. RESULTS Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. CONCLUSIONS We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy

PubMed Central

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-01-01

Background This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. Material/Methods The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. Results Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. Conclusions We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy. PMID:28864818

A U.S. perspective on the adverse reactions from traditional Chinese medicines.

PubMed

Ko, Richard J

2004-03-01

Traditional Chinese medicines (TCM) are popular in the United States and Asian and non-Asian consumers are using the product for disease treatment and health prevention. As more people are using TCM products, there are increased reports on adverse reactions. This review will focus on adverse reactions due to TCM as reported in the literature. The review is based on MedLine search of literatures using keywords including: herbs, herbal, traditional Chinese medicines with toxicity, adverse effects, death, drug interaction and pharmacokinetic. In addition, specific searches were performed using the above keywords with the common name and the scientific name of the plant product. The causes of adverse reactions associated with TCM are diverse. They include variability in active/toxic ingredients due to growing conditions, use of inherent toxic herbs causing toxicity, overdose of herbs, drug-herb interactions especially with pharmaceuticals that have narrow therapeutic index, coexisting diseases, and idiosyncratic reactions like allergy, hepatitis and anaphylaxis. Other adverse reactions can be due to manufacturing and quality problems causing adulteration, misidentification, substitution of one herb with another, variability in the amount of active ingredients, use of pharmaceuticals without identifying on the labels, improper processing and preparation, and contamination. To minimize the adverse reactions from TCM and protect the public, there must be adequate laws and regulations to ensure that products are manufactured with the highest standards. Manufacturers should be licensed by regulatory agency and manufactured under good manufacturing practice. TCM products must be evaluated for their safety before marketing. Proper labeling and good surveillance systems shall ensure the protection of the consumers.

Dying to be famous: retrospective cohort study of rock and pop star mortality and its association with adverse childhood experiences

PubMed Central

Bellis, Mark A; Hughes, Karen; Sharples, Olivia; Hennell, Tom; Hardcastle, Katherine A

2012-01-01

Objectives Rock and pop fame is associated with risk taking, substance use and premature mortality. We examine relationships between fame and premature mortality and test how such relationships vary with type of performer (eg, solo or band member) and nationality and whether cause of death is linked with prefame (adverse childhood) experiences. Design A retrospective cohort analysis based on biographical data. An actuarial methodology compares postfame mortality to matched general populations. Cox survival and logistic regression techniques examine risk and protective factors for survival and links between adverse childhood experiences and cause of death, respectively. Setting North America and Europe. Participants 1489 rock and pop stars reaching fame between 1956 and 2006. Outcomes Stars’ postfame mortality relative to age-, sex- and ethnicity-matched populations (USA and UK); variations in survival with performer type, and in cause of mortality with exposure to adverse childhood experiences. Results Rock/pop star mortality increases relative to the general population with time since fame. Increases are greater in North American stars and those with solo careers. Relative mortality begins to recover 25 years after fame in European but not North American stars. Those reaching fame from 1980 onwards have better survival rates. For deceased stars, cause of death was more likely to be substance use or risk-related in those with more adverse childhood experiences. Conclusions Relationships between fame and mortality vary with performers’ characteristics. Adverse experiences in early life may leave some predisposed to health-damaging behaviours, with fame and extreme wealth providing greater opportunities to engage in risk-taking. Millions of youths wish to emulate their icons. It is important they recognise that substance use and risk-taking may be rooted in childhood adversity rather than seeing them as symbols of success. PMID:23253869

Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

PubMed Central

de Silva, H. Asita; Pathmeswaran, Arunasalam; Ranasinha, Channa D.; Jayamanne, Shaluka; Samarakoon, Senarath B.; Hittharage, Ariyasena; Kalupahana, Ranjith; Ratnatilaka, G. Asoka; Uluwatthage, Wimalasiri; Aronson, Jeffrey K.; Armitage, Jane M.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

Background Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized. Trial registration www.ClinicalTrials.gov NCT00270777 Please see later in the article for the Editors' Summary PMID:21572992

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

Safety of Bifidobacterium breve (BBG-01) in preterm infants.

PubMed

Kitajima, Hiroyuki; Hirano, Shinya

2017-03-01

Since 1982, viable cells of Bifidobacterium breve (BBG-01) have been used in pediatric patients for clinical conditions such as intractable infantile diarrhea, preterm status, and pediatric surgery. Although the efficacy of BBG-01 has been widely reported, adverse events related to the use of BBG-01 have been reported in very few cases. In order to trace adverse events seen by 109 doctors in 88 medical institutions where BBG-01 was used, a questionnaire survey of the number of occurrences and details of each case was conducted. Eighty-six clinicians (70 institutions) responded to the questionnaire (response rate, 78.9%). Number of respondents according to department of diagnosis (no. BBG-01-treated infants) was as follows: pediatrics, 29 respondents (10 938 patients); premature and newborn medicine, 26 (10 677 patients); obstetrics and gynecology, 1 (1212 patients) and pediatric surgery, 22 (169 patients). More than 90% of the total BBG-01-treated patients (23 092 patients) were in the departments of premature and newborn medicine and pediatrics, and BBG-01 had been used mainly in preterm infants and children with intractable diarrhea. Adverse events occurred in two extremely premature infants with functional ileus due to starch aggregates as vehicle, and in two surgical neonates with bacteremia caused by B. breve genetically identical to BBG-01, and no serious adverse events with poor outcome were reported. Adverse events related to the use of BBG-01 have an extremely low incidence and are mild in severity, thus ensuring the superior safety of this preparation. © 2016 Japan Pediatric Society.

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%).

Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes.

PubMed

Lin, Abigail; Turner, Zahava; Doerrer, Sarah C; Stanfield, Anthony; Kossoff, Eric H

2017-03-01

Many centers still admit children for several days to start the ketogenic diet. The exact incidence of adverse effects during the admission and their potential later impact on seizure reduction has not been widely studied. We performed a retrospective study of children with intractable epilepsy electively admitted for ketogenic diet initiation at our institution from 2011 to 2016. Charts were reviewed for adverse effects during the admission period and then examined for seizure reduction and compliance at three months. A rating scale (1 to 4) was created for severity of any adverse events. A total of 158 children were included, with the mean age 4.6 years. Potentially attributable adverse effects occurred in 126 (80%) children, most commonly emesis, food refusal, and hypoglycemia. Seventy-three (46%) children received some form of intervention by the medical team, most commonly the administration of juice (24%). Younger age was correlated with an increased likelihood of moderate to severe adverse effects during admission, often repeated hypoglycemia (3.6 versus 4.9 years, P = 0.04). Fasting was more likely to result in lethargy and a single blood glucose in the 30 to 40 mg/dL range, but it was not correlated with emesis, repeated hypoglycemia, or higher adverse effect scores. There was no statistically significant correlation between the severity of adverse effects and the three-month seizure reduction. Mild easily treated adverse effects occurred in most children admitted for the ketogenic diet. Younger children were at greater risk for significant difficulties and should be monitored closely. Because fasting led to more lethargy and hypoglycemia, it may be prudent to avoid this in younger children. Copyright © 2017 Elsevier Inc. All rights reserved.

Fluoroquinolones and Tendinopathy: A Guide for Athletes and Sports Clinicians and a Systematic Review of the Literature

PubMed Central

Lewis, Trevor; Cook, Jill

2014-01-01

Context: Fluoroquinolone antibiotics have been used for several decades and are effective antimicrobials. Despite their usefulness as antibiotics, a growing body of evidence has accumulated in the peer-reviewed literature that shows fluoroquinolones can cause pathologic lesions in tendon tissue (tendinopathy). These adverse effects can occur within hours of commencing treatment and months after discontinuing the use of these drugs. In some cases, fluoroquinolone usage can lead to complete rupture of the tendon and substantial subsequent disability. Objective: To discuss the cause, pharmacology, symptoms, and epidemiology of fluoroquinolone-associated tendinopathy and to discuss the clinical implications with respect to athletes and their subsequent physiotherapy. Data Sources: We searched MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), Allied and Complementary Medicine Database (AMED), and SPORTDiscus databases for available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture) published from 1966 to 2012. Search terms were fluoroquinolones or quinolones and tendinopathy, adverse effects, and tendon rupture. Included studies were written in or translated into English. Non—English–language and non-English translations of abstracts from reports were not included (n = 1). Study Selection: Eligible studies were any available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture). Both animal and human histologic studies were included. Any papers not focusing on the tendon-related side effects of fluoroquinolones were excluded (n = 71). Data Extraction: Data collected included any cases of fluoroquinolone-related tendinopathy, the particular tendon affected, type of fluoroquinolone, dosage, and concomitant risk factors. Any data outlining the adverse histologic effects of fluoroquinolones also were collected. Data Synthesis: A total of 175 papers, including 89 case reports and 8 literature reviews, were identified. Conclusions: Fluoroquinolone tendinopathy may not respond well to the current popular eccentric training regimes and may require an alternative, staged treatment approach. Clinicians, athletes, athletic trainers, and their medical support teams should be aware of the need to discuss and possibly discontinue these antibiotics if adverse effects arise. PMID:24762232

Drug therapeutic failures in emergency department patients. A university hospital experience.

PubMed

Franceschi, Alessandro; Tuccori, Marco; Bocci, Guido; Vannozzi, Francesca; Di Paolo, Antonello; Barbara, Cecilia; Lastella, Marianna; Blandizzi, Corrado; Del Tacca, Mario

2004-01-01

Drug therapeutic failure (DTF) could be considered as an adverse drug reaction in which the expected drug effects do not occur following a prescribed pharmacological treatment, including any clinical event that could be related to a low prescribed dose or lack of compliance. DTFs are responsible for increasing disease length, hospitalisation time and social costs, with the worsening of patient quality of life. The aims of the present study are: (1) to estimate the frequency of DTFs among cases of adverse drug events referred to the emergency department; (2) to identify drug classes implicated in DTFs; (3) to analyse the putative causes underlying DTFs. Data presented in this paper were obtained from the Pronto Soccorso and Adverse Drug Events (PSADE) study carried out to analyse drug-related emergency department admissions in several Italian hospitals. Patients, admitted to the emergency department throughout two periods of 10 days each, were interviewed to gain information on their medical status and drug intake during the last two weeks. The present study analysed the patient questionnaires collected in the emergency department of Pisa University Hospital. Among 123 recorded cases of adverse drug event, 41 cases (19:22 male:female ratio; age range: 17-98 years, median age: 75 years) were identified as suspect DTF, resulting in a frequency of 33.33%. A statistical analysis was performed to evaluate the influence of two variables, class of patient age and number of drugs assumed, on DTFs. In accordance with the present findings, showing that the number of drugs assumed by a patient may increase the risk of DTF more than advanced age (odds ratio: 1.371, P<0.02; 1.295, P<0.03, respectively), the prescription of pharmacological combinations might be proposed as a main risk factor for DTF occurrence. In conclusion, our results suggest that DTFs represent an important cause of emergency department admission, particularly in elderly subjects treated with pharmacological associations.

A Case Report of Severe Corneal Toxicity following 0.5% Topical Moxifloxacin Use.

PubMed

Vignesh, A P; Srinivasan, Renuka; Karanth, Swathi

2015-01-01

Moxifloxacin is a widely used topical antibiotic in various bacterial infections of the eye. Its safety and efficacy have been proved by many studies. We report a case of a rare adverse effect following its use. A 10-year-old female who had presented with acute bacterial conjunctivitis in both eyes with no corneal involvement was started on preservative-free 0.5% topical moxifloxacin four times a day. The child developed a severe form of corneal toxicity in both eyes with circumcorneal congestion and corneal edema following its use. The child's visual acuity had dropped from 20/20 to 20/400 in both the eyes. Topical moxifloxacin was discontinued, following which the cornea cleared dramatically and the visual acuity became normal. This case indicates that though rare, topical moxifloxacin can cause severe keratitis and that more studies need to be conducted to evaluate its safety.

Curing genetic disease with gene therapy.

PubMed

Williams, David A

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile.

Curing Genetic Disease with Gene Therapy

PubMed Central

Williams, David A.

2014-01-01

Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile. PMID:25125725

Maternal and fetal plasma zinc in pre-eclampsia.

PubMed

Bassiouni, B A; Foda, A I; Rafei, A A

1979-04-01

Zinc is important for fetal growth and is involved in several important enzyme systems. Maternal and umbilical plasma zinc concentrations were determined in 52 parturient women with mild and severe pre-eclampsia, and were compared with those obtained from 20 women in labor whose pregnancies had progressed normally. A decrease in maternal as well as umbilical plasma zinc concentrations was observed in pre-eclamptic women, and this decrease was statistically significant in severe pre-eclampsia. The causes of these changes in plasma zinc concentrations in pre-eclampsia were discussed, and the possible adverse effects of zinc deficiency on the mother and fetus were mentioned. Low plasma zinc concentrations in pre-eclampsia may be a sign of zinc deficiency, implying possible risks to the mother and her fetus. It is recommended that maintenance of adequate dietary zinc nutrition during pregnancy, and particularly in pre-eclampsia, is important.

Dermoscopic features of nail psoriasis treated with biologics.

PubMed

Hashimoto, Yuki; Uyama, Miki; Takada, Yuko; Yoshida, Kenji; Ishiko, Akira

2017-05-01

Although psoriatic nail lesions are small, they cause considerable discomfort for patients and adversely affect quality of life. Few studies have evaluated the dermoscopic features of psoriatic nails. The aim of this study was to clarify the dermoscopic features of nail psoriasis and identify those that reflect psoriatic activity. During biologic treatment of psoriasis, six patients with psoriatic nails twice underwent dermoscopic examination, with an interval of 17-42 weeks. We used the modified Nail Psoriasis Severity Index score and Psoriasis Area and Severity Index score to identify and assess dermoscopic features. We identified 10 dermoscopic findings, of which disappearance of diffuse scaling of the nail plate, transverse step-like notches and splinter hemorrhages of the nail bed, and appearance of erythematous borders of the onycholytic area were associated with improvement in Psoriasis Area and Severity Index score. Dermoscopy can detect nail changes during psoriasis treatment and should be used to evaluate treatment success. © 2017 Japanese Dermatological Association.

40 CFR 717.1 - Scope and compliance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ACT RECORDS AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO... mixtures: (a) To keep “records of significant adverse reactions to health or the environment, as determined...

40 CFR 717.1 - Scope and compliance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ACT RECORDS AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO... mixtures: (a) To keep “records of significant adverse reactions to health or the environment, as determined...

Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice.

PubMed

Tonello, Raquel; Rigo, Flávia; Gewehr, Camila; Trevisan, Gabriela; Pereira, Elizete Maria Rita; Gomez, Marcus Vinicius; Ferreira, Juliano

2014-06-01

Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids. This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine. Copyright © 2014. Published by Elsevier Inc.

[Research progress of Chinese herbal medicine and traditional Chinese medicine resulting in liver injury].

PubMed

Wang, Jingli; Zhou, Chaofan

2011-12-01

The adverse reactions caused by Chinese herbal medicine and traditional Chinese medicine are reported increased in recent years, among which the acute liver injury caused by Chinese herbal medicine accounts for 21.5% of total liver injuries. Despite the misuse of traditional Chinese medicine not in accordance with differentiation of symptoms and signs, the adverse reaction of Chinese herbal medicine itself can't be little to these adverse events. The paper summarizes the most common categories of traditional Chinese medicine resulting in liver injury, the mechanism, pathological characteristics, clinical symptom of liver injury, the reasons of the reaction and how to prevent. The research aims to enhance the clinical physician recognition of liver injury caused by Chinese herbal medicine, in order to ensure the safe and rational usage of traditional Chinese medicine.

A new fully covered metal stent with anti-migration features for the treatment of malignant dysphagia.

PubMed

Walter, Daisy; van den Berg, Maarten W; van Hooft, Jeanin E; Boot, Henk; Scheffer, Robert C H; Vleggaar, Frank P; Siersema, Peter D

2014-12-01

A new esophageal stent with two anti-migration features was developed to minimize migration. The aim of this study was to evaluate the clinical efficacy and safety of this stent in patients with malignant dysphagia. A total of 40 patients with dysphagia due to a malignant obstruction of the esophagus were prospectively enrolled in this cohort study. Stent placement was technically successful in 39 patients (98 %). The median dysphagia-free time after stent placement was 220 days (95 % confidence interval 94 - 345 days). Nine patients (23 %) experienced recurrent dysphagia due to tissue overgrowth (n = 2), stent fracture (n = 1), and partial (n = 5) or complete (n = 1) stent migration. A total of 16 serious adverse events occurred in 14 patients (36 %), with hemorrhage (n = 3) and severe nausea or vomiting (n = 3) being the most common causes. This new stent design was effective for the palliation of malignant dysphagia and had a low rate of recurrent dysphagia. However, despite the anti-migration features, stent migration was still a major cause of recurrent dysphagia. Furthermore, treatment was associated with a high adverse event rate. Dutch Trial Registration (NTR 3313). © Georg Thieme Verlag KG Stuttgart · New York.

Dermatologic surgery emergencies: Complications caused by systemic reactions, high-energy systems, and trauma.

PubMed

Minkis, Kira; Whittington, Adam; Alam, Murad

2016-08-01

While the overall incidence of emergencies in dermatologic surgery is low, emergent situations can occasionally pose a risk to patients undergoing such procedures. The clinical importance of several types of emergences related to systemic reactions, high energy systems, and trauma are reviewed, and relevant epidemiology, clinical manifestations, diagnosis, work-up, management, and prevention are discussed. Early detection of surgical emergencies can mitigate any associated adverse outcomes, thereby allowing the outstanding record of safety of dermatologic surgery to continue. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Acute Generalized Exanthematous Pustulosis Due to Insect Bites?

PubMed Central

Bhat, Yasmeen J; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Wani, Rohi

2015-01-01

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs and rarely associated with viral infections, food allergens or toxins. Here we present the report of three patients who got admitted in our hospital for generalized pustulosis and fever after insect bites. The diagnosis of acute generalized exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was excluded and spider bite was implicated as the etiological agent in these cases of AGEP which are the first such reported cases in India. PMID:26288442

Liver failure due to antithyroid drugs: report of a case and literature review.

PubMed

Livadas, Sarantis; Xyrafis, Xenofon; Economou, Frangiskos; Boutzios, Georgios; Christou, Maria; Zerva, Aristea; Karachalios, Athanasios; Palioura, Helen; Palimeri, Sotiria; Diamanti-Kandarakis, Evanthia

2010-08-01

Hyperthyroidism is a common endocrine disorder affecting 2% of females and 0.5% of males worldwide and antithyroid drugs constitute the first line of treatment in the majority of cases. These agents may cause severe adverse effects and among them liver failure, although rare, is a potential lethal one. This case illustrates the sudden and abrupt deterioration of hepatic function due to antithyroid drug administration. This case along with a concise literature review is presented aiming to increase the awareness of endocrinologists of possible fatal complications from the everyday use of common agents such as antithyroid drugs.

Emerging therapies for the management of chronic hyperkalemia in the ambulatory care setting.

PubMed

Henneman, Amy; Guirguis, Erenie; Grace, Yasmin; Patel, Dimple; Shah, Bhoomi

2016-01-15

Emerging treatment options for the management of chronic hyperkalemia in the outpatient setting are reviewed. Current treatment options for the management of hyperkalemia are limited and often accompanied by serious adverse effects. Two investigational drugs for the treatment of hyperkalemia are being evaluated in Phase III trials: sodium zirconium cyclosilicate and patiromer. Both of these drugs are administered orally and act by enhancing potassium's removal, predominantly through the gastrointestinal tract. The safety and efficacy of sodium zirconium cyclosilicate and patiromer were evaluated in Phase II and III trials. Both agents were studied in patients with chronic mild-to-severe hyperkalemia, chronic kidney disease (CKD), or heart failure as well as those taking a renin-angiotensin system (RAS) inhibitor, an aldosterone antagonist, or both therapies. These clinical trials found that sodium zirconium cyclosilicate and patiromer normalized serum potassium levels quickly and maintained normalized serum potassium levels over several weeks. Both medications caused a rapid decrease in serum potassium, with two studies examining efficacy endpoints for 12 weeks or longer. The overall frequency of adverse effects in these clinical trials was low, with gastrointestinal adverse events being the most commonly observed. Options for the management of hyperkalemia, particularly chronic hyperkalemia in the outpatient setting, are limited. Both sodium zirconium cyclosilicate and patiromer are emerging therapies that may provide long-term management of hyperkalemia, particularly in patients with underlying heart failure or CKD as well as those taking an RAS inhibitor, an aldosterone antagonist, or both. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis.

PubMed

Ogura, Takashi; Azuma, Arata; Inoue, Yoshikazu; Taniguchi, Hiroyuki; Chida, Kingo; Bando, Masashi; Niimi, Yuka; Kakutani, Shinichi; Suga, Moritaka; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-09-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting. We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data. Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months. This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Allergic reactions to measles-mumps-rubella vaccination.

PubMed

Patja, A; Mäkinen-Kiljunen, S; Davidkin, I; Paunio, M; Peltola, H

2001-02-01

Immunization of egg-allergic children against measles, mumps, and rubella (MMR) is often deferred or even denied, although the safety of this vaccination has been clearly shown. Moreover, the majority of severe allergic reactions have occurred in egg-tolerant vaccinees. Other allergenic vaccine components have been sought, and gelatin has been suggested as one cause of allergic adverse events. The aim of this study was to further characterize the actual allergenic vaccine components. Serum samples from 36 recipients of MMR vaccine with anaphylaxis, urticaria with or without angioedema, asthmatic symptoms, or Henoch-Schönlein purpura were analyzed by CAP System radioallergosorbent test (RAST) and immunospot methods to detect the allergenic vaccine component. To evaluate the correspondence between the findings in the CAP System RAST or the immunospot and clinical symptoms, histories of allergies and present hypersensitivity symptoms were assessed. Of the 36 participants, 10 were demonstrated to be allergic to gelatin. Seven of them had persistent allergic symptoms, possibly attributable to foods containing gelatin or cross-reactive allergens. The results of the immunospot suggested concomitant allergy to gelatin and egg, chicken, and feathers, as well as cow's milk, or they reflected allergen cross-reactivity. Although severe allergic adverse events attributable to MMR vaccination are extremely rare, all serious allergic reactions should be further assessed to detect the likely causative vaccine component, including gelatin. The current recommendation for immunization of egg-allergic persons according to standard MMR vaccination schedules is reinforced. measles, mumps, and rubella vaccine, immunization, adverse effects, allergic reactions, gelatin allergy, CAP System, radioallergosorbent test, immunospot, immunoglobulin E.

Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management.

PubMed

Shen, John; Chang, Jason; Mendenhall, Melody; Cherry, Grace; Goldman, Jonathan W; Kulkarni, Rajan P

2018-01-01

The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with topical corticosteroids and without discontinuation of the systemic treatment.

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

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.

The impact of tobacco use and secondhand smoke on hospitality workers.

PubMed

Siegel, Michael; Barbeau, Elizabeth M; Osinubi, Omowunmi Y

2006-01-01

Tobacco use has a substantial impact on hospitality industry employees because of the disproportionate prevalence of smoking among these workers and because of the high levels of secondhand smoke to which they are exposed. The severity of this impact is evidenced by the high mortality rates observed among hospitality industry workers from diseases related to tobacco smoke exposure. Several states and localities have begun to enact laws to protect these workers from secondhand smoke exposure. Such policies seem to be effective in reducing exposure and improving health among these workers without causing any adverse impact on business. Occupational clinicians can play a significant role in protecting the health of hospitality workers by supporting laws to create smoke-free workplaces, including bars and restaurants, and promoting smoking cessation in these worksites.

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.

Severe hypertriglyceridemia and colchicine intoxication following suicide attempt.

PubMed

Lev, Shaul; Snyder, David; Azran, Carmil; Zolotarsky, Victor; Dahan, Arik

2017-01-01

Colchicine overdose is uncommon but potentially life threatening. Due to its serious adverse systemic effects, overdose must be recognized and treated. We report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg) of colchicine in a suicide attempt. The patient's clinical manifestations included abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and rhabdomyolysis. Two unique manifestations of toxicity in this patient were profound and persistent, severe hypertriglyceridemia and electrolyte imbalance, mainly hypophosphatemia, with no other evident cause except the colchicine intoxication. Following intensive supportive treatment, including ventilator support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte repletion, and zinc supplementation, the patient made a complete recovery. Colchicine intoxication is a severe, life-threatening situation that should be followed closely in intensive care units. Severe changes in body functions can rapidly develop, as previously described in the literature. To our knowledge, this extremely elevated triglyceride level has never been reported without the administration of propofol, and requires further evaluation.

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 challenge of changing the inactivated poliomyelitis vaccine in Latin America: declaration of the Latin American Society of Pediatric Infectious Diseases (SLIPE).

PubMed

Falleiros-Arlant, Luiza Helena; Avila-Agüero, María Luisa; Brea del Castillo, José; Mariño, Cristina

2014-10-01

Even though we have already covered 99% of the path to eradicate poliomyelitis from the world, this disease is still causing paralysis in children. Its eradication means not only the end of wild poliovirus circulation, but vaccine-derived poliovirus circulation as well. Taking into account different factors such as: current epidemiological data, adverse events of the attenuated oral poliomyelitis vaccine (OPV), the availability of an injectable inactivated vaccine (IPV) without the potential of causing the severe adverse events of the oral vaccine (OPV), the efficacy and effectiveness of the IPV in several countries of the world where it has been used for several years, the rationale of changing the vaccination schedule in different Latin American countries; the Latin American Society of Pediatric Infectious Diseases (SLIPE) announces its recommendation of switching to IPV in Latin America, by this Declaration, with an Action Plan for 2014-2015 period as regards vaccination against polio policies in Latin America. 1. The optimal proposed schedule consists of four IPV doses (three doses in the primary schedule plus a booster dose), whether IPV is combined or not with other indicated vaccines in the immunization program of the country. During the OPV to IPV transition phase, an alternative schedule is acceptable; 2. Countries should set optimal strategies in order to maintain and improve vaccination coverage, and implement a nominal immunization registry; 3. Improving the Epidemiological Surveillance of Acute Flaccid Paralysis (AFP) and setting up an environmental surveillance program; 4. Setting up strategies for introducing IPV in National Immunization Programs, such as communicating properly with the population, among others; 5. Bringing scientific societies closer to decision makers; 6. Ensuring optimal supply and prices for IPV introduction; 7. Training vaccination teams; 8. Enhancing the distribution and storing logistics of vaccines. In addition to the scientific evidence, the countries that have not yet decided to switch to IPV should consider the implications of equity and social justice.

Root cause analysis of serious adverse events among older patients in the Veterans Health Administration.

PubMed

Lee, Alexandra; Mills, Peter D; Neily, Julia; Hemphill, Robin R

2014-06-01

Preventable adverse events are more likely to occur among older patients because of the clinical complexity of their care. The Veterans Health Administration (VHA) National Center for Patient Safety (NCPS) stores data about serious adverse events when a root cause analysis (RCA) has been performed. A primary objective of this study was to describe the types of adverse events occurring among older patients (age > or = 65 years) in Department of Veterans Affairs (VA) hospitals. Secondary objectives were to determine the underlying reasons for the occurrence of these events and report on effective action plans that have been implemented in VA hospitals. In a retrospective, cross-sectional review, RCA reports were reviewed and outcomes reported using descriptive statistics for all VA hospitals that conducted an RCA for a serious geriatric adverse event from January 2010 to January 2011 that resulted in sustained injury or death. The search produced 325 RCA reports on VA patients (age > or = 65 years). Falls (34.8%), delays in diagnosis and/or treatment (11.7%), unexpected death (9.9%), and medication errors (9.0%) were the most commonly reported adverse events among older VA patients. Communication was the most common underlying reason for these events, representing 43.9% of reported root causes. Approximately 40% of implemented action plans were judged by local staff to be effective. The RCA process identified falls and communication as important themes in serious adverse events. Concrete actions, such as process standardization and changes to communication, were reported by teams to yield some improvement. However, fewer than half of the action plans were reported to be effective. Further research is needed to guide development and implementation of effective action plans.

Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.

PubMed

Orenstein, Lauren A V; Orenstein, Evan W; Teguete, Ibrahima; Kodio, Mamoudou; Tapia, Milagritos; Sow, Samba O; Levine, Myron M

2012-01-01

Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa. We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed. Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6-73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9-16.4) or premature (median 15.4%, IQR: 10.6-19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5-17.6), with the musculoskeletal system comprising 30%. Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.

Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics.

PubMed

O'Neil, Christine K; Hanlon, Joseph T; Marcum, Zachary A

2012-12-01

Osteoarthritis (OA) is the most common cause of disability in older adults, and although analgesic use can be helpful, it can also result in adverse drug events. To review the recent literature to describe potential adverse drug events associated with analgesics commonly used by older adults with OA. To identify articles for this review, a systematic search of the English-language literature from January 2001 to June 2012 was conducted using PubMed, MEDLINE, EBSCO, and the Cochrane Database of Systematic Reviews for publications related to the medical management of OA. Search terms used were "analgesics," "acetaminophen," "nonsteroidal anti-inflammatory drugs" (NSAIDs), "opioids," "pharmacokinetics," "pharmacodynamics," and "adverse drug events." The search was restricted to those articles that concerned humans aged ≥65 years. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that examined analgesic use in older adults. There are limited data to suggest that non-frail elders are more likely than their younger counterparts to develop acetaminophen-induced hepatotoxicity. However, decreased hepatic phase II metabolism in frail elders may result in increased risk of hepatotoxicity. It is now well established that older adults are at higher risk of NSAID-induced gastrointestinal toxicity and renal insufficiency. Insofar as opioids, the data that suggest an increased risk of falls, fractures, or delirium need to be tempered by the potential risk of inadequately treating severe chronic OA-related pain. Acetaminophen is the mainstay frontline analgesic for treating OA-related pain in older adults. NSAIDs should be limited to short-term use only, and for moderate to severe OA-related pain, opioids may be preferable in individuals without substance abuse or dependence issues. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Cancer in working-age is not associated with childhood adversities.

PubMed

Korpimäki, Sonja K; Sumanen, Markku P T; Sillanmäki, Lauri H; Mattila, Kari J

2010-05-01

Early life events are studied as potential causes of cancer. The objective here was to study childhood adversities in the etiology of cancer. The material comprised a population based random sample of 25 898 individuals among the Finnish working-aged population. In 1998 they were requested through six questions in a postal questionnaire to recall their childhood adversities. The cases consisted of people with cancer diagnosed 2000-2006 and registered in the Finnish Cancer Registry (n = 384). The rest of the sample consisted of cancer-free controls. The most common adversities were prolonged financial difficulties, serious conflicts in the family and someone in the family having been seriously or chronically ill. The cancer patients reported more prolonged financial difficulties and someone seriously or chronically ill in the family. They reported less parental divorce than the controls. The associations were not statistically significant after adjusting for age, sex, education, and health behaviour. Nor was there a significant difference in the total number of childhood adversities between the study group and the controls. On the whole, these cancer patients had not experienced more childhood adversities than the controls. According to our findings, there is no cause to attribute development of cancer in working age to childhood adversities. This information may also give relief to other family members.

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.

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

PubMed

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

2017-06-01

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

Understanding the impact of hypoglycemia on the cardiovascular system

PubMed Central

Davis, Ian Charles; Ahmadizadeh, Ida; Randell, Jacqueline; Younk, Lisa; Davis, Stephen N

2017-01-01

Introduction Hypoglycemia occurs commonly in insulin requiring individuals with either Type 1 or Type 2 Diabetes. Areas Covered This article will review recent information on the pro-inflammatory and pro-atherothrombotic effects of hypoglycemia. Additionally, effects of hypoglycemia on arrhythmogenic potential and arterial endothelial dysfunction will be discussed. Effects of hypoglycemia on cardiovascular morbidity and mortality from large clinical studies in Type 1 and Type 2 DM will also be reviewed. Expert Commentary The relative and absolute risk of severe hypoglycemia leading to death and serious adverse events in both cardiovascular and other organ systems has been highlighted following the publication of recent large clinical trials focused on glucose control and outcomes. It would be helpful if future studies could develop broader end points to include minor and moderate hypoglycemia as well as more robust methods for capturing hypoglycemia contemporaneously with adverse events. In addition, perhaps consideration of including hypoglycemia as a primary outcome, may help identify the possible cause and effect of hypoglycemia on cardiovascular morbidity and mortality. PMID:29109754

Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

PubMed Central

Sørhus, Elin; Incardona, John P; Furmanek, Tomasz; Goetz, Giles W; Scholz, Nathaniel L; Meier, Sonnich; Edvardsen, Rolf B; Jentoft, Sissel

2017-01-01

Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes. DOI: http://dx.doi.org/10.7554/eLife.20707.001 PMID:28117666

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial.

PubMed

Hassall, Oliver W; Thitiri, Johnstone; Fegan, Greg; Hamid, Fauzat; Mwarumba, Salim; Denje, Douglas; Wambua, Kongo; Mandaliya, Kishor; Maitland, Kathryn; Bates, Imelda

2015-03-01

In sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable. When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative. The aim of this study was to assess the safety and efficacy of cord blood transfusion in children with severe anaemia. Between June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya. Of these, 87 children were eligible for our study--ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months). Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination. Red blood cells were stored vertically at 2-6°C to enable sedimentation. After transfusion, children were monitored closely for adverse events and followed up for 28 days. The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion. Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels. This trial is registered on ISRCTN.com, number ISRCTN66687527. Of the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion. Therefore, 55 children received umbilical cord red blood cells from 74 donations. Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10). An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97·5% CI 0-6·5). Haemoglobin increased by a median of 26 g/L (IQR 21-31) 24 h after transfusion and by 50 g/L (10-68) a median of 29 days (28-35) after transfusion. These preliminary data suggest that cord blood could be an important supplementary source of blood for transfusion in children in sub-Saharan Africa. Further studies are needed to compare the safety and efficacy of cord blood with conventional adult-donated blood for transfusions. Challenges associated with cost, infrastructure, and scale up also need investigating. Wellcome Trust. Copyright © 2015 Hassall et al. Open access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial

PubMed Central

Hassall, Oliver W; Thitiri, Johnstone; Fegan, Greg; Hamid, Fauzat; Mwarumba, Salim; Denje, Douglas; Wambua, Kongo; Mandaliya, Kishor; Maitland, Kathryn; Bates, Imelda

2015-01-01

Summary Background In sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable. When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative. The aim of this study was to assess the safety and efficacy of cord blood transfusion in children with severe anaemia. Methods Between June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya. Of these, 87 children were eligible for our study—ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months). Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination. Red blood cells were stored vertically at 2–6°C to enable sedimentation. After transfusion, children were monitored closely for adverse events and followed up for 28 days. The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion. Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels. This trial is registered on ISRCTN.com, number ISRCTN66687527. Findings Of the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion. Therefore, 55 children received umbilical cord red blood cells from 74 donations. Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10). An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97·5% CI 0–6·5). Haemoglobin increased by a median of 26 g/L (IQR 21–31) 24 h after transfusion and by 50 g/L (10–68) a median of 29 days (28–35) after transfusion. Interpretation These preliminary data suggest that cord blood could be an important supplementary source of blood for transfusion in children in sub-Saharan Africa. Further studies are needed to compare the safety and efficacy of cord blood with conventional adult-donated blood for transfusions. Challenges associated with cost, infrastructure, and scale up also need investigating. Funding Wellcome Trust. PMID:26687795

Vertigo/dizziness as a Drugs' adverse reaction.

PubMed

Chimirri, Serafina; Aiello, Rossana; Mazzitello, Carmela; Mumoli, Laura; Palleria, Caterina; Altomonte, Mariolina; Citraro, Rita; De Sarro, Giovambattista

2013-12-01

Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs' classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly in fragile patients.

Vertigo/dizziness as a Drugs’ adverse reaction

PubMed Central

Chimirri, Serafina; Aiello, Rossana; Mazzitello, Carmela; Mumoli, Laura; Palleria, Caterina; Altomonte, Mariolina; Citraro, Rita; De Sarro, Giovambattista

2013-01-01

Introduction: Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. Materials and Methods: The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Results: Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Conclusions: Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs’ classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly in fragile patients. PMID:24347974

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

PubMed Central

Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

2011-01-01

Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

PubMed

Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

2012-06-01

Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Influence of root-knot nematode infestation on antioxidant enzymes, chlorophyll content and growth in Pogostemon cablin (Blanco) Benth.

PubMed

Bhau, B S; Borah, Bitupon; Ahmed, Reshma; Phukon, P; Gogoi, Barbi; Sarmah, D K; Lal, M; Wann, S B

2016-04-01

Plants adapt themselves to overcome adverse environmental conditions, and this involves a plethora of concurrent cellular activities. Physiological experiments or metabolic profiling can quantify this response. Among several diseases of Pogostemon cablin (Blanco) Benth. (Patchouli), root-knot nematode infection caused by Meloidogyne incognita (Kofoid and White) Chitwood causes severe damage to the plant and hence, the oil production. In the present study, we identified M. incognita morphologically and at molecular level using sequenced characterized amplified region marker (SCAR). M. incognita was artificially inoculated at different levels of second stage juveniles (J₂) to examine the effect on Patchouli plant growth parameters. Peroxidase and polyphenol oxidase enzyme activity and changes in the total phenol and chlorophyll contents in M. incognita was also evaluated in response to infection. The results have demonstrated that nematode infestation leads to increased peroxidase activities in the leaves of the patchouli plants and thereby, increase in phenolic content as a means of defence against nematode infestation. Chlorophyll content was also found decreased but no changes in polyphenol oxidase enzyme activity.

[A case of acute pancreatitis caused by 5-aminosalicylic acid suppositories in a patient with ulcerative colitis].

PubMed

Kim, Kook Hyun; Kim, Tae Nyeun; Jang, Byung Ik

2007-12-01

Oral 5-aminosalicylic acid (5-ASA) has been known as a first-choice drug for ulcerative colitis. However, hypersensitivity reactions, including pancreatitis, hepatitis, and skin rash, have been reported with 5-ASA. Topical formulations of 5-ASA like suppositories have been rarely reported to induce adverse reactions because of their limited absorption rate. We recently experienced a case of acute pancreatitis caused by 5-ASA suppositories in a patient with ulcerative colitis. A 26-year-old male was admitted with abdominal pain and diagnosed as ulcerative colitis. Acute pancreatitis occurred soon after 24 hours of treatment with oral mesalazine. Drug-induced pancreatitis was suspected and administration of mesalazine was discontinued. Then 5-ASA suppositories were started instead of oral mesalazine. Twenty-four hours after taking 5-ASA suppositories, he experienced severe abdominal pain, fever, and elevation of amylase levels. The suppositories were immediately stopped and symptoms resolved over next 48 hours. Herein, we suggest that, in patients treated with 5-ASA suppositories who complain of severe abdominal pain, drug-induced pancreatitis should be suspected.

Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome.

PubMed

Tandon, Rajiv; Jibson, Michael D

2002-06-01

Previously, clinicians worked with antipsychotic drugs (conventional or typical) that almost invariably caused extrapyramidal symptoms (EPS) at clinically effective doses. This led to the false impression that all antipsychotics were the same, and that EPS were an unavoidable consequence of effective antipsychotic therapy. EPS adversely impact several aspects of antipsychotic efficacy and tolerability, thereby worsening outcome of afflicted individuals. EPS reduce beneficial effects of antipsychotic treatment on the negative, cognitive, and mood symptom domains, while increasing the risk of tardive dyskinesia and reducing compliance. By definition, the newer generation of "atypical" antipsychotic agents are significantly better than conventional agents with regard to EPS (i.e., they are clinically effective at doses at which they do not cause EPS). Pharmacologically, this difference is expressed in the greater degree of separation between respective dose response curves for antipsychotic and EPS effects observed for "atypical" in contrast to conventional agents. Clinically, this EPS advantage of atypical antipsychotics translates into several important benefits, including better negative symptom efficacy, less dysphoria, less impaired cognition, a lower risk of TD, and better overall outcome.

Mitral Regurgitation Severity and Left Ventricular Systolic Dimension Predict Survival in Young Cavalier King Charles Spaniels.

PubMed

Reimann, M J; Møller, J E; Häggström, J; Martinussen, T; Zatrazemi, S S C; Svanholm, L; Nielsen, L B M; Pedersen, H D; Olsen, L H

2017-07-01

Development and progression of myxomatous mitral valve disease (MMVD) in dogs are difficult to predict. Identification at a young age of dogs at high risk of adverse outcome in the future is desirable. To study the predictive value of selected clinical and echocardiographic characteristics associated with MMVD obtained at a young age for prediction of long-term cardiac and all-cause mortality in Cavalier King Charles Spaniels (CKCS). 1125 privately owned CKCS. A retrospective study including CKCS examined at the age of 1-3 years. Long-term outcome was assessed by telephone interview with owners. The value of variables for predicting mortality was investigated by Cox proportional hazard and Kaplan-Meier analyses. Presence of moderate to severe mitral regurgitation (MR) (hazard ratio (HR) = 3.03, 95% confidence interval (95% CI) = 1.48-6.23, P = 0.0025) even intermittent moderate to severe MR (HR = 2.23, 95% CI = 1.48-6.23, P = 0.039) on color flow Doppler echocardiography was significantly associated with increased hazard of cardiac death. An interaction between MR and sex was significant for all-cause mortality (P = 0.035), showing that males with moderate to severe MR had a higher all-cause mortality compared to males with no MR (HR = 2.38, 95% CI = 1.27-4.49, P = 0.0071), whereas no difference was found between female MR groups. The risk of cardiac (HR = 1.37, 95% CI = 1.14-1.63, P < 0.001) and all-cause (HR = 1.13, 95% CI = 1.02-1.24, P = 0.016) mortality increased with increasing left ventricular end-systolic internal dimension normalized for body weight (LVIDS N ). Moderate to severe MR, even if intermittent, and increased LVIDS N in dogs <3 years of age were associated with cardiac death later in life in CKCS. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Role of inflammation in cardiopulmonary health effects of PM

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

Donaldson, Ken; Mills, Nicholas; MacNee, William

2005-09-01

The relationship between increased exposure to PM and adverse cardiovascular effects is well documented in epidemiological studies. Inflammation in the lungs, caused by deposited particles, can be seen as a key process that could mediate adverse effects on the cardiovascular system. There are at least three potential pathways that could lead from pulmonary inflammation to adverse cardiovascular effects. Firstly, inflammation in the lung could lead to systemic inflammation, which is well known to be linked to sudden death from cardiovascular causes. Systemic inflammation can lead to destabilization by activation of inflammatory processes in atheromatous plaques. Secondly, inflammation can cause anmore » imbalance in coagulation factors that favor propagation of thrombi if thrombosis is initiated. Thirdly, inflammation could affect the autonomic nervous system activity in ways that could lead to alterations in the control of heart rhythm which could culminate in fatal dysrhythmia.« less

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.

14 CFR § 1263.108 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Procedure in the event of an adverse ruling. § 1263.108 Section § 1263.108 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... event of an adverse ruling. If the court or other authority which caused the demand to be issued...

Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe vasospasm: preliminary results.

PubMed

Sherif, Camillo; Wambacher, Bernhard; Loyoddin, Michel; Karaic, Radenko; Krafft, Peter; Valentin, Andreas; Tscholakoff, Dimiter; Kleinpeter, Guenther

2015-01-01

Delayed vasospasm (VSP) following aneurysmal subarachnoid hemorrhage (aSAH) remains a major source of morbidity. Milrinone was recently suggested as an invasive VSP treatment option. It is a phosphodiesterase III inhibitor with vasodilating and additional positive inotrope and anti-inflammatory effects. In this preliminary series, we included patients with severe VSP and unsuccessful maximum conservative therapy. Inclusion criteria were (1) transcranial Doppler (TCD) mean >180 cm/s; (2) increase of >50 % of TCD mean values within 6 h to values >150 cm/s; and/or (3) neurological deterioration (after exclusion of hemorrhage, hydrocephalus, and other systemic reasons). Patients received endovascular therapy with nimodipine 2 mg followed by milrinone 4-8 mg. Reinterventions were indicated aggressively in cases of persistent neurological deficits or persistent high mean TCD >180 cm/s. Of 121 consecutive aSAH patients, 16 (13.2 %) received endovascular VSP therapy. Of these, 11 patients (68.5 %) received ≥ 3 interventions (median 4; maximum 9); 14 (87.5 %) showed postinterventional angiographic improvement of vessel diameters; and 11 (68.5 %) showed improvement of their neurological deficits after a mean follow-up time of 4.5 months. No cardiovascular adverse events attributed to milrinone were observed. Milrinone may be a useful supplementary substance for endovascular VSP therapy. Aggressive reintervention indications did not cause additional adverse events.

[Beta blockers in heart failure therapy with special reference to the COPERNICUS Study].

PubMed

Hartmann, Franz; Katus, Hugo A

2002-08-01

During the past 15 years, the pathophysiological concept of heart failure as a neurohormonal disease has influenced heart failure therapy substantially. ACE-inhibitors have become the mainstay of heart failure therapy. In addition, beta blocker evolved to be effective in improving survival in this disease. Recently, the COPERNICUS study established the efficacy of carvedilol in severe heart failure and extended the benefits of this drug first observed in patients with mild and moderate symptoms to those with advanced disease. In this study, carvedilol resulted in a significant reduction of all-cause mortality and combined mortality and hospitalization, the frequency of hospitalizations, the risk of repeated hospitalizations, the number of days in hospital, the average duration of each admission and the utilization of treatments and procedures for heart failure. Carvedilol was well tolerated, improved the sense of well-being, was associated with a lower risk of a serious adverse event, particularly one related to the progression of heart failure and fewer patients requiring withdrawal of treatment for an adverse event. These favourable results were equally seen in all subgroups. Carvedilol treatment was even cost-effective in severe disease. Therefore, this new therapeutic option should be available to all patients with symptomatic systolic heart failure.

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.

Anemia of Inflammation: A Review

PubMed Central

Fraenkel, Paula G.

2016-01-01

Impaired iron homeostasis and the suppressive effects of proinflammatory cytokines on erythropoiesis, together with alterations of the erythrocyte membrane that impair its survival, cause the anemia of inflammation. Recent epidemiologic studies have connected inflammatory anemia with critical illness, obesity, aging, and kidney failure, as well as with cancer, chronic infection, and autoimmune disease. The proinflammatory cytokine, interleukin-6, the iron regulatory hormone, hepcidin, and the iron exporter, ferroportin, interact to cause iron sequestration in the setting of inflammation. While severe anemia is associated with adverse outcomes in critical illness, experimental models suggest that iron sequestration is part of a natural defense against pathogens. In animal models and human patients, experimental therapeutic approaches targeting interleukin-6 or the ferroportin-hepcidin axis have shown efficacy in reversing anemia, although these agents have not yet been approved for the treatment of the anemia of inflammation. PMID:28189171

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis

PubMed Central

Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2013-01-01

Introduction: Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. Materials and Methods: We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. Results: A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected. Conclusions: Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed. PMID:24347984

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.

[Analysis on the adverse events of cupping therapy in the application].

PubMed

Zhou, Xin; Ruan, Jing-wen; Xing, Bing-feng

2014-10-01

The deep analysis has been done on the cases of adverse events and common injury of cupping therapy encountered in recent years in terms of manipulation and patient's constitution. The adverse events of cupping therapy are commonly caused by improper manipulation of medical practitioners, ignoring contraindication and patient's constitution. Clinical practitioners should use cupping therapy cautiously, follow strictly the rules of standard manipulation and medical core system, pay attention to the contraindication and take strict precautions against the occurrence of adverse events.

[Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System].

PubMed

Cuena Boy, R; Maciá Martínez, M A

1998-03-31

To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. Observational, longitudinal, retrospective and comparative study of two series of cases. The entire Spanish healthcare system. Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. None. 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021). There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.

Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

PubMed

Krejci, Charlene B; Bissada, Nabil F

2012-01-01

To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.

PubMed

Mariën, Joachim; Borremans, Benny; Gryseels, Sophie; Soropogui, Barré; De Bruyn, Luc; Bongo, Gédéon Ngiala; Becker-Ziaja, Beate; de Bellocq, Joëlle Goüy; Günther, Stephan; Magassouba, N'Faly; Leirs, Herwig; Fichet-Calvet, Elisabeth

2017-04-27

In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.

Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

PubMed Central

Chen, Robert; O'Connor, Owen A.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Matous, Jeffrey V.; Fasanmade, Adedigbo A.; Manley, Thomas J.; Han, Tae H.

2016-01-01

Abstract Aims Brentuximab vedotin, an antibody–drug conjugate (ADC), selectively delivers the microtubule‐disrupting agent monomethyl auristatin E (MMAE) into CD30‐expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30‐positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment. Methods Systemic exposures were evaluated following intravenous administration of 1.2 mg kg–1 brentuximab vedotin in patients with CD30‐positive haematologic malignancies and hepatic (n = 7) or renal (n = 10) impairment and compared with those of unimpaired patients (n = 8) who received 1.2 mg kg–1 brentuximab vedotin in another arm of the study. Results For any hepatic impairment, the ratios of geometric means (90% confidence interval) for AUC(0,∞) were 0.67 (0.48, 0.93) for ADC and 2.29 (1.27, 4.12) for MMAE. Mild or moderate renal impairment caused no apparent change in ADC or MMAE exposures. Severe renal impairment (creatinine clearance <30 ml min–1; n = 3) decreased ADC exposures (0.71 [0.54, 0.94]) and increased MMAE exposures (1.90 [0.85, 4.21]). No consistent pattern of specific adverse events was evident, but analysis of the safety data was confounded by the patients' poor baseline conditions. Five patients died due to adverse events considered unrelated to brentuximab vedotin. All had substantial comorbidities and most had poor baseline performance status. Conclusions Hepatic impairment and severe renal impairment may cause decreases in brentuximab vedotin ADC exposures and increases in MMAE exposures. PMID:27115790

Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes

PubMed Central

Enas, Enas A.; Kuruvila, Arun; Khanna, Pravien; Pitchumoni, C.S.; Mohan, Viswanathan

2013-01-01

Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians. PMID:24434254

Our current approach to root cause analysis: is it contributing to our failure to improve patient safety?

PubMed

Kellogg, Kathryn M; Hettinger, Zach; Shah, Manish; Wears, Robert L; Sellers, Craig R; Squires, Melissa; Fairbanks, Rollin J

2017-05-01

Despite over a decade of efforts to reduce the adverse event rate in healthcare, the rate has remained relatively unchanged. Root cause analysis (RCA) is a process used by hospitals in an attempt to reduce adverse event rates; however, the outputs of this process have not been well studied in healthcare. This study aimed to examine the types of solutions proposed in RCAs over an 8-year period at a major academic medical institution. All state-reportable adverse events were gathered, and those for which an RCA was performed were analysed. A consensus rating process was used to determine a severity rating for each case. A qualitative approach was used to categorise the types of solutions proposed by the RCA team in each case and descriptive statistics were calculated. 302 RCAs were reviewed. The most common event types involved a procedure complication, followed by cardiopulmonary arrest, neurological deficit and retained foreign body. In 106 RCAs, solutions were proposed. A large proportion (38.7%) of RCAs with solutions proposed involved a patient death. Of the 731 proposed solutions, the most common solution types were training (20%), process change (19.6%) and policy reinforcement (15.2%). We found that multiple event types were repeated in the study period, despite repeated RCAs. This study found that the most commonly proposed solutions were weaker actions, which were less likely to decrease event recurrence. These findings support recent attempts to improve the RCA process and to develop guidance for the creation of effective and sustainable solutions to be used by RCA teams. 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/.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Choi, Ji-Young; Paik, Doo-Jin; Kwon, Dae Young; Park, Yongsoon

2014-04-22

The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/μL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

Taenia ovis: an emerging threat to the Chinese sheep industry?

PubMed

Zheng, Yadong

2016-07-26

Taenia ovis is a tapeworm that is mainly transmitted between dogs and sheep. Although T. ovis infection is not a public health issue, it causes a great financial loss due to condemnation of carcasses.  The first outbreak of T. ovis infection in China occurred in 2015. Reassessment of adverse effects of T. ovis infection on Chinese sheep industry in future is necessary. The first T. ovis outbreak in China suggests that the epidemic situation across the country is underestimated. For the transmission of T. ovis, many factors, including eggs, dogs and wild canids, human behaviours and sheep trade, should be seriously considered. In blocking the transmission chain, regular treatments of the infected dogs using anthelmintics play a crucial step, but at the moment it is difficult to be fully executed in China, largely due to the behaviours, customs and faith of local farmers. Moreover, combined with no clinical symptoms in the infected adult sheep and goats, the lack of pre-mortem diagnostic tools makes it harder to practice a national wide surveillance as well as inspection and quarantine in increasingly frequent free sheep trade activities in China, leading to an inability to restrict T. ovis infection into small areas. Furthermore, the ongoing campaigns against Echinococcus granulosus may have an adverse effect on control of T. ovis infection because of no consideration of a role of dogs in the transmission of the parasite. Lack of national epidemic data, pre-mortem diagnostic reagents and vaccines severely hampers the implementation of disease control campaigns and the restriction of T. ovis infection into small areas. Consequently, sheep and goats are at an increasing risk of T. ovis exposure and the possibility of large-scale outbreaks across China in future is possible, causing great adversity towards sheep industry.

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.

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

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

PubMed Central

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

2010-01-01

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

Worsening psychosis induced by varenicline in a hospitalized psychiatric patient.

PubMed

DiPaula, Bethany A; Thomas, Michele D

2009-07-01

Varenicline is a novel treatment for smoking cessation; however, the agent has not been well studied in a population with severe mental illness. Varenicline can reportedly cause neuropsychiatric adverse effects, some resulting in hospitalizations and/or suicides. We describe a case of clinician-observed, worsening psychotic symptoms in a patient with chronic mental illness who was receiving varenicline. A 45-year-old woman with bipolar disorder, mixed type with psychotic features, was admitted to a psychiatric hospital due to acute decompensation after she discontinued her drug therapy. Because of the facility's smoke-free policy, the patient was not permitted to smoke cigarettes during her hospitalization. Over the next several weeks, her condition was stabilized with psychotropic drugs. Her symptoms improved, and plans were made for her discharge. Varenicline was prescribed to manage her nicotine cravings. After 2 days of treatment, staff members noted worsening of the patient's psychotic symptoms and agitation. Varenicline was discontinued, the patient's mental status returned to baseline, and she was subsequently discharged. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's worsening psychosis and her varenicline therapy. This case report provides valuable support of previously published cases that demonstrate the risk of exacerbation of psychotic symptoms with varenicline use in patients with severe mental illness. With proper assessment and management of varenicline-induced neuropsychiatric effects, health care professionals can provide an important role in helping to prevent and manage worsening psychiatric symptoms.

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.

PubMed

England, Timothy J; Sprigg, Nikola; Alasheev, Andrey M; Belkin, Andrey A; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M

2016-11-15

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

Feline Toxoplasmosis: Tumor Necrosis Factor, Nitric Oxide, and Free Radicals in Seropositive Cats.

PubMed

Faria, Joice L M; Couto, Caroline do; Wierzynski, Sheron L; Bottari, Nathieli B; Baldissera, Matheus D; Pereira, Wanderson A B; Da Silva, Aleksandro S

2018-02-01

Toxoplasma gondii is a cosmopolitan protozoan that causes disease in several species, including humans. In cats, these infections are usually asymptomatic, but in other species they can lead to high levels of inflammatory and cell damage markers, causing cellular damage. Therefore, the aim of this study was to measure levels of tumor necrosis factor (TNF-α), reactive oxygen species (ROS), and nitric oxide (nitrite/nitrate-NO x ) in the serum of cats seropositive for T. gondii. Initially, we investigated the presence of antibodies against T. gondii in cats in the city of Concordia, Santa Catarina, Brazil, with the use of indirect immunofluorescence (IFA), and found 30 cats seropositive for T. gondii and 30 seronegative cats. In this study, seropositive cats showed higher levels of TNF-α, ROS, and NO x compared to seronegative cats. Although cats do not show clinical signs of disease, constant inflammatory response can cause cell damage, which over time may adversely affect the animal.

Resurgence of cholera in Hong Kong.

PubMed Central

Lee, S. H.; Lai, S. T.; Lai, J. Y.; Leung, N. K.

1996-01-01

Cholera is one of the three diseases subject to the International Health Regulations. After a period of over 30 years, the seventh pandemic of cholera, which started in South East Asia in 1961, still shows no sign of a decline. On the contrary, it has increased its severity and invaded many other countries in Africa and Latin America. In the last two years, there has been a recrudescence of the disease in South East Asia and Western Pacific Regions. The discovery of a new strain of Vibrio cholerae 0139 in these regions is causing concern in view of its potential to cause major epidemics and higher mortality. Hong Kong had two intensive outbreaks of cholera in the last two years. The cause of these outbreaks was not clear, but adverse environmental conditions and increasing pollution of coastal waters have been implicated. The spread of cholera knows no geographical boundaries. There is a need for intensified efforts among health authorities in the affected areas to prevent the international spread of the disease. PMID:8760949

Colour-causing defects and their related optoelectronic transitions in single crystal CVD diamond.

PubMed

Khan, R U A; Cann, B L; Martineau, P M; Samartseva, J; Freeth, J J P; Sibley, S J; Hartland, C B; Newton, M E; Dhillon, H K; Twitchen, D J

2013-07-10

Defects causing colour in nitrogen-doped chemical vapour-deposited (CVD) diamond can adversely affect the exceptional optical, electronic and spintronic properties of the material. Several techniques were used to study these defects, namely optical absorption spectroscopy, thermoluminescence (TL) and electron paramagnetic resonance (EPR). From our studies, the defects causing colour in nitrogen-doped CVD diamond are clearly not the same as those causing similar colour in natural diamonds. The brown colour arises due to a featureless absorption profile that decreases in intensity with increasing wavelength, and a broad feature at 360 nm (3.49 eV) that scales in intensity with it. Another prominent absorption band, centred at 520 nm (2.39 eV), is ascribed to the neutral nitrogen-vacancy-hydrogen defect. The defects responsible for the brown colour possess acceptor states that are 1.5 eV from the valence band (VB) edge. The brown colour is removed by heat treatment at 1600 ° C, whereupon new defects possessing shallow (<1 eV) trap states are generated.

[Prevention and treatment of post-traumatic pancreatic necrosis in patients with blunt abdominal trauma].

PubMed

Cherdantsev, D V; Pervova, O V; Vinnik, Iu S; Kurbanov, D Sh

2016-01-01

High incidence of necrotic and suppurative complications is feature of acute post-traumatic pancreatitis. Severe trauma of the pancreas and post-traumatic pancreatitis lead to depressurization of ductal system that requires adequate drainage of damaged area and retroperitoneal fat. 95 patients in group 1 received standardized treatment. The victims of the 2nd group (44 patients) were treated using immunoreactive therapy (roncoleukin) and octreotide (the dose depended on the severity of pancreatitis) at early stages. The efficacy of treatment was assessed based on clinical, laboratory and instrumental parameters. Regardless severity of pancreatic injury overall mortality in groups 1 and 2 was 41% and 20.5% respectively. The main causes of adverse outcomes are severe destructive pancreatitis, postnecrotic suppurative complications. Adequacy rather radicalism of surgery should be preferred for blunt pancreatic trauma management. Minimally invasive surgical techniques and new methods of biological hemostasis may be applied. Timely use of anti-enzymatic and immunoactive therapy reduces the risk of severe post-traumatic pancreatitis, suppurative complications and improves outcomes in patients with blunt pancreatic trauma.

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.

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5.

PubMed

Jalali, Subhadra; Balakrishnan, Divya; Zeynalova, Zarifa; Padhi, Tapas Ranjan; Rani, Padmaja Kumari

2013-07-01

To report serious adverse events and long-term outcomes of initial experience with intraocular bevacizumab in retinopathy of prematurity (ROP). Consecutive vascularly active ROP cases treated with bevacizumab, in addition to laser and surgery, were analysed retrospectively from a prospective computerised ROP database. Primary efficacy outcome was regression of new vessels. Secondary outcomes included the anatomic and visual status. Serious systemic and ocular adverse events were documented. 24 ROP eyes in 13 babies, received single intraocular bevacizumab for severe stage 3 plus after failed laser (seven eyes), stage 4A plus (eight eyes), and stage 4B/5 plus (nine eyes). Drug was injected intravitreally in 23 eyes and intracamerally in one eye. New vessels regressed in all eyes. Vision salvage in 14 of 24 eyes and no serious neurodevelopmental abnormalities were noted up to 60 months (mean 30.7 months) follow-up. Complications included macular hole and retinal breaks causing rhegmatogenous retinal detachment (one eye); bilateral, progressive vascular attenuation, perivascular exudation and optic atrophy in one baby, and progression of detachment bilaterally to stage 5 in one baby with missed follow-up. One baby who received intracameral injection developed hepatic dysfunction. One eye of this baby also showed a large choroidal rupture. Though intraocular bevacizumab, along with laser and surgery salvaged vision in many otherwise progressive cases of ROP, vigilance and reporting of serious adverse events is essential for future rationalised use of the drug. We report one systemic and four ocular adverse events that require consideration in future use of the drug.

Epidemiology of Adverse Events and Medical Errors in the Care of Cardiology Patients.

PubMed

Ohta, Yoshinori; Miki, Izumi; Kimura, Takeshi; Abe, Mitsuru; Sakuma, Mio; Koike, Kaoru; Morimoto, Takeshi

2016-11-02

There have been epidemiological studies of adverse events (AEs) among general patients but those of patients cared by cardiologist are not well scrutinized. We investigated the occurrence of AEs and medical errors (MEs) among adult patients with cardiology in Japan. We conducted a cross-sectional study of adult outpatients at a Japanese teaching hospital from February through November 2006. We measured AE and ME incidents from patient report, which were verified by medical records, laboratory data, incident reports, and prescription queries. Two independent physicians reviewed the incidents to determine whether they were AEs or MEs and to assess severity and symptoms. We identified 144 AEs and 30 MEs (16.3 and 3.9 per 100 patients, respectively). Of the 144 AEs, 99 were solely adverse drug events (ADEs), 20 were solely non-ADEs, and the remaining 25 were both causes. The most frequent symptoms of ADEs were skin and allergic reactions due to medication. The most frequent symptoms of non-ADEs were bleeding due to therapeutic interventions. Among AEs, 12% was life threatening. Life-threatening AEs were 25% of non-ADEs and 5% of ADEs (P = 0.0003). Among the 30 MEs, 21MEs (70%) were associated with drugs. Adverse events were common among cardiology patients. Adverse drug events were the most frequent AEs, and non-ADEs were more critical than ADEs. Such data should be recognized among practicing physicians to improve the patients' outcomes.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Fusion of nonclinical and clinical data to predict human drug safety.

PubMed

Johnson, Dale E

2013-03-01

Adverse drug reactions continue to be a major cause of morbidity in both patients receiving therapeutics and in drug R&D programs. Predicting and possibly eliminating these adverse events remains a high priority in industry, government agencies and healthcare systems. With small molecule candidates, the fusion of nonclinical and clinical data is essential in establishing an overall system that creates a true translational science approach. Several new advances are taking place that attempt to create a 'patient context' mechanism early in drug research and development and ultimately into the marketplace. This 'life-cycle' approach has as its core the development of human-oriented, nonclinical end points and the incorporation of clinical knowledge at the drug design stage. The next 5 years should witness an explosion of what the author views as druggable and safe chemical space, pharmacosafety molecular targets and the most important aspect, an understanding of unique susceptibilities in patients developing adverse drug reactions. Our current knowledge of clinical safety relies completely on pharmacovigilance data from approved and marketed drugs, with a few exceptions of drugs failing in clinical trials. Massive data repositories now and soon to be available via cloud computing should stimulate a major effort in expanding our view of clinical drug safety and its incorporation into early drug research and development.

Review of liver injury associated with dietary supplements.

PubMed

Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

2011-05-01

Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. © 2011 John Wiley & Sons A/S.

[Use of intravenous iron infusion in a gastroenterology day hospital: Indications, dosage and adverse effects].

PubMed

Dosal, Angelina; Calvet, Xavier; Moreno, Laura; López, María; Figuerola, Ariadna; Ruíz, Miquel Angel; Suárez, David; Gené, Emili; Miquel, Mireia; Villoria, Albert

2010-01-01

There are no data in the literature on the use of intravenous iron infusion in gastroenterology day hospitals. To determine the indications, dosage and tolerance of intravenous iron infusion in outpatients attending a gastroenterology day hospital. We retrospectively reviewed the medical records of patients who received intravenous iron infusion between August 2007 and July 2008. The indications, dosage, transfusion requirements, adverse effects and patients' clinical and laboratory data were recorded. During the study period, 111 patients (41% women, with a mean age of 63.8 ± 18 years) received intravenous iron infusions. The main causes of anemia indicating iron administration were portal hypertensive gastropathy (n=55), inflammatory bowel disease (n=22) and intestinal angiodysplasia (n=12). The patients received a total of 557 iron infusions with a mean dose of 1033 mg iron per patient. There were no adverse effects. Despite the treatment, 46 patients required transfusion. Iron and transfusion requirements and mortality were significantly higher in patients with liver cirrhosis than in the remainder of the study group. Intravenous iron therapy is frequently used in the gastroenterology day hospital. Most infusions were administered in patients with chronic iron loss. Patients with liver cirrhosis had the most severe anemia and underlying disease and the highest mortality.

Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis

NASA Astrophysics Data System (ADS)

Liu, Wei; Wu, Yuan-Hao; Zhang, Lei; Liu, Xiao-Ya; Bin Xue; Bin Liu; Wang, Yi; Ji, Yang

2016-09-01

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-α (TNF-α) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-α inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-α inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta-analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-α inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers.

Severe respiratory depression and bradycardia before induction of anesthesia and onset of Takotsubo cardiomyopathy after cardiopulmonary resuscitation.

PubMed

Furuichi, Yuko; Hamada, Ayaka; Nakazato, Keiko; Kobayashi, Katsuya; Sakamoto, Atsuhiro

2016-12-01

A 69-year-old woman undergoing treatment for hypertension and epilepsy was scheduled to undergo cataract surgery. All preoperative examination results were within normal limits. Despite being tense, she walked to the operating room. Approximately 2 minutes after an intravenous line was established by an anesthesia resident, severe hypoxia and bradycardia developed, and she lost consciousness. Cardiopulmonary resuscitation was initiated immediately, and after 1 minute, she regained consciousness, and her breathing and circulation recovered. After admission to the intensive care unit, emergency coronary angiography was performed. The blood flow in all the coronary arteries was normal. However, a decrease in the apical left ventricular wall motion and an increase in the basal wall motion were observed. Based on these findings, Takotsubo cardiomyopathy was diagnosed. The wall motion gradually improved and the patient was discharged from the hospital on postoperative day 15. The respiratory depression and bradycardia were thought to be due to an inadvertent bolus of remifentanil. We surmised that the patient had received a slight amount of retained medication when the anesthesia resident established the intravenous line, which caused severe respiratory depression. It is important to note that adverse effects such as severe respiratory depression and bradycardia can be caused by even small doses of remifentanil. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Reed, William; Maronpot, Robert R; Henríquez-Roldán, Carlos; Delgado-Chavez, Ricardo; Calderón-Garcidueñas, Ana; Dragustinovis, Irma; Franco-Lira, Maricela; Aragón-Flores, Mariana; Solt, Anna C; Altenburg, Michael; Torres-Jardón, Ricardo; Swenberg, James A

2004-01-01

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

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…

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.

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.

Nebivolol Induced Hyperkalemia: Case Report

PubMed

Altabas, Karmela; Altabas, Velimir; Gulin, Tonko

2016-12-01

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.

Health Effects of Secondhand Smoke

MedlinePlus

... 2014 Surgeon General’s Report 4 Secondhand Smoke Causes Cardiovascular Disease Exposure to secondhand smoke has immediate adverse effects on the cardiovascular system and can cause coronary heart disease and stroke. 2,4,5 Secondhand smoke causes ...

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding.

PubMed

Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Arlier, Sefa; Kayisli, Umit A; Lockwood, Charles J

2016-06-01

Human pregnancy requires robust hemostasis to prevent hemorrhage during extravillous trophoblast (EVT) invasion of the decidualized endometrium, modification of spiral arteries and post-partum processes. However, decidual hemorrhage (abruption) can occur throughout pregnancy from poorly transformed spiral arteries, causing fetal death or spontaneous preterm birth (PTB), or it can promote the aberrant placentation observed in intrauterine growth restriction (IUGR) and pre-eclampsia; all leading causes of perinatal or maternal morbidity and mortality. In non-fertile cycles, the decidua undergoes controlled menstrual bleeding. Abnormal uterine bleeding (AUB) accompanying progestin-only, long-acting, reversible contraception (pLARC) accounts for most discontinuations of these safe and highly effective agents, thereby contributing to unwanted pregnancies and abortion. The aim of this study was to investigate the role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. We conducted a critical review of the literature arising from PubMed searches up to December 2015, regarding in situ and in vitro expression and regulation of several specific proteins involved in uterine hemostasis in decidua and cycling endometrium. In addition, we discussed clinical and molecular mechanisms associated with pLARC-induced AUB and pregnancy complications with abruptions, chorioamnionitis or pre-eclampsia. Progestin-induced decidualization of estradiol-primed human endometrial stromal cells (HESCs) increases in vivo and in vitro expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) while inhibiting plasminogen activators (PAs), matrix metalloproteinases (MMPs), and the vasoconstrictor, endothelin-1 (ET-1). These changes in decidual cell-derived regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone prevent hemorrhage during EVT invasion and vascular remodeling. In non-fertile cycles, progesterone withdrawal reduces TF and PAI-1 while increasing PA, MMPs and ET-1, causing menstrual-associated bleeding, fibrinolysis, ECM degradation and ischemia. First trimester decidual hemorrhage elicits later adverse outcomes including pregnancy loss, pre-eclampsia, abruption, IUGR and PTB. Decidual hemorrhage generates excess thrombin that binds to decidual cell-expressed protease-activated receptors (PARs) to induce chemokines promoting shallow placentation; such bleeding later in pregnancy generates thrombin to down-regulate decidual cell progesterone receptors and up-regulate cytokines and MMPs linked to PTB. Endometria of pLARC users display ischemia-induced excess vasculogenesis and progestin inhibition of spiral artery vascular smooth muscle cell proliferation and migration leading to dilated fragile vessels prone to bleeding. Moreover, aberrant TF-derived thrombin signaling also contributes to the pathogenesis of endometriosis via induction of angiogenesis, inflammation and cell survival. Perivascular decidualized HESCs promote endometrial hemostasis during placentation yet facilitate menstruation through progestational regulation of hemostatic, proteolytic, and vasoactive proteins. Pathological endometrial hemorrhage elicits excess local thrombin generation, which contributes to pLARC associated AUB, endometriosis and adverse pregnancy outcomes through several biochemical mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding

PubMed Central

Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Arlier, Sefa; Kayisli, Umit A.; Lockwood, Charles J.

2016-01-01

BACKGROUND Human pregnancy requires robust hemostasis to prevent hemorrhage during extravillous trophoblast (EVT) invasion of the decidualized endometrium, modification of spiral arteries and post-partum processes. However, decidual hemorrhage (abruption) can occur throughout pregnancy from poorly transformed spiral arteries, causing fetal death or spontaneous preterm birth (PTB), or it can promote the aberrant placentation observed in intrauterine growth restriction (IUGR) and pre-eclampsia; all leading causes of perinatal or maternal morbidity and mortality. In non-fertile cycles, the decidua undergoes controlled menstrual bleeding. Abnormal uterine bleeding (AUB) accompanying progestin-only, long-acting, reversible contraception (pLARC) accounts for most discontinuations of these safe and highly effective agents, thereby contributing to unwanted pregnancies and abortion. The aim of this study was to investigate the role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. METHODS We conducted a critical review of the literature arising from PubMed searches up to December 2015, regarding in situ and in vitro expression and regulation of several specific proteins involved in uterine hemostasis in decidua and cycling endometrium. In addition, we discussed clinical and molecular mechanisms associated with pLARC-induced AUB and pregnancy complications with abruptions, chorioamnionitis or pre-eclampsia. RESULTS Progestin-induced decidualization of estradiol-primed human endometrial stromal cells (HESCs) increases in vivo and in vitro expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) while inhibiting plasminogen activators (PAs), matrix metalloproteinases (MMPs), and the vasoconstrictor, endothelin-1 (ET-1). These changes in decidual cell-derived regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone prevent hemorrhage during EVT invasion and vascular remodeling. In non-fertile cycles, progesterone withdrawal reduces TF and PAI-1 while increasing PA, MMPs and ET-1, causing menstrual-associated bleeding, fibrinolysis, ECM degradation and ischemia. First trimester decidual hemorrhage elicits later adverse outcomes including pregnancy loss, pre-eclampsia, abruption, IUGR and PTB. Decidual hemorrhage generates excess thrombin that binds to decidual cell-expressed protease-activated receptors (PARs) to induce chemokines promoting shallow placentation; such bleeding later in pregnancy generates thrombin to down-regulate decidual cell progesterone receptors and up-regulate cytokines and MMPs linked to PTB. Endometria of pLARC users display ischemia-induced excess vasculogenesis and progestin inhibition of spiral artery vascular smooth muscle cell proliferation and migration leading to dilated fragile vessels prone to bleeding. Moreover, aberrant TF-derived thrombin signaling also contributes to the pathogenesis of endometriosis via induction of angiogenesis, inflammation and cell survival. CONCLUSION Perivascular decidualized HESCs promote endometrial hemostasis during placentation yet facilitate menstruation through progestational regulation of hemostatic, proteolytic, and vasoactive proteins. Pathological endometrial hemorrhage elicits excess local thrombin generation, which contributes to pLARC associated AUB, endometriosis and adverse pregnancy outcomes through several biochemical mechanisms. PMID:26912000

Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004-2006).

PubMed

Kogan, David A; Johnson, Lynelle R; Sturges, Beverly K; Jandrey, Karl E; Pollard, Rachel E

2008-12-01

To evaluate the number and types of underlying disorders detected in dogs with aspiration pneumonia and determine the survival rate among affected dogs. Retrospective case series. Animals-88 dogs with aspiration pneumonia. Medical records were reviewed to identify disease processes that could result in aspiration pneumonia. To assess outcome (ie, survival to discharge from the hospital or nonsurvival), dogs were grouped by the type and number of underlying disease processes. Duration of hospitalization and radiographic severity of disease were evaluated with regard to case outcome. As the cause of aspiration pneumonia, a single underlying disorder was identified in 60 of the 88 dogs; 2 or more diseases were identified in the remaining dogs. Esophageal disease (n = 35), vomiting (34), neurologic disorders (24), laryngeal disease (16), and postanesthetic aspiration (12) were identified most commonly. Overall, 68 dogs survived to discharge from the hospital (survival rate, 77%). Survival rates were comparable among dogs regardless of the underlying cause of aspiration pneumonia. Radiographic severity of disease and duration of hospitalization did not influence survival. Among these study dogs, aspiration pneumonia was associated with a high survival rate. The presence of more than 1 underlying disease associated with aspiration pneumonia did not adversely impact survival rate. Interestingly, radiographic severity of disease and duration of hospitalization were not associated with overall survival rate.

Carvedilol prospective randomized cumulative survival (COPERNICUS) trial: carvedilol in severe heart failure.

PubMed

Fowler, Michael B

2004-05-06

The impact of carvedilol on the survival of patients with severe heart failure was examined in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. The trial recruited 2,289 patients with symptoms at rest or on minimal exertion despite therapy with angiotensin-converting enzyme inhibitors and a left ventricular ejection fraction of < or = 0.25. After an average follow-up period of 10.4 months, mortality was reduced by 34% in the carvedilol group. Carvedilol also reduced the number of days spent in the hospital for any cause by 27% and the number of days spent in the hospital for heart failure by 40%. Patients in the carvedilol group felt better and were less likely to have a serious adverse event. The benefits of carvedilol appeared early and were detected during the up-titration period.

The chemistry side of AOP: implications for toxicity extrapolation

EPA Science Inventory

An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across s...

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

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.

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

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

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

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

Excipients in topical corticosteroid preparations in Canada.

PubMed Central

Searles, G E; DesGroseilliers, J P

1989-01-01

Topical corticosteroids are widely used for the treatment of dermatoses in Canada. The effects of the various nontherapeutic components of these formulations are less well known than those of the active ingredients and may cause adverse reactions. Information on the components is fragmentary and is scattered throughout the literature. We have attempted to consolidate this information into one source. Recent provincial legislation requiring the generic substitution of interchangeable products and the nondisclosure of all ingredients in product labelling hinder the search for an excipient that has caused an adverse reaction. Practitioner participation in the Cutaneous Adverse Reaction Registry of the Canadian Dermatology Association will identify sensitizing excipients and will support efforts by the profession to obtain more effective and safer products. PMID:2766179

Evaluation and treatment of transfusional iron overload in children.

PubMed

Ware, Hannah M; Kwiatkowski, Janet L

2013-12-01

Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. Copyright © 2013 Elsevier Inc. All rights reserved.

[Drug induced diarrhea].

PubMed

Morard, Isabelle; Hadengue, Antoine

2008-09-03

Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

Evaluation and treatment of respiratory alkalosis.

PubMed

Palmer, Biff F

2012-11-01

Respiratory alkalosis is the most frequent acid-base disturbance encountered in clinical practice. This is particularly true in critically ill patients, for whom the degree of hypocapnia directly correlates with adverse outcomes. Although this acid-base disturbance often is considered benign, evidence suggests that the alkalemia of primary hypocapnia can cause clinically significant decreases in tissue oxygen delivery. Mild respiratory alkalosis often serves as a marker of an underlying disease and may not require therapeutic intervention. In contrast, severe respiratory alkalosis should be approached with a sense of urgency and be aggressively corrected. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Sulfite-containing Canadian pharmaceutical products available in 1991.

PubMed Central

Miyata, M; Schuster, B; Schellenberg, R

1992-01-01

OBJECTIVE: To compile an inclusive list of Canadian pharmaceutical products available in 1991 that contained sulfites. DATA SOURCES: Written and oral responses from 94 pharmaceutical companies selected from the 1989 Compendium of Pharmaceuticals and Specialties. RESULTS: A list of sulfite-containing pharmaceutical products was compiled from data supplied by the 90 responding companies. Companies whose products contained no sulfites were separately identified. CONCLUSIONS: Sulfites are present in many pharmaceutical products and are one of many excipients and additives that have been reported to cause severe adverse reactions. The provided list should be a useful aid for health care practitioners when prescribing pharmaceutical products for sulfite-sensitive patients. PMID:1483237

Tobacco in the workplace.

PubMed

Osinubi, Omowunmi Y O; Slade, John

2002-01-01

Tobacco use, the leading cause of preventable death, has numerous adverse impacts in the workplace. It is associated with increased healthcare costs and disability, greater absenteeism, decrements in job performance, and increased risk of injury, and secondhand smoke is a major pollution problem. Tobacco dependence responds to treatment, and employers have several opportunities to offer treatment to employees and their families. Smoke-free environments can help smokers cut back or quit. Combining sound workplace policies and treatment with community involvement in tobacco control provides synergies to reduce tobacco use in the community as well as in the workforce. These activities benefit workers and their families, employers, and society at large.

Dioxin uptake by Indian plant species.

PubMed

Pandey, J S; Kumar, R; Wate, S R

2008-08-01

Dioxins like various gaseous pollutants and aerosols can be scavenged by appropriate vegetative greenbelts. Based on their stomatal properties and the models for contaminant uptake, uptake of dioxin (2,3,7,8-TCDD) by three important Indian plant species, viz. Eugenia jambolana (Jamun), Azadirachta indica (Neem) and Ficus religiosa (Peepal), has been estimated. 2,3,7,8-TCDD is a contaminant with severe harmful ecological ramifications. Computations show that Ficus religiosa has highest uptake capacity. The present exercise has its utility in designing appropriate green-belts for mitigating adverse environmental and human health impacts due to dioxins. This can be an effective management option for mitigating the damages caused by dioxins.

Physical and mental health functioning after all-cause and diagnosis-specific sickness absence: a register-linkage follow-up study among ageing employees.

PubMed

Mänty, Minna; Lallukka, Tea; Lahti, Jouni; Pietiläinen, Olli; Laaksonen, Mikko; Lahelma, Eero; Rahkonen, Ossi

2017-01-25

Sickness absence has been shown to be a risk marker for severe future health outcomes, such as disability retirement and premature death. However, it is poorly understood how all-cause and diagnosis-specific sickness absence is reflected in subsequent physical and mental health functioning over time. The aim of this study was to examine the association of all-cause and diagnosis-specific sickness absence with subsequent changes in physical and mental health functioning among ageing municipal employees. Prospective survey and register data from the Finnish Helsinki Health Study and the Social Insurance Institution of Finland were used. Register based records for medically certified all-cause and diagnostic-specific sickness absence spells (>14 consecutive calendar days) in 2004-2007 were examined in relation to subsequent physical and mental health functioning measured by Short-Form 36 questionnaire in 2007 and 2012. In total, 3079 respondents who were continuously employed over the sickness absence follow-up were included in the analyses. Repeated-measures analysis was used to examine the associations. During the 3-year follow-up, 30% of the participants had at least one spell of medically certified sickness absence. All-cause sickness absence was associated with lower subsequent physical and mental health functioning in a stepwise manner: the more absence days, the poorer the subsequent physical and mental health functioning. These differences remained but narrowed slightly during the follow-up. Furthermore, the adverse association for physical health functioning was strongest among those with sickness absence due to diseases of musculoskeletal or respiratory systems, and on mental functioning among those with sickness absence due to mental disorders. Sickness absence showed a persistent adverse stepwise association with subsequent physical and mental health functioning. Evidence on health-related outcomes after long-term sickness absence may provide useful information for targeted interventions to promote health and workability.

[Adverse effects of oxcarbazepine].

PubMed

Fang, Shu; Gong, Zhi-Cheng

2015-04-01

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

Nuclear Accident Crisis and Liver Disease: A Summary on Evidences

PubMed Central

Wiwanitkit, Viroj

2013-01-01

The present global concern is on the adverse effect due to exposure to nuclides expelled from the disrupted nuclear power plant accident in Japan. The exposure can induce several adverse effects. In this specific brief review, the author summarizes the evidences on the effect on liver. Discussion is focused on several liver diseases. PMID:25125994

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman

PubMed Central

Tan, Jackie; Pretorius, Casper Francois; Flanagan, Paul Vincent; Pais, Antonio

2012-01-01

Rosuvastatin (Crestor, AstraZeneca) is a commonly used drug for managing hypercholesterolaemia. It is a very safe medication with mostly acceptable side effects. Rare but serious side effects are not well known. A 64-year-old woman presented with bloody diarrhoea after starting rosuvastatin for hypercholesterolaemia. Stool microscopy and culture ruled out infective causes. Abdominal CT scan revealed normal calibre celiac axis and superior mesenteric artery. Colonoscopic biopsy revealed ischaemic colitis as the final histological diagnosis. The patient is in complete remission after ceasing the medication. Rosuvastatin causing ischaemic colitis should be considered a rare but serious adverse drug reaction. PMID:22744258

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...

High doses alprazolam induced amenorrhoea and galactorrhoea.

PubMed

Petrić, Daniela; Peitl, Marija Vučić; Peitl, Vjekoslav

2011-03-01

Alprazolam belongs in the group of anxiolytics, medicaments used for reducing anxiety. As most other drugs, it can cause various adverse events, including hormonal disturbances and imbalance. Prolactin elevation is one such hormonal adverse event that can lead to galactorrhoea, or abnormal milk discharge from the breast and amenorrhoea. In this case report we will present the case of a female patient that developed galactorrhoea while treated with alprazolam, after all physical factors that can also cause these symptoms were excluded.

Investigation into the effects of VHF and UHF band radiation on Hewlett-Packard (HP) Cesium Beam Frequency Standards

NASA Technical Reports Server (NTRS)

Dickens, Andrew

1995-01-01

This paper documents an investigation into reports which have indicated that exposure to VHF and UHF band radiation has adverse effects on the frequency stability of HP cesium beam frequency standards. Tests carried out on the basis of these reports show that sources of VHF and UHF radiation such as two-way hand held police communications devices do cause reproducible adverse effects. This investigation examines reproducible effects and explores possible causes.

Exposure to Nickel, Chromium, or Cadmium Causes Distinct Changes in the Gene Expression Patterns of a Rat Liver Derived Cell Line

DTIC Science & Technology

2011-11-16

nickel, cadmium, and chromium are toxic industrial chemicals with an exposure. While these substances are known to produce adverse health effects leading...in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects...that particular bin. A chi-squared test was used to test bin enrichment ( p ≤0.05). Probe sets that did not contain any biological process annotation were

[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.

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.

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.

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

EPA Science Inventory

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients

PubMed Central

Jiao, Lijing; Dong, Changsheng; Liu, Jiaxiang; Chen, Zhiwei; Zhang, Lei; Xu, Jianfang; Shen, Xiaoyong; Che, Jiaming; Yang, Yi; Huang, Hai; Li, Hegen; Sun, Jianli; Jiang, Yi; Mao, Zhujun; Chen, Peiqi; Gong, Yabin; Jin, Xiaolin; Xu, Ling

2017-01-01

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens. PMID:28436479

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.

Social Determinants of Health, Disaster Vulnerability, Severe and Morbid Obesity in Adults: Triple Jeopardy?

PubMed Central

2017-01-01

Severe and morbid obesity are associated with highly elevated risks of adverse health outcomes and the prevalence of severe obesity is increasing globally. To date, disaster literature has not considered severe and morbid obesity as a specific vulnerability, despite reports of people being left behind during disasters because of their body size, shape or weight. The complex causes of obesity are associated with the social determinants of health and one’s potential vulnerability to disasters. The absence of appropriate considerations may lead to people being exposed to disproportionate and potentially avoidable risk. The intersection of the social determinants of health, disaster vulnerability, severe and morbid obesity is explored. Previously identified vulnerable groups are also represented in severe and morbid obesity data. This poses the prospect for ‘triple jeopardy’ compounding the social determinants of health, disaster vulnerability and considerations with and for people with morbid obesity. When working to reduce disaster risk for vulnerable groups, the author proposes specific consideration is required to ensure ‘all-of-society engagement and partnership’ in an inclusive, accessible and non-discriminatory manner, to ensure no one is left behind.

Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury.

PubMed

Schiffl, Helmut; Lang, Susanne M

2013-02-01

Hypophosphatemia during renal replacement therapy (RRT) is common in critically ill patients with acute kidney injury (AKI). The clinical consequences of RRT-induced phosphate depletion are not well defined in this patient population, and there is no evidence that intravenous sodium phosphate supplementation (PS) prevents the clinical sequelae of acute hypophosphatemia. The purpose of this retrospective analysis of the Acute Renal Support Registry of the University of Munich was to examine the association between severe hypophosphatemia and severity of and recovery from AKI. 289 ICU patients with AKI on intermittent hemodialysis (IHD) were included in the study. One hundred and forty-nine patients received PS during IHD. Outcomes were short-term (at discharge) and long-term (at 1 year) recovery of renal function and mortality. The two patient groups did not differ in demographics, clinical features, renal characteristics, and frequency of hypophosphatemia at initiation of IHD. Without PS, the frequency of hypophosphatemia increased from 20 to 35%. Severe hypophosphatemia was found in 50% of these patients. By comparison, PS was not associated with an increased frequency of hypophosphatemia. Compared with patients with acute phosphate depletion, patients receiving PS developed less oliguria during IHD, had shorter duration of AKI, higher incidence of complete renal recovery at discharge, and a lower risk of de novo chronic kidney disease. Hypophosphatemia was associated with higher all-cause in-hospital mortality and higher risk of long-term mortality. This multicenter study indicates for the first time that hypophosphatemia during IHD adversely affects short- and long-term outcome of critically-ill patients with AKI. The clinical consequences of the acute hypophosphatemic syndrome may be prevented by PS.

Vedolizumab: an α4β7 integrin antagonist for ulcerative colitis and Crohn’s disease

PubMed Central

Cherry, Lauren N.; Yunker, Nancy S.; Lambert, Erika R.; Vaughan, DaleMarie

2015-01-01

Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted. PMID:26336591

Developmental Patterns of Adverse Childhood Experiences and Current Symptoms and Impairment in Youth Referred For Trauma-Specific Services.

PubMed

Grasso, Damion J; Dierkhising, Carly B; Branson, Christopher E; Ford, Julian D; Lee, Robert

2016-07-01

By the time children reach adolescence, most have experienced at least one type of severe adversity and many have been exposed to multiple types. However, whether patterns of adverse childhood experiences are consistent or change across developmental epochs in childhood is not known. Retrospective reports of adverse potentially traumatic childhood experiences in 3 distinct developmental epochs (early childhood, 0- to 5-years-old; middle childhood, 6- to 12-years-old; and adolescence, 13- to 18-years-old) were obtained from adolescents (N = 3485) referred to providers in the National Child Traumatic Stress Network (NCTSN) for trauma-focused assessment and treatment. Results from latent class analysis (LCA) revealed increasingly complex patterns of adverse/traumatic experiences in middle childhood and adolescence compared to early childhood. Depending upon the specific developmental epoch assessed, different patterns of adverse/traumatic experiences were associated with gender and with adolescent psychopathology (e.g., internalizing/externalizing behavior problems), and juvenile justice involvement. A multiply exposed subgroup that had severe problems in adolescence was evident in each of the 3 epochs, but their specific types of adverse/traumatic experiences differed depending upon the developmental epoch. Implications for research and clinical practice are identified.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

PubMed Central

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-01-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. PMID:27044768

Trace elements in coal. Environmental and health significance

USGS Publications Warehouse

Finkelman, R.B.

1999-01-01

Trace elements can have profound adverse effects on the health of people burning coal in homes or living near coal deposits, coal mines, and coal- burning power plants. Trace elements such as arsenic emitted from coal- burning power plants in Europe and Asia have been shown to cause severe health problems. Perhaps the most widespread health problems are caused by domestic coal combustion in developing countries where millions of people suffer from fluorosis and thousands from arsenism. Better knowledge of coal quality characteristics may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals in coal may help to predict the behavior of the potentially toxic trace metals during coal cleaning, combustion, weathering, and leaching.

Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting: a case report.

PubMed

Bansal, Rinkesh Kumar; Tyagi, Pankaj; Sharma, Praveen; Singla, Vikas; Arora, Veronica; Bansal, Naresh; Kumar, Ashish; Arora, Anil

2014-02-26

Vitamin D is increasingly recognized to have several beneficial effects. Vitamin D deficiency is widely prevalent. Physicians often treat patients with high doses of vitamin D for various ailments without any monitoring for adverse effects and the prescribed doses often far exceed requirements resulting in toxicity. We present here a classic case of iatrogenic hypervitaminosis D, which presented with persistent vomiting and acute renal failure. Here we present a case of a 45-year-old Asian Indian woman who presented to us with persistent vomiting the cause of which was iatrogenic hypervitaminosis D. She was treated with intravenous fluid, diuretics and calcitonin and had clinical improvement. We suggest that in any patient presenting with persistent vomiting and hypercalcemia, particularly in the presence of normal parathyroid hormone, a diagnosis of overdose of vitamin D should be suspected. Its treatment not only alleviates symptoms but also prevents ongoing acute kidney injury.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

PubMed

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-03-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Fluoride concentration level in rural area in Poldasht city and daily fluoride intake based on drinking water consumption with temperature.

PubMed

Mohammadi, Ali Akbar; Yousefi, Mahmood; Mahvi, Amir Hossein

2017-08-01

Long-term exposure to high level of fluoride can caused several adverse effects on human health including dental and skeletal fluorosis. We investigated all the drinking water source located in rural areas of Poldasht city, west Azerbaijan Province, North West Iran between 2014 and 2015. Fluoride concentration of water samples was measured by SPADNS method. We found that in the villages of Poldasht the average of fluoride concentration in drinking water sources (well, and the river) was in the range mg/l 0.28-10.23. The average daily received per 2 l of drinking water is in the range mg/l 0.7-16.6 per day per person. Drinking water demands cause fluorosis in the villages around the area residents and based on the findings of this study writers are announced suggestions below in order to take care of the health of area residents.

Altered immunological response in mice subjected to stress and exposed to fungal spores

NASA Technical Reports Server (NTRS)

Kurup, Viswanath P.; Choi, Hongyung; Kumar, Anoopa; Murali, Pazhayannur S.; Mishra, S. K.; Pierson, Duane L.

1992-01-01

Space flight and related factors such as stress appear to have an adverse effect on astronauts' immune systems. The presence of potentially pathogenic microbes including several genera of fungi reported from spacecraft environment may be a cause of concern in such situations. In order to study the role of such organisms in causing opportunistic or allergic diseases in crewmembers, we have tried to develop an animal model. BALB/c mice were suspended upside down for varying periods of time to induce stress, and their lymphocyte functions were evaluated. These studies indicate that the stress resulted in lowered mitogen induced lymphocyte stimulation as represented by 3H-thymidine uptake. We have also studied the ability of these animals to respond to Aspergillus fumigatus spores. The results of the study clearly demonstrate a definite down-regulation in T-cell proliferation and a higher incidence of infection with A. fumigatus.

Penalizing hospitals for chronic obstructive pulmonary disease readmissions.

PubMed

Feemster, Laura C; Au, David H

2014-03-15

In October 2014, the U.S. Centers for Medicare and Medicaid Services (CMS) will expand its Hospital Readmission Reduction Program (HRRP) to include chronic obstructive pulmonary disease (COPD). Under the new policy, hospitals with high risk-adjusted, 30-day all-cause unplanned readmission rates after an index hospitalization for a COPD exacerbation will be penalized with reduced reimbursement for the treatment of Medicare beneficiaries. In this perspective, we review the history of the HRRP, including the recent addition of COPD to the policy. We critically assess the use of 30-day all-cause COPD readmissions as an accountability measure, discussing potential benefits and then highlighting the substantial drawbacks and potential unintended consequences of the measure that could adversely affect providers, hospitals, and patients with COPD. We conclude by emphasizing the need to place the 30-day COPD readmission measure in the context of a reconceived model for postdischarge quality and review several frameworks that could help guide this process.

Bleeding risks of herbal, homeopathic, and dietary supplements: a hidden nightmare for plastic surgeons?

PubMed

Wong, Wendy W; Gabriel, Allen; Maxwell, G Patrick; Gupta, Subhas C

2012-03-01

The utilization of complementary and alternative medicine has increased tremendously in the last two decades. Herbal products, homeopathic medicines, and dietary supplements are extremely popular and are available without a prescription (which likely contributes to their popularity). Despite their "natural" characteristics, these remedies have the potential to cause bleeding in patients who undergo surgery. The high use of these supplements among cosmetic surgery patients, coupled with increasing reports of hematomas associated with herbal and homeopathic medicines, prompted the authors to conduct a comprehensive review focused on bleeding risks of such products in an effort to raise awareness among plastic surgeons. This review focuses on 19 herbs, three herbal formulas, two herbal teas, and several other supplements that can cause bleeding perioperatively and postoperatively. In addition to being aware of such adverse effects, plastic surgeons must adequately screen all patients and educate them on the possible dangers associated with these treatments.

Depression as an independent prognostic factor for all-cause mortality after a hospital admission for worsening heart failure.

PubMed

Sokoreli, I; de Vries, J J G; Riistama, J M; Pauws, S C; Steyerberg, E W; Tesanovic, A; Geleijnse, G; Goode, K M; Crundall-Goode, A; Kazmi, S; Cleland, J G; Clark, A L

2016-10-01

Depression is associated with increased mortality amongst patients with chronic heart failure (HF). Whether depression is an independent predictor of outcome in patients admitted for worsening of HF is unclear. OPERA-HF is an observational study enrolling patients hospitalized with worsening HF. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D) questionnaire. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). Kaplan-Meier and Cox regression analyses were used to estimate the association between depression and all-cause mortality. Of 242 patients who completed the HADS-D questionnaire, 153, 54 and 35 patients had no (score 0-7), mild (score 8-10) or moderate-to-severe (score 11-21) depression, respectively. During follow-up, 35 patients died, with a median time follow-up of 360days amongst survivors (interquartile range, IQR 217-574days). In univariable analysis, moderate-to-severe depression was associated with an increased risk of death (HR: 4.9; 95% CI: 2.3 to 10.2; P<0.001) compared to no depression. Moderate-to-severe depression also predicted all-cause mortality after controlling for age, CCI score, NYHA class IV, NT-proBNP and treatment with mineralocorticoid receptor antagonist, beta-blocker and diuretics (HR: 3.0; 95% CI: 1.3 to 7.0; P<0.05). Depression is strongly associated with an adverse outcome in the year following discharge after an admission to hospital for worsening HF. The association is only partly explained by the severity of HF or comorbidity. Further research is required to demonstrate whether recognition and treatment of depression improves patient outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Industrial wind turbines and adverse health effects.

PubMed

Jeffery, Roy D; Krogh, Carmen M E; Horner, Brett

2014-01-01

Some people living in the environs of industrial wind turbines (IWTs) report experiencing adverse health and socioeconomic effects. This review considers the hypothesis that annoyance from audible IWTs is the cause of these adverse health effects. We searched PubMed and Google Scholar for articles published since 2000 that included the terms "wind turbine health," "wind turbine infrasound," "wind turbine annoyance," "noise annoyance" or "low frequency noise" in the title or abstract. Industrial wind turbines produce sound that is perceived to be more annoying than other sources of sound. Reported effects from exposure to IWTs are consistent with well-known stress effects from persistent unwanted sound. If placed too close to residents, IWTs can negatively affect the physical, mental and social well-being of people. There is sufficient evidence to support the conclusion that noise from audible IWTs is a potential cause of health effects. Inaudible low-frequency noise and infrasound from IWTs cannot be ruled out as plausible causes of health effects.

Serious adverse events associated with yellow fever vaccine.

PubMed

de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

2015-01-01

Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Starobova, Hana; Vetter, Irina

2017-01-01

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280

Comparison of resorbable poly-L-lactic acid-polyglycolic acid and internal Palmaz stents for the surgical correction of severe tracheomalacia.

PubMed

Sewall, Gregory K; Warner, Thomas; Connor, Nadine P; Hartig, Gregory K

2003-06-01

Tracheomalacia (TM) is associated with expiratory airway collapse and potentially fatal respiratory distress. Internal and external tracheal stents and, recently, resorbable biopolymers have been used to treat this condition. In this study, the efficacy and biocompatibility of internal Palmaz stents and external poly-L-lactic acid-polyglycolic acid (PLPG) stents were compared in a model of severe TM induced in piglets. The tracheas were repaired with one of two stenting methods, and the animals survived for up to 16 weeks. Weight gain, adverse respiratory signs and symptoms, tracheal or lung histopathologic changes, and internal and external tracheal diameters were measured. The animals in the PLPG group uniformly were free of respiratory distress and tracheal stenosis or inflammation, whereas all animals in the Palmaz group developed respiratory distress as a result of pneumonia or tracheal stenosis caused by intraluminal granulation tissue. In conclusion, superior efficacy of external, resorbable PLPG stents was found relative to internal Palmaz stents for the surgical repair of severe TM.

Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography.

PubMed

O'Driscoll, Jamie M; Gargallo-Fernandez, Paula; Araco, Marco; Perez-Lopez, Manuel; Sharma, Rajan

2017-11-01

A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. 6745 patients (mean age 64.9 ± 12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1 ± 1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p < 0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p < 0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17-3.57 and HR 3.62; 95% CI 2.89-4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results.

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database.

PubMed

Naganuma, Misa; Motooka, Yumi; Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Fukuda, Akiho; Nakao, Satoshi; Shimada, Kazuyo; Hirade, Koseki; Mori, Takayuki; Yoshimura, Tomoaki; Kato, Takeshi; Nakamura, Mitsuhiro

2018-01-01

Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5-3.0), 0.6 (0.5-0.7), 0.8 (0.7-1.0), and 1.3 (0.8-2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower-upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0-8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were <1. In the association rule mining, the score of lift for patients who were treated with cisplatin and co-administered furosemide, loxoprofen, or pemetrexed was high. Similarly, the scores for patients with hypertension or diabetes mellitus were high. Our findings suggest a potential risk of renal impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient's background prior to treatment.

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

PubMed

Bobes, Julio; Rejas, J; Garcia-Garcia, M; Rico-Villademoros, F; García-Portilla, M P; Madrigal, M; Hernández, G

2002-09-01

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ 2 ) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ 2 : p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ 2 : p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ 2 : p < 0.05). Olanzapine, quetiapine and risperidone also showed a lower risk of EPS than haloperidol when adjusting by dose. Our results suggest that the atypical antipsychotics studied are less likely to induce extrapyramidal adverse reactions compared with haloperidol in stabilised patients, although these reactions are still common.

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

PubMed

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

2018-04-01

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

ACHP | Section 106 Regulations Flow Chart

Science.gov Websites

undertaking/no potential to cause effects Undertaking is type that might affect historic properties Identify No historic properties affected Historic properties are affected Assess Adverse Effects Apply affected Resolve Adverse Effects Continue consultation Memorandum of Agreement FAILURE TO AGREE COUNCIL

Root cause analysis of critical events in neurosurgery, New South Wales.

PubMed

Perotti, Vanessa; Sheridan, Mark M P

2015-09-01

Adverse events reportedly occur in 5% to 10% of health care episodes. Not all adverse events are the result of error; they may arise from systemic faults in the delivery of health care. Catastrophic events are not only physically devastating to patients, but they also attract medical liability and increase health care costs. Root cause analysis (RCA) has become a key tool for health care services to understand those adverse events. This study is a review of all the RCA case reports involving neurosurgical patients in New South Wales between 2008 and 2013. The case reports and data were obtained from the Clinical Excellence Commission database. The data was then categorized by the root causes identified and the recommendations suggested by the RCA committees. Thirty-two case reports were identified in the RCA database. Breaches in policy account for the majority of root causes identified, for example, delays in transfer of patients or wrong-site surgery, which always involved poor adherence to correct patient and site identification procedures. The RCA committees' recommendations included education for staff, and improvements in rostering and procedural guidelines. RCAs have improved the patient safety profile; however, the RCA committees have no power to enforce any recommendation or ensure compliance. A single RCA may provide little learning beyond the unit and staff involved. However, through aggregation of RCA data and dissemination strategies, health care workers can learn from adverse events and prevent future events from occurring. © 2015 Royal Australasian College of Surgeons.

Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study.

PubMed

Pfitscher, L C; Cecatti, J G; Pacagnella, R C; Haddad, S M; Parpinelli, M A; Souza, J P; Quintana, S M; Surita, F G; Sousa, M H; Costa, M L

2016-05-21

The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

PubMed

Kovesdy, Csaba P; Matsushita, Kunihiro; Sang, Yingying; Brunskill, Nigel J; Carrero, Juan J; Chodick, Gabriel; Hasegawa, Takeshi; Heerspink, Hiddo L; Hirayama, Atsushi; Landman, Gijs W D; Levin, Adeera; Nitsch, Dorothea; Wheeler, David C; Coresh, Josef; Hallan, Stein I; Shalev, Varda; Grams, Morgan E

2018-05-01

Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

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

PubMed

Silas, Reshma; Tibballs, James

2010-12-01

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

Propylene Glycol-Related Delirium After Esmolol Infusion.

PubMed

Kapitein, Berber S; Biesmans, Renee S C G; van der Sijs, Heleen S I; de Wildt, Saskia S N

2014-07-01

Excipients used in oral or intravenous preparations may cause serious adverse events. We present the case of a 15-year-old boy with hypertrophic cardiomyopathy. In the pediatric intensive care unit, he received high doses of continuous intravenous esmolol (range = 20-400 µg/kg/min) for cardiac rhythm control. After a few days he developed a delirium not responding to high doses of antipsychotics or discontinuation of benzodiazepines. We eventually realized that the IV esmolol formulation contained high doses of propylene glycol and ethanol, which may accumulate after prolonged infusion and cause intoxication. Intoxication with propylene glycolcan cause neuropsychiatric symptoms. The boy's propylene glycol plasma concentration was approximately 4 g/L, whereas clinical symptoms arise at concentrations above 1 to 1.44 g/L. Application of the Naranjo adverse drug reaction probability scale suggested a probable relationship (score 6) between the propylene glycol infusion and the delirium. After discontinuation of esmolol, the delirium disappeared spontaneously. This is the first case describing excipient toxicity of esmolol, with an objective causality assessment revealing a probable relationship for the adverse event-namely, delirium-and esmolol. Although excipient toxicity is a well-known adverse drug reaction, this case stresses the importance for easily available information for and education of physicians. © The Author(s) 2014.

Improving emergency response to motor vehicle crashes : the role of multi-media information.

DOT National Transportation Integrated Search

2013-10-01

The motivation for this study is to reduce the adverse impacts of trauma caused by motor vehicle crash (MVC), including rural regions, where crashes account for a high percentage of trauma injury and death. One key aspect of reducing adverse effects ...

75 FR 8353 - Waiver of Filing Deadline Due to Adverse Weather Conditions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... FEDERAL COMMUNICATIONS COMMISSION Waiver of Filing Deadline Due to Adverse Weather Conditions... weather conditions, the Federal Communications Commission closed early on Friday, February 5, and closed... closings and disruptions caused by the weather in the Washington, DC area, all paper and electronic filings...

Elevated aminopeptidase N affects sperm motility and early embryo development

PubMed Central

Ryu, Do-Yeal; Kwon, Woo-Sung

2017-01-01

Aminopeptidase N (APN) is a naturally occurring ectopeptidase present in mammalian semen. Previous studies have demonstrated that APN adversely affects male fertility through the alteration of sperm motility. This enzyme constitutes 0.5 to 1% of the seminal plasma proteins, which can be transferred from the prostasomes to sperms by a fusion process. In the present study, we investigated the molecular mechanism of action of APN and its role in regulating sperm functions and male fertility. In this in vitro study, epididymal mouse spermatozoa were incubated in a capacitating media (pH 7) containing 20 ng/mL of recombinant mouse APN for 90 min. Our results demonstrated that the supplementation of recombinant APN in sperm culture medium significantly increased APN activity, and subsequently altered motility, hyperactivated motility, rapid and medium swimming speeds, viability, and the acrosome reaction of mouse spermatozoa. These effects were potentially caused by increased toxicity in the spermatozoa. Further, altered APN activity in sperm culture medium affected early embryonic development. Interestingly, the effect of elevated APN activity in sperm culture medium was independent of protein tyrosine phosphorylation and protein kinase A activity. On the basis of these results, we concluded that APN plays a significant role in the regulation of several sperm functions and early embryonic development. In addition, increased APN activity could potentially lead to several adverse consequences related to male fertility. PMID:28859152

Phenylephrine eye drops in pediatric patients undergoing ophthalmic surgery: incidence, presentation, and management of complications during general anesthesia.

PubMed

Sbaraglia, Fabio; Mores, Nadia; Garra, Rossella; Giuratrabocchetta, Giuseppe; Lepore, Domenico; Molle, Fernando; Savino, Gustavo; Piastra, Marco; Pulitano', Silvia; Sammartino, Maria

2014-04-01

Phenylephrine eye drops are widely used as mydriatic agent to reach the posterior segment of the eye. In literature, many reports suggest a systemic absorption of this agent as a source of severe adverse drug reactions. Hence, we reviewed our experience with topical phenylephrine in ophthalmic surgery. In May 2006, following US guidelines publication, a standard operating procedure was issued in our operating rooms to standardize the use of phenylephrine eye drops in our practice. Two years later, after the occurrence of a cluster of serious adverse drug reactions in infants undergoing surgery, a review of phenylephrine safety and systemic complications incidence was performed. We observed 451 pediatric patients, and 187 met the inclusions criteria: Among them, 4 experienced hemodynamic complications due to phenylephrine eye drops. The incidence of major complications was 2.1%. Two different patterns of side effects occurred. The first one was a cardiovascular derangement with severe hypertension and heart rate alterations; the other one involved exclusively pulmonary circuit causing early edema. These clinical manifestations, their duration, and treatment responses are all explainable by alfa1-adrenergic action of phenylephrine. This hypothetic pathogenesis has been confirmed also by the usefulness of direct vasodilators (anesthetic agents) and by the negative outcome occurred in the past with the use of beta-blockers. © 2013 John Wiley & Sons Ltd.

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

PubMed Central

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

2016-01-01

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

Risks associated with melamine and related triazine contamination of food

PubMed Central

Baynes, RE; Riviere, JE

2009-01-01

Recent adulteration of milk products with melamine (ME) in several countries caused adverse health effects and even deaths in infants. Earlier, in 2007, contamination of pet food with ME and its related contaminants was associated with many clinical cases of canine and feline nephrotoxicity, and in some cases mortality. ME is a triazine compound that is often detected with other triazine analogs such as cyanuric acid. As is the custom in some livestock operations, the contaminated pet food was mixed with feed intended for the swine and poultry industry. This practice has raised several questions as to whether ME and its related triazines would adversely affect the health of these food animals, and whether meat products derived from swine and poultry could contain high-enough levels of these contaminants to warrant public health concern. Data for this review article were obtained from recent research efforts in our laboratory, peer-reviewed publications cited in PubMed, and information available at USDA, US FDA, and WHO websites. The primary issues discussed are related to (1) the chemistry and interactions between ME and its triazine analogs; (2) reported animal and human exposures with possible pathways through which ME can enter the human food chain; (3) mammalian toxicology; (4) comparative pharmacokinetics (PK) and modeling strategies used to predict residue levels; and (5) emerging issues and management strategies. PMID:22460395

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk

PubMed Central

Schaefer, Benedikt; Würtinger, Philipp; Finkenstedt, Armin; Braithwaite, Vickie; Viveiros, André; Effenberger, Maria; Sulzbacher, Irene; Moschen, Alexander; Griesmacher, Andrea; Tilg, Herbert; Vogel, Wolfgang; Zoller, Heinz

2016-01-01

Background Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM. Aim To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort. Methods Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included. Results The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM—OR = 20.8; 95% CI, 2.6–166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation. Conclusion Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM. PMID:27907058

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk.

PubMed

Schaefer, Benedikt; Würtinger, Philipp; Finkenstedt, Armin; Braithwaite, Vickie; Viveiros, André; Effenberger, Maria; Sulzbacher, Irene; Moschen, Alexander; Griesmacher, Andrea; Tilg, Herbert; Vogel, Wolfgang; Zoller, Heinz

2016-01-01

Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM. To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort. Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included. The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation. Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

A comparison of clinical features of coronary artery spasm with and without thyrotoxicosis.

PubMed

Lee, Soo Youn; Yu, Cheol Woong; Choi, Young Jin; Choi, Rak Kyeong; Park, Jin Sik; Lee, Hyun Jong; Kim, Je Sang; Jang, Ho Jun; Jang, Duck Hyun; Chae, Myung Joon; Shim, Won Heum; Ro, Young Moo

2014-03-01

Several reports have suggested that thyrotoxicosis may induce severe coronary artery spasm (CAS). However, there are few data regarding the differences in clinical characteristics of CAS with and without thyrotoxicosis. The aim of our study is to compare the clinical features of CAS with and without thyrotoxicosis. We evaluated 430 consecutive patients with CAS [patients with thyrotoxicosis (N=32, group I) and those without (N=398, group II)] at a single institute between January 2001 and June 2011. We compared clinical presentations, angiographic findings, and adverse outcomes (a composite outcome of cardiac death, myocardial infarction, or rehospitalization due to cardiac cause) of both groups. There was higher incidence of acute myocardial infarction at initial presentation in group I (15.6 vs. 5.8%, P=0.04). CAS with thyrotoxicosis was more diffuse (59.4 vs. 39.3%, P=0.03), more medically intractable (9.4 vs. 0%, P=0.001), and more frequently involved the left main vessel (25.0 vs.0.8%, P=0.001) than CAS without thyrotoxicosis. During the follow-up period (median 43 months), there were no significant differences between the two groups in terms of the risk of adverse outcomes (hazard ratio for CAS with thyrotoxicosis, 1.029; 95% confidence interval, 0.347-3.054). Clinical and angiographic presentations of CAS with thyrotoxicosis were more severe than CAS without thyrotoxicosis, but clinical outcomes were similar in both groups. Optimal vasodilator therapy is essential for the management of CAS with thyrotoxicosis. Thyroid function test should be mandatory for all patients with CAS.

Methanol exposure interferes with morphological cell movements in the Drosophila embryo and causes increased apoptosis in the CNS.

PubMed

Mellerick, Dervla M; Liu, Heather

2004-09-05

Despite the significant contributions of tissue culture and bacterial models to toxicology, whole animal models for developmental neurotoxins are limited in availability and ease of experimentation. Because Drosophila is a well understood model for embryonic development that is highly accessible, we asked whether it could be used to study methanol developmental neurotoxicity. In the presence of 4% methanol, approximately 35% of embryos die and methanol exposure leads to severe CNS defects in about half those embryos, where the longitudinal connectives are dorsally displaced and commissure formation is severely reduced. In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure. Although we did not find any evidence to suggest that methanol exposure affects the capacity of neuroblasts to divide or induces inappropriate apoptosis in these cells, in the CNS of germ band retracted embryos, the number of apoptotic nuclei is significantly increased in methanol-exposed embryos in comparison to controls, particularly in and adjacent to the ventral midline. Apoptosis contributes significantly to methanol neurotoxicity because embryos lacking the cell death genes grim, hid, and reaper have milder CNS defects resulting from methanol exposure than wild-type embryos. Our data suggest that when neurons and glia are severely adversely affected by methanol exposure, the damaged cells are cleared by apoptosis, leading to embryonic death. Thus, the Drosophila embryo may prove useful in identifying and unraveling mechanistic aspects of developmental neurotoxicity, specifically in relation to methanol toxicity.

OAE: The Ontology of Adverse Events.

PubMed

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

2014-01-01

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

Application of nanosheets as an anti-adhesion barrier in partial hepatectomy.

PubMed

Niwa, Daisuke; Koide, Masatsugu; Fujie, Toshinori; Goda, Nobuhito; Takeoka, Shinji

2013-10-01

Postoperative adhesion often causes serious adverse effects such as bowl obstruction, chronic abdominal pain, pelvic pain, and infertility. We previously reported that a poly-L-lactic acid (PLLA) nanosheet can efficiently seal a surgical incision without scarring. In this report, we examined whether the PLLA nanosheet can form an effective anti-adhesion barrier in partial hepatectomy accompanied by severe hemorrhaging in rats. To evaluate the anti-adhesive property of the nanosheet, the liver wound surface was covered with TachoComb(®) , a well-known hemostat material used in clinical procedures, and then with the PLLA nanosheet. Dressing the wound surface with TachoComb(®) alone caused severe adhesion with omentum and/or residual parts of the liver. By contrast, combinational usage of TachoComb(®) and the PLLA nanosheet significantly reduced such adhesion, presumably by inhibiting the permeation of oozing blood cells and the infiltration of fibroblastic cells. Moreover, the nanosheet displayed low permeability against serum proteins as well as cells in vitro, supporting the notion that the PLLA nanosheet has anti-adhesive properties in vivo. These results strongly suggested that the PLLA nanosheet is a promising material for reducing unwanted postoperative adhesion. Copyright © 2013 Wiley Periodicals, Inc.

Adverse effects of cannabis.

PubMed

2011-01-01

Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.

Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.

PubMed

Yogasundaram, Haran; Hung, Whitney; Paterson, Ian D; Sergi, Consolato; Oudit, Gavin Y

2018-06-01

Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Sourdough-Based Biotechnologies for the Production of Gluten-Free Foods

PubMed Central

Nionelli, Luana; Rizzello, Carlo Giuseppe

2016-01-01

Sourdough fermentation, a traditional biotechnology for making leavened baked goods, was almost completely replaced by the use of baker’s yeast and chemical leavening agents in the last century. Recently, it has been rediscovered by the scientific community, consumers, and producers, thanks to several effects on organoleptic, technological, nutritional, and functional features of cereal-based products. Acidification, proteolysis, and activation of endogenous enzymes cause several changes during sourdough fermentation, carried out by lactic acid bacteria and yeasts, which positively affect the overall quality of the baked goods. In particular, the hydrolysis of native proteins of the cereal flours may improve the functional features of baked goods. The wheat flour processed with fungal proteases and selected lactic acid bacteria was demonstrated to be safe for coeliac patients. This review article focuses on the biotechnologies that use selected sourdough lactic acid bacteria to potentially counteract the adverse reactions to gluten, and the risk of gluten contamination. PMID:28231160

The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus.

PubMed

Lv, You; Zhao, Xue; Guo, Weiying; Gao, Ying; Yang, Shuo; Li, Zhuo; Wang, Guixia

2018-01-01

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

PubMed

Kessler, Romain; Casan-Clara, Pere; Koehler, Dieter; Tognella, Silvia; Viejo, Jose Luis; Dal Negro, Roberto W; Díaz-Lobato, Salvador; Reissig, Karina; Rodríguez González-Moro, José Miguel; Devouassoux, Gilles; Chavaillon, Jean-Michel; Botrus, Pierre; Arnal, Jean-Michel; Ancochea, Julio; Bergeron-Lafaurie, Anne; De Abajo, Carlos; Randerath, Winfried J; Bastian, Andreas; Cornelissen, Christian G; Nilius, Georg; Texereau, Joëlle B; Bourbeau, Jean

2018-01-01

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients. Copyright ©ERS 2018.

Genes and post-term birth: late for delivery.

PubMed

Schierding, William; O'Sullivan, Justin M; Derraik, José G B; Cutfield, Wayne S

2014-10-14

Recent evidence suggests that prolonged pregnancies beyond 42 weeks of gestation (post-term births) are associated with long-term adverse health outcomes in the offspring. There is evidence that post-term birth has not only environmental causes, but also significant heritability, suggesting genetic and/or epigenetic influences interact with environmental cues to affect gestational length. As prolonged gestation is associated with adverse short- and long-term outcomes in the offspring, further research into the underlying genetic and epigenetic causes of post-term birth could be of importance for improving obstetric management.

Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings.

PubMed

Misiak, Błażej; Krefft, Maja; Bielawski, Tomasz; Moustafa, Ahmed A; Sąsiadek, Maria M; Frydecka, Dorota

2017-04-01

There is a growing body of research focused on the relationship between childhood trauma and the risk of developing psychosis. Numerous studies, including many large-scale population-based studies, controlling for possible mediating variables, provide persuasive evidence of a dose-response association and are indicative of a causal relationship. Existing evidence supports the specificity model, showing differential associations between particular adversities and clinical symptoms, with cumulative adversity causing less favorable clinical and functional outcomes in psychotic patients. To date, several psychological and biological models have been proposed to search for underlying developmental trajectories leading to the onset of psychosis, influencing psychopathological manifestation and negative functional outcomes due to a history of childhood trauma. In this article, we provide a unified review on the relationship between childhood trauma and psychosis by integrating results of epidemiological, clinical, neuropsychological and biological studies. The question whether psychosis with a positive history of childhood trauma should be considered as a new psychotic phenotype, requiring specific therapeutic interventions, warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity.

PubMed

Castelo-Branco, Frederico Silva; de Lima, Evanoel Crizanto; Domingos, Jorge Luiz de Oliveira; Pinto, Angelo C; Lourenço, Maria Cristina S; Gomes, Karen Machado; Costa-Lima, Mariana Marques; Araujo-Lima, Carlos Fernando; Aiub, Claudia Alessandra Fortes; Felzenszwalb, Israel; Costa, Thadeu Estevam M M; Penido, Carmen; Henriques, Maria G; Boechat, Nubia

2018-02-25

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. In this work, we synthesized two series of new acylhydrazides and evaluated their activity against different strains of Mtb. Derivatives of isoniazid (INH) showed important anti-Mtb activity, some being more potent than all anti-TB drugs of first choice. Moreover, three compounds proved to be more potent than INH against resistant Mtb. The Ames test showed favorable results for two of these substances compared to INH, one of which presented expressly lower toxicity to HepG2 cells than that of INH. This result shows that this compound has the potential to overcome one of the main adverse effects of this drug. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Impact of air pollutants on athletic performance

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

Pierson, W.E.

Human controlled and observational studies both lead to the conclusion of air pollution adversely affecting athletic performance during training and competition. The dosage of various air pollutants during exercise is much higher due to the marked increase in ventilatory rate and concomitant nasal and oral breathing. This is particularly true for sulfur dioxide which is a highly water-soluble gas and is normally absorbed in the upper airway during nasal breathing. With heavy exercise, oral pharyngeal breathing is the predominant mode of breathing and much larger amounts of sulfur dioxide are delivered to the lower airway resulting in significant impact uponmore » the lower respiratory tract. More recently, several controlled human studies have shown that a combination of exercise and air pollutants such as ozone (O3) or sulfur dioxides (SO2) cause a significant increase in bronchoconstriction and air flow obstruction when compared to the same exposure at rest. In strenuous athletic competition such as the Olympic Games where small increments of time often determine the ultimate success of athletes, the impact of air pollutants and subsequent adverse ventilatory changes can affect athletic performance. 62 references.« less

Ceftazidime-induced thrombocytopenia.

PubMed

Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M

2017-12-01

Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

New drugs and new toxicities: pembrolizumab-induced myocarditis.

PubMed

Inayat, Faisal; Masab, Muhammad; Gupta, Sorab; Ullah, Waqas

2018-01-23

Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

PubMed

Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N

2014-04-15

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2015-01-01

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

Adverse event reporting in cancer clinical trial publications.

PubMed

Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

2014-01-10

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

An Enduring Health Risk of Childhood Adversity: Earlier, More Severe, and Longer Lasting Work Disability in Adult Life.

PubMed

Laditka, Sarah B; Laditka, James N

2018-02-08

Childhood adversity has been linked with adult health problems. We hypothesized that childhood adversity would also be associated with work limitations due to physical or nervous health problems, known as work disability. With data from the Panel Study of Income Dynamics (PSID) (1968-2013; n=6,045; 82,374 transitions; 129,107 person-years) and the 2014 PSID Childhood Retrospective Circumstances Study, we estimated work disability transition probabilities with multinomial logistic Markov models. Four or more adversities defined a high level. Microsimulations quantified adult work disability patterns for African American and non-Hispanic white women and men, accounting for age, education, race, sex, diabetes, heart disease, obesity, and sedentary behavior. Childhood adversity was significantly associated with work disability. Of African American women with high adversity, 10.2% had moderate work disability at age 30 versus 4.1% with no reported adversities; comparable results for severe work disability were 5.6% versus 1.9% (both p<0.01). Comparable results for whites were 11.3% versus 4.7%, and 3.5% versus 1.1% (p<0.01). The association of childhood adversity with work disability remained significant after adjusting for diabetes, heart disease, obesity, and sedentary behavior (p<0.05). Childhood adversity may increase work disability throughout adult life. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adverse drug reactions in hospitalized Colombian children.

PubMed

de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

2016-09-30

The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p = 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p = 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

What can we do in secondary prevention of cigarette smoking?

PubMed

Haustein, Knut-Olaf

2003-12-01

Cigarette smoking kills about six million smokers per year worldwide, and the cigarette has become a symbol of threat to mankind, particularly in industrialized countries. Tobacco smoking causes signs of addiction due to nicotine, but it is the inhaled and exhaled smoke that causes damage to health if cigarette smoking is continued for one or more decades. It is very difficult to attain a high efficacy of stopping smoking using methods of primary prevention in children and young adults. Secondary and tertiary prevention methods use medical and psychological support to the smoker (behavioural and aversion therapy) as well as medical advice in combination with drugs such as nicotine replacement or bupropion. Using a combination of these methods can increase effectiveness up to 45%. Use of nicotine replacement therapy (NRT) in combination with medical advice is the method of smoking cessation recommended by the World Health Organization. Bupropion causes several severe side effects which are not observed with NRT. This article reviews various NRT formulations, including chewing gum, patch, nasal spray, tablet and inhaler, and our experience of using NRT in medical practice, such as adverse events, withdrawal symptoms and the efficacy of NRT in patients with coronary heart disease (angina pectoris, cardiac arrhythmias, etc.), are briefly mentioned. Overall, we need greater efforts in practising primary and secondary prevention among current and future physicians to solve the health problems associated with tobacco use in many nations.