A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care

PubMed Central

Jamison, Robert N.; Dorado, Kathleen; Mei, Anna; Edwards, Robert R.; Martel, Marc O.

2017-01-01

Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care. PMID:29392205

20 CFR Appendix 1 to Subpart P of... - Listing of Impairments

Code of Federal Regulations, 2013 CFR

2013-04-01

... review standard in §§ 404.1594 and 416.994). I. Effects of Treatment 1. General. Treatments for musculoskeletal disorders may have beneficial effects or adverse side effects. Therefore, medical treatment..., symptoms, and laboratory abnormalities of the disorder, and in terms of any side effects that may further...

20 CFR Appendix 1 to Subpart P of... - Listing of Impairments

Code of Federal Regulations, 2014 CFR

2014-04-01

... review standard in §§ 404.1594 and 416.994). I. Effects of Treatment 1. General. Treatments for musculoskeletal disorders may have beneficial effects or adverse side effects. Therefore, medical treatment..., symptoms, and laboratory abnormalities of the disorder, and in terms of any side effects that may further...

20 CFR Appendix 1 to Subpart P of... - Listing of Impairments

Code of Federal Regulations, 2012 CFR

2012-04-01

... review standard in §§ 404.1594 and 416.994). I. Effects of Treatment 1. General. Treatments for musculoskeletal disorders may have beneficial effects or adverse side effects. Therefore, medical treatment..., symptoms, and laboratory abnormalities of the disorder, and in terms of any side effects that may further...

Novel therapies in advanced renal cell carcinoma: management of adverse events from sorafenib and sunitinib.

PubMed

Ivanyi, Philipp; Winkler, Thomas; Ganser, Arnold; Reuter, Christoph; Grünwald, Viktor

2008-03-01

Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targeted therapies have distinct and specific side effects. Selective review in Medline and the data base of the American Society of Clinical Oncology on the treatment and side effects of tyrosine kinase inhibitors in renal cell carcinoma, drawing on the authors' own experience. Tyrosine kinase inhibitors are characterized by a variety of uncommon side effects, such as lassitude, mucosal inflammation and skin changes. The detection and treatment of adverse events are critical for interdisciplinary cancer treatment in order to ensure patients' safety. This article offers an overview of the unwanted effects of drug therapy in the management of renal cell carcinoma.

Antimicrobial Active Clothes Display No Adverse Effects on the Ecological Balance of the Healthy Human Skin Microflora

PubMed Central

Hoefer, Dirk; Hammer, Timo R.

2011-01-01

The progressive public use of antimicrobial clothes has raised issues concerning skin health. A placebo-controlled side-to-side study was run with antimicrobial clothes versus fabrics of similar structure but minus the antimicrobial activity, to evaluate possible adverse effects on the healthy skin microflora. Sixty volunteers were enrolled. Each participant received a set of form-fitting T-shirts constructed in 2 halves: an antibacterial half, displaying activities of 3–5 log-step reductions due to silver-finishes or silver-loaded fibres and a nonantibacterial control side. The microflora of the scapular skin was analyzed weekly for opportunistic and pathogenic microorganisms over six weeks. The antibacterial halves did not disturb the microflora in number or composition, whereas a silver-containing deodorant displayed a short-term disturbance. Furthermore, parameters of skin morphology and function (TEWL, pH, moisture) did not show any significant shifts. In summary, antimicrobial clothes did not show adverse effects on the ecological balance of the healthy skin microflora. PMID:22363849

"Side effects" of ECT are mainly depressive phenomena and are independent of age.

PubMed

Brodaty, H; Berle, D; Hickie, I; Mason, C

2001-10-01

The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.

Attention Deficit Disorder with Hyperactivity

DTIC Science & Technology

1991-01-01

fewer side effects and is the drug of choice (Shaywitz & Shaywitz, 1984). Pemoline is considered a second line drug due to possible hepatic adverse...which require this behavior (Barkley, 1977). The primary side effects observed with stimulants include insomnia, anorexia, weight loss or irritability...These side effects appear to be transitory and tend to disappear with a reduction in drug dosage (Barkley, 1977). Amery, Minichello and Brown (1984

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

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

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

Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

PubMed

Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

2016-06-01

Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

The dark side of browning.

PubMed

Tamucci, Kirstin A; Namwanje, Maria; Fan, Lihong; Qiang, Li

2018-02-01

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Adverse Behavioral Effects in Individuals with Mental Retardation and Mood Disorders Treated with Carbamazepine.

ERIC Educational Resources Information Center

Friedman, Debra L.; And Others

1992-01-01

This study with 65 individuals with mental retardation and additional seizure and/or psychiatric or behavioral disorders found that 9.2 percent experienced medication (carbamazepine) side effects, ranging from irritability to mania. More side effects were experienced by individuals with behavioral or psychiatric disorders than by those with an…

Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

PubMed

Nieschlag, Eberhard; Vorona, Elena

2015-09-01

Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

The safety of tocolytics used for the inhibition of preterm labour.

PubMed

Lamont, Callum D; Jørgensen, Jan Stener; Lamont, Ronald F

2016-09-01

Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Adverse breast cancer treatment effects: the economic case for making rehabilitative programs standard of care.

PubMed

Schmitz, Kathryn H; DiSipio, Tracey; Gordon, Louisa G; Hayes, Sandra C

2015-06-01

The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side effects. Two hundred eighty-seven Australian women diagnosed with early-stage breast cancer were prospectively followed starting at 6 months post-surgery for 12 months, with three monthly assessments of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data, and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. More than 90 % of women experienced at least one adverse effect (i.e., post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue, or weight gain). On average, women paid $5,636 (95 % confidence interval (CI), $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p < 0.05). Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

Keefe, John R.; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

Remediation of negative side effects of an on-going response-cost system with chronic mental patients.

PubMed

Doty, D W; McInnis, T; Paul, G L

1974-01-01

Response-cost procedures within a token economy with extremely regressed residents excluded many residents from access to positive reinforcement. Procedures allowing residents to "purchase eligibility" to obtain backup reinforcers through contingent payment on standing fines, combined with proportional fine payoff schedules contingent upon time without new fines, increased payment on fines, reduced incidence of new fines, and increased utilization of backup reinforcers. These modifications removed adverse side effects while retaining the benefits associated with response costs. Failures or adverse effects of elements of token systems should not occasion abandonment of token economies, but rather encourage their continual evaluation and modification.

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

PubMed

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

2014-06-01

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

Effects of Video Games on the Adverse Corollaries of Chemotherapy in Pediatric Oncology Patients: A Single-Case Analysis.

ERIC Educational Resources Information Center

Kolko, David J.; Rickard-Figueroa, Jorge L.

1985-01-01

Assessed effects of video games on adverse corollaries of chemotherapy in three pediatric oncology patients. Results indicated that access to video games resulted in reduction in the number of anticipatory symptoms experienced and observed, as well as a diminution in the aversiveness of chemotherapy side effects. (Author/NRB)

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

PubMed

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

2009-11-01

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

Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.

PubMed

Gur, Serap; Kadowitz, Philip J; Hellstrom, Wayne Jg

2013-01-01

Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown. The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available. Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.

A comparison of latanoprost monotherapy with a combination therapy of timolol/dorzolamide in patients with primary open-angle glaucoma.

PubMed

Caça, Ihsan; Simsek, Hüseyin; Unlü, Kaan; Ari, Seyhmus; Keklikçi, Ugur

2006-01-01

We compared latanoprost monotherapy therapy with timolol/ dorzolamide in patients with primary open-angle glaucoma to evaluate the effects on intraocular pressure (IOP) and occurrence of adverse events. IOP and topical side effects were evaluated at the beginning, first, and third months. Mean IOP was decreased at the third month. The most common side effect was hyperemia (43.6%). We concluded that latanoprost reduces IOP better than fixed combination and its topical side effects are tolerable.

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

PubMed

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

2009-07-01

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

A study of side-effects of Pandemrix® influenza (H1N1) vaccine on board a Norwegian naval vessel.

PubMed

Munch, Johan Storm; Johnsen, Bjørn Helge; Birkeland, Ingelin; Finne, Morten; Utkilen, Torun; Bøe, Tommy; Mjølhus, Gry; Sommerfelt-Pettersen, Jan

2010-01-01

The frigate His Norwegian Majesty's ship (HNoMS) Fridtjof Nansen was participating in operations in the Gulf of Aden in support of the EU mission tasked with protecting vessels from the threat of piracy. The crew was therefore prioritized and given the first batch of Influenza A (H1N1) vaccine (Pandemrix(®)). To investigate the type, frequency, and intensity of side effects after whole-crew vaccination with Pandemrix vaccine in healthy subjects in a controlled environment. A hundred and thirty-three members of the crew were vaccinated, and then they participated in the study. The side effects of the vaccination were evaluated through a survey. Seventy-five per cent of the vaccinated sailors reported adverse reactions to the vaccine, with 9% not being able to perform their daily duties for one day. Muscle pain, headaches, malaise, and fatigue were the most frequent symptoms reported. The vaccination program using Pandemrix H1N1 vaccine resulted in a high rate of side effects, which were generally mild and resolved within a few days. No serious lasting side effects of the vaccination were reported or registered. The adverse effects of the vaccination did not affect the operational capacity of the vessel.

Influenza vaccine adverse event and effect on acceptability in pediatric residents.

PubMed

Kara, Ates; Devrim, Ilker; Celik, Tolga; Akca, Tulay; Tezer, Hasan; Simsek, Ozlem Pelin; Kutluk, Tezer; Kale, Gulsev; Secmeer, Gulten

2007-11-01

Despite the demonstrated benefits of influenza vaccinations, the coverage is lower than expected among health-care personnel (HCP). In this study we surveyed the attitudes of pediatric residents regarding influenza immunization and adverse reactions. Forty-five female and 35 male pediatric residents with ages ranging from 24 to 28 years were vaccinated with an influenza vaccine on 2 days in the 3rd week of September 2005 by the same nurse. Among our resident, 27 (33.7%) thought the vaccine unnecessary; their vaccine coverage was only 12% in the previous year. Thirteen residents (16%) had soreness at the vaccination site; 7 (8%) had other local reactions that did not interfere with everyday activities, and 16 (20%) had any systemic side effects. The overall rate of side effects from the vaccination was 36.5% (n=29). Twenty of the 29 vaccinees who experienced side effects stated they did not want to receive the vaccine the following year because of the side effects, while 13% in the group without side effects stated the same thing, mainly because of the cost of vaccination. We would like to recommend an influenza vaccination campaign for HCP by employers, but first we must plan to take steps to improve the acceptability of the influenza vaccine among HCP.

The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

PubMed

Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

2017-09-01

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

Effects of road traffic noise and the benefit of access to quietness

NASA Astrophysics Data System (ADS)

Öhrström, E.; Skånberg, A.; Svensson, H.; Gidlöf-Gunnarsson, A.

2006-08-01

Socio-acoustic surveys were carried out as part of the Soundscape Support to Health research programme to assess the health effects of various soundscapes in residential areas. The study was designed to test whether having access to a quiet side of one's dwelling enhances opportunities for relaxation and reduces noise annoyance and other adverse health effects related to noise. The dwellings chosen were exposed to sound levels from road traffic ranging from about L=45-68 dB at the most-exposed side. The study involved 956 individuals aged 18-75 years. The results demonstrate that access to quiet indoor and outdoor sections of one's dwelling supports health; it produces a lower degree and extent of annoyance and disturbed daytime relaxation, improves sleep and contributes to physiological and psychological well-being. Having access to a quiet side of one's dwelling reduces disturbances by an average of 30-50% for the various critical effects, and corresponds to a reduction in sound levels of ( LAeq,24h) 5 dB at the most-exposed side. To protect most people (80%) from annoyance and other adverse effects, sound levels from road traffic should not exceed ( LAeq,24h) 60 dB at the most-exposed side, even if there is access to a quiet side of one's dwelling ( LAeq,24h⩽45 dB).

Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy.

PubMed

Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael

2015-11-06

Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.

Novel Opioid Analgesics and Side Effects.

PubMed

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

2017-08-16

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

Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: A report of 12 cases.

PubMed

Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

2016-12-01

Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change.

Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease

PubMed Central

Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

2016-01-01

Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change. PMID:27930569

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

The Reliability of the Scale for the Evaluation and Identification of Seizures, Epilepsy, and Anticonvulsant Side Effects-B

ERIC Educational Resources Information Center

Matson, Johnny L.; Laud, Rinita B.; Gonzalez, Melissa L.; Malone, Carrie J.; Swender, Stephen L.

2005-01-01

The use of anti-epileptic medications (AEDs) is much higher in individuals with intellectual disabilities than in the general population. As many of these individuals rely on such medications, clinicians should consider psychometrically sound instruments for assessing adverse side effects of these medications as one aspect of routine clinical…

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder.

PubMed

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

2017-01-01

Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient's predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = -0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = -0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. Trial Number NCT01072344 at ClinicalTrials.gov. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

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

[Side effects of treatment with the long-acting gonadorelin agonist triptorelin in a case of paraphilia].

PubMed

Hoogeveen, J H; van der Veer, E

2007-01-01

A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regimen needs to be revised.

The impact of polypharmacy on the health of Canadian seniors.

PubMed

Reason, Ben; Terner, Michael; Moses McKeag, Ali; Tipper, Brenda; Webster, Greg

2012-08-01

Prescription medication use increases with age. Seniors face an increased risk of adverse drug reactions from medications, partly because the kidneys and liver can lose functional ability with increasing age, resulting in the need for changes in dosage. To use population survey data to understand the extent and impact of multiple medication use and adverse drug events among Canadian seniors. This study consists of analysis of data from the Canadian Survey of Experiences with Primary Health Care, which was conducted through telephone by Statistics Canada in 2008. These analyses focussed on the 3132 respondents who were ≥ 65 years of age. Twenty-seven per cent of seniors reported taking five or more medications on a regular basis. Within the past year, 12% of seniors taking five or more medications experienced a side effect that required medical attention compared with 5% of seniors taking only one or two medications. Even when controlling for age and number of chronic conditions, the number of prescription medications was associated with the rate of emergency department use. Less than half of all seniors reported having received medication reviews and having the possible side effects of their prescription medications explained to them by their physician. Many Canadian seniors have an elevated risk of adverse events due to taking a high number of prescription medications and not having the potential side effects and drug interactions explained to them. There are interventions that can potentially reduce polypharmacy and adverse events, including routine medication reviews.

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Patterns of benzylpiperazine/trifluoromethylphenylpiperazine party pill use and adverse effects in a population sample in New Zealand.

PubMed

Wilkins, Chris; Sweetsur, Paul; Girling, Melissa

2008-11-01

A large legal market for party pills containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) developed in New Zealand after 2004. The use of these party pills has been associated with adverse health effects. The purpose of this paper was to assess a general population sample of party pill users to investigate the relationship between (1) patterns of use of BZP/TFMPP party pills and concurrent use of other drug types, and (2) adverse side effects from BZP/TFMPP party pill use. A national household survey of the use of BZP/TFMPP party pills was conducted using a computer-assisted telephone interviewing (CATI) facility. The quantity of BZP and TFMPP in each brand of party pill was obtained from the National Poisons Centre. Multiple logistic regression analysis was used to identify independent predictors of having experienced adverse side effects from party pills. The mean quantity of BZP/TFMPP taken on an occasion of greatest use was 533 mg (median 400 mg, range 43-2500 mg). Being female, using cannabis and other drugs concurrently with BZP/TFMPP party pills, taking large quantities of party pills in a single session and taking 5-hydroxytryptophan (5-HTP) recovery pills at the same time as party pills were independent predictors of having experienced an adverse problem from party pills. Females may be at greater risk of experiencing problems from BZP/TFMPP party pills due to their smaller physical size. Taking 5-HTP 'recovery' pills with party pills may increase the risk of adverse effects as both substances increase users' levels of serotonin.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

PubMed

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

PubMed Central

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-12-01

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

Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men.

PubMed

Perez-Mora, Nicolas; Velasco, Carlos; Bermüdez, Fernando

2015-01-01

Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients.

An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine.

PubMed

Wauters, Robert H; Hernandez, Camellia L; Petersen, Maureen M

2017-09-19

Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia

PubMed Central

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

Background While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012–2013. Methods The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Findings Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Conclusions Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control. PMID:28339462

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia.

PubMed

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

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

PubMed

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

2009-01-01

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

The efficacy in melasma treatment using a 1410 nm fractional photothermolysis laser.

PubMed

Wanitphakdeedecha, R; Keoprasom, N; Eimpunth, S; Manuskiatti, W

2014-03-01

Melasma treatment modalities including topical and procedural therapy have been employed with variable results and high recurrence rate. To quantitatively assess improvement in melasma and side effects after 1410 nm fractional photothermolysis laser treatments and to determine efficacy at 1-, 2- and 3-month follow-up after treatment. Thirty volunteers with melasma were treated with 1410 nm fractional photothermolysis for four passes on full face and additional four passes on melasma area. They were randomly treated on one side of their face with 20 mJ at 5% coverage and the other side of their face with 20 mJ at 20% coverage. All subjects were treated monthly for five times. Melanin index, Visual analogue scale and Melasma Area and Severity Index score were measured at baseline and 1-, 2- and 3-month follow-up after complete treatment protocol. There was statistically significant improvement of Melanin index at 2- and 3-month follow-up visits, but not at 1-month follow-up visit. Visual analogue scale and Melasma Area and Severity Index score improved significantly on both sides at 1-, 2- and 3-month follow-ups. The overall patients' satisfaction was significantly higher on the side treated with 20 mJ, 5% coverage. Adverse reactions included erythema, dryness and post-inflammatory hyperpigmentation on melasma area. Those side effects were significantly more intense on the side treated with 20 mJ, 20% coverage. 1410 nm fractional photothermolysis laser treatment is a safe and temporary effective procedure for melasma; however, long-term follow-up is still needed. Only 5% coverage should be used to minimize risks of adverse effects. © 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.

PubMed

Hoogeveen, John; Van der Veer, Eveline

2008-03-01

There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. We report a case of hormonal treatment of paraphilia that was associated with side effects. A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.

[Toxic effects of medications on the cornea].

PubMed

Ravet, O

2007-01-01

We reviewed the most recent systemic drugs used in Belgium causing toxic corneal side effects. These adverse reactions are rarely specific and often ignored or unknown. This description can help the physician's evaluation for a better interdisciplinary approach.

GraphSAW: a web-based system for graphical analysis of drug interactions and side effects using pharmaceutical and molecular data.

PubMed

Shoshi, Alban; Hoppe, Tobias; Kormeier, Benjamin; Ogultarhan, Venus; Hofestädt, Ralf

2015-02-28

Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases. The system is able to analyze single and combined drug-drug interactions, drug-molecule interactions as well as single and cumulative side effects. In addition, it allows exploring associative networks of drugs, molecules, metabolic pathways, and diseases in an intuitive way. The molecular medication analysis includes the capabilities of the upper features. A statistical evaluation of the integrated data and top 20 drugs concerning drug interactions and side effects is performed. The results of the data analysis give an overview of all theoretically possible drug interactions and side effects. The evaluation shows a mismatch between pharmaceutical and molecular databases. The concordance of drug interactions was about 12% and 9% of drug side effects. An application case with prescribed data of 11 patients is presented in order to demonstrate the functionality of the system under real conditions. For each patient at least two interactions occured in every medication and about 8% of total diseases were possibly induced by drug therapy. GraphSAW (http://tunicata.techfak.uni-bielefeld.de/graphsaw/) is meant to be a web-based system for health professionals and researchers. GraphSAW provides comprehensive drug-related knowledge and an improved medication analysis which may support efforts to reduce the risk of medication errors and numerous drastic side effects.

Cutaneous Side-effects of Immunomodulators in MS.

PubMed

Lebrun, C; Bertagna, M; Cohen, M

2011-09-01

Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.

Childhood lymphoblastic leukemia adverse drug reactions: study of risk factors and therapy prognosis by optical methods

NASA Astrophysics Data System (ADS)

Zyubin, A.; Lavrova, A.; Babak, S.; Malaschenko, V.; Borisova, A.; Opryshko, N.

2016-10-01

The treatment of acute lymphoblastic leukemia (ALL) can result in the side-effects such as kidney affection, hepatic failure and tissue hypoxia. We study dynamics of special biochemical marker of these pathologies - adenosine triphosphate, that is well-known substance of energy metabolism. We use methods of confocal microscopy for determining the cellular and mitochondrial concentration of adenosine triphosphate (ATP). Quantitative values of adenosine triphosphate were calculated for each patient and correlation with degree of side-effects had been done. The application of confocal microscopy for studying of side-effects and therapy of lymphoblastic leukemia is discussed.

Dofetilide

MedlinePlus

... than normal) If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/ ...

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

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

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

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

PubMed

Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence, side effects and awareness about energy drinks among the female university students in Saudi Arabia

PubMed Central

Rahamathulla, Mohamudha Parveen

2017-01-01

Objective: To evaluate the consumption, prevalence, side effects and awareness of energy drinks among female university students in Saudi Arabia. Methods: A quantitative research design was implied with sample size of 358 female students, recruited from Prince Sattam bin Abdulaziz University. The data, gathered through self-administered questionnaire, was analyzed through SPSS version 20.0 with p value <0.005 deemed statistically significant. Results: From the sample of 358 female students, 337 attempted the questionnaire from which 274 students were identified as energy drink consumers. The reasons for increased consumption of energy drinks mainly include giving company to friends (59.4%), better performance in exams (41.2%), and better concentration in studies (39.4%). The most common side effect was headache (32.3%), and the least was identified as allergy (2%). Only 39.4% and 29.9% of students acquired awareness regarding the harmful effects of energy drink consumption during pregnancy and breast feeding respectively. Conclusion: A significant proportion of female students at Prince Sattam bin Abdulaziz have reported to consume energy drinks regularly with several adverse effects. The government of Saudi Arabia should take serious initiatives towards organizing effective awareness programs specifically in universities and colleges to control the consumption of energy drinks and educate on the adverse effects. PMID:28523035

Prevalence, side effects and awareness about energy drinks among the female university students in Saudi Arabia.

PubMed

Rahamathulla, Mohamudha Parveen

2017-01-01

To evaluate the consumption, prevalence, side effects and awareness of energy drinks among female university students in Saudi Arabia. A quantitative research design was implied with sample size of 358 female students, recruited from Prince Sattam bin Abdulaziz University. The data, gathered through self-administered questionnaire, was analyzed through SPSS version 20.0 with p value <0.005 deemed statistically significant. From the sample of 358 female students, 337 attempted the questionnaire from which 274 students were identified as energy drink consumers. The reasons for increased consumption of energy drinks mainly include giving company to friends (59.4%), better performance in exams (41.2%), and better concentration in studies (39.4%). The most common side effect was headache (32.3%), and the least was identified as allergy (2%). Only 39.4% and 29.9% of students acquired awareness regarding the harmful effects of energy drink consumption during pregnancy and breast feeding respectively. A significant proportion of female students at Prince Sattam bin Abdulaziz have reported to consume energy drinks regularly with several adverse effects. The government of Saudi Arabia should take serious initiatives towards organizing effective awareness programs specifically in universities and colleges to control the consumption of energy drinks and educate on the adverse effects.

How to introduce demand side resources in the design of low-carbon power systems in China

NASA Astrophysics Data System (ADS)

Zhou, Pengcheng; Liu, Yiqun; Zeng, Ming; Sun, Chenjun

2018-04-01

Nowadays, China's energy demand sustained rapid growth, and the coal-based energy structure has adverse effects on the environment. The flexibility of demand side resource (DSR) will be greatly improved, and DSR can reduce electricity consumption actively and temporarily, and realize energy saving and emission reduction. But there are still some problems to introduce DSR in China. This paper proposes three practices for introducing demand side resources to improve the flexibility of power systems through demand resources.

Bifidobacterium lactis B94 plus inulin for Treatment of Helicobacter pylori infection in children: does it increase eradication rate and patient compliance?

PubMed

Islek, A; Sayar, E; Yilmaz, A; Artan, R

2015-01-01

The aim of this study is to investigate the effects of Bifidobacterium lactis B94 and inulin (synbiotic) treatment on eradication rate and patient compliance in subjects treated for symptomatic H. pylori infection. Patients with symptomatic H. pylori infection were divided into two groups. One group was treated with standard triple therapy (lansoprazole, amoxicillin, and clarithromycin) and B. lactis B94 (5 × 109 CFU/dose) plus inulin (900 mg) twice daily for seven days. The control group was treated with standard triple therapy and placebo. The side effects and eradication rates were evaluated at the end of the study. Ninety-three patients with H. pylori infection were treated with either synbiotic plus triple therapy (n = 47) or placebo plus triple therapy (n = 46). The infection eradication rates were not significantly different between the synbiotic and placebo groups [intent-to-treat (ITT), 80.8% and 67.3%, p = 0.13, respectively; per-protocol (PP), 86.3% and 81.5%, p = 0.55, respectively]. The drug side effects were significantly higher in the placebo group than in the synbiotic group (63% and 17%, respectively, p < 0.01). Although no intolerable adverse side effects were observed in the synbiotic group, intolerable adverse side effects were observed in 13% of the placebo group (p = 0.01). Our results suggest that twice daily 5 × 109 CFU/dose B. lactis B94 plus 900 mg inulin treatment did not have a direct positive effect on the H. pylori eradication rate. However, this treatment had significantly reduced side effects and indirectly increased eradication rates by increasing patient compliance. © Acta Gastro-Enterologica Belgica.

Before you install exterior wood-based siding

Treesearch

Mark T. Knaebe

1995-01-01

Moisture accumulation and extreme fluctuations in moisture levels can adversely affect the service life of components, such as wood siding and windows. Adverse moisture conditions can induce checking, warping, paint failure, and in severe cases, rotting of the wood.

Words or numbers? Communicating risk of adverse effects in written consumer health information: a systematic review and meta-analysis.

PubMed

Büchter, Roland Brian; Fechtelpeter, Dennis; Knelangen, Marco; Ehrlich, Martina; Waltering, Andreas

2014-08-26

Various types of framing can influence risk perceptions, which may have an impact on treatment decisions and adherence. One way of framing is the use of verbal terms in communicating the probabilities of treatment effects. We systematically reviewed the comparative effects of words versus numbers in communicating the probability of adverse effects to consumers in written health information. Nine electronic databases were searched up to November 2012. Teams of two reviewers independently assessed studies. randomised controlled trials; verbal versus numerical presentation; context: written consumer health information. Ten trials were included. Participants perceived probabilities presented in verbal terms as higher than in numeric terms: commonly used verbal descriptors systematically led to an overestimation of the absolute risk of adverse effects (Range of means: 3% - 54%). Numbers also led to an overestimation of probabilities, but the overestimation was smaller (2% - 20%). The difference in means ranged from 3.8% to 45.9%, with all but one comparison showing significant results. Use of numbers increased satisfaction with the information (MD: 0.48 [CI: 0.32 to 0.63], p < 0.00001, I2 = 0%) and likelihood of medication use (MD for very common side effects: 1.45 [CI: 0.78 to 2.11], p = 0.0001, I2 = 68%; MD for common side effects: 0.90 [CI: 0.61 to 1.19], p < 0.00001, I2 = 1%; MD for rare side effects: 0.39 [0.02 to 0.76], p = 0.04, I2 = not applicable). Outcomes were measured on a 6-point Likert scale, suggesting small to moderate effects. Verbal descriptors including "common", "uncommon" and "rare" lead to an overestimation of the probability of adverse effects compared to numerical information, if used as previously suggested by the European Commission. Numbers result in more accurate estimates and increase satisfaction and likelihood of medication use. Our review suggests that providers of consumer health information should quantify treatment effects numerically. Future research should focus on the impact of personal and contextual factors, use representative samples or be conducted in real life settings, measure behavioral outcomes and address whether benefit information can be described verbally.

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Small for Gestational Age (SGA)

MedlinePlus

... Throat (ENT) Dental/Orthodontics Urology Orthopedics Child Development Psychology Special Education Services DO WE NEED TO IMPROVE ... body proportions and head circumference Improved psychological and cognitive function Possible Adverse Side Effects of GHT for ...

Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

PubMed

Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

2012-11-01

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Rufinamide

MedlinePlus

... unusual problems while taking this medication.If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/ ...

Erlotinib induced target-like purpura.

PubMed

Rungtrakulchai, R; Rerknimitr, P

2014-02-18

Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor, used as a treatment for advanced stage cancer. The most common side effect is cutaneous toxicity including the already known papulopustular reaction. We herein report a case of erlotinib induced target-like purpura, a peculiar cutaneous adverse event. A 57-year-old patient with advanced non-small cell lung cancer was treated by erolotinib 150 mg daily. After taking the drug for three days, an unusual target-like purpura developed on her lower legs. Skin biopsy specimen taken from the lesion revealed an extravasation of erythrocytes in the upper dermis without destruction of blood vessel walls. This skin eruption cleared after the drug was withdrawn and recurred after erlotinib was re-challenged. The mechanism underlying this cutaneous adverse event remains to be elucidated. Physicians should be aware of the rare side effect of this increasingly used drug.

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

PubMed Central

Miyaoka, Tsuyoshi; Tsuji, Seiichi; Inami, Yasushi; Nishida, Akira; Horiguchi, Jun

2010-01-01

Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. Data Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized. Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem. PMID:21494350

Molecular targeted therapies for solid tumors: management of side effects.

PubMed

Grünwald, Viktor; Soltau, Jens; Ivanyi, Philipp; Rentschler, Jochen; Reuter, Christoph; Drevs, Joachim

2009-03-01

This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available. Copyright 2009 S. Karger AG, Basel.

Identifying and managing the adverse effects of immune checkpoint blockade

PubMed Central

Winer, Arthur; Bodor, J. Nicholas

2018-01-01

Immunotherapy has revolutionized the field of oncology. By inhibiting the cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1) immune checkpoint pathways, multiple studies have demonstrated greatly improved survival in locally advanced and metastatic cancers including melanoma, renal, lung, gastric, and hepatocellular carcinoma. Trials in other malignancies are ongoing, and undoubtedly the number of drugs in this space will grow beyond the six currently approved by the Food and Drug Administration. However, by altering the immune response to fight cancer, a new class of side effects has emerged known as immune-related adverse events (irAEs). These adverse events are due to overactivation of the immune system in almost any organ of the body, and can occur at any point along a patient’s treatment course. irAEs such as endocrinopathies (thyroiditis), colitis, and pneumonitis may occur more commonly. However, other organs such as the liver, heart, or brain may also be affected by immune overactivation and any of these side effects may become life threatening. This review presents an approach to promptly recognize and manage these toxicities, to hopefully minimize morbidity and mortality from irAEs. PMID:29593893

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru.

PubMed

Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

2011-01-01

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89), anemia (OR = 2.10; IC95%: 1.13-3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6), and smoking (OR = 2.00; 95%CI: 1.03-3.87) were independently associated with adverse drug reactions. Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.

A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly

PubMed Central

Wongrakpanich, Supakanya; Wongrakpanich, Amaraporn; Melhado, Katie; Rangaswami, Janani

2018-01-01

NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly. PMID:29392089

[Side Effects of Occupational Group Therapy].

PubMed

Flöge, B; Fay, D; Jöbges, M; Linden, M; Muschalla, B

2016-12-01

Background: Occupational therapy is an important co-therapy in psychiatric therapy. It is a common belief that no risks are associated with occupational therapy. Negative effects caused by group therapy, especially occupational therapy, have not been in the focus of research yet. In this study we want to illustrate possible types and intensities of group side effects through occupational therapy. Patients and Methods: Patients of an inpatient rehabilitation facility filled out the Adverse Treatment Reaction Group Checklist. The checklist contains 47 items divided in six dimensions: group size, content, group participants, group outcome and global. The self-rating used a 5-point likert scale (0 = not at all; 4 = very much, extremely stressful) and gives information about types and intensities of the side effects. Results: 88.9 % of 45 patients reported negative effects of occupational group therapy. 28.9 % of the patients rated the side effect as at least severe. Discussion: Occupational therapy is associated with side effects as every other group therapy. Possible side effects caused by group therapy should be considered while planning and implementing occupational therapy. © Georg Thieme Verlag KG Stuttgart · New York.

42 CFR 484.55 - Condition of participation: Comprehensive assessment of patients.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Standard: Drug regimen review. The comprehensive assessment must include a review of all medications the patient is currently using in order to identify any potential adverse effects and drug reactions, including ineffective drug therapy, significant side effects, significant drug interactions, duplicate drug...

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

PubMed Central

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

2010-01-01

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

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

PubMed Central

Ajaltouni, Jean

2015-01-01

The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

PubMed

Ageu, Luminiţa Ştefania; Levai, Codrina Mihaela; Andreescu, Nicoleta Ioana; Grigoraş, Mirela Loredana; Hogea, Lavinia Maria; Chiriac, Daniela Veronica; Folescu, Roxana; Bredicean, Ana Cristina; Nussbaum, Liliana Maria; Enătescu, Virgil Radu; Poroch, Vladimir; Lupu, Viorel; Puiu, Maria; Nussbaum, Laura Alexandra

2018-01-01

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

The role of intravenous immunoglobulin in treatment of mucous membrane pemphigoid: A review of literature

PubMed Central

Tavakolpour, Soheil

2016-01-01

Background: Mucous membrane pemphigoid (MMP) is considered an autoimmune blistering disease that predominantly affects mucous membranes. Various treatments are available for controlling the diseases, but not all of them may respond. Materials and Methods: PubMed and Google Scholar were searched for all the associated studies until 2015, using the keywords such as “cicatricial pemphigoid” or “ocular pemphigoid” or “mucous membrane pemphigoid” or “MMP” and “intravenous immunoglobulin” or “IVIg” to find all the relevant studies. The last search update was for September 2, 2015. Among the searched items, only English studies were included in the review. Results: After excluding nonrelevant studies, 13 studies with a total number of seventy patients with MMP who were under treatment with IVIg were analyzed. The 65 patients responded completely, one did not respond, two had partially responded, and the remaining two patients stopped IVIg therapy, which resulted in ocular cicatricial pemphigoid progression. Majority of the studies reported mild adverse effects while two of them did not report any unwanted side effect. The most common side effect was headache, followed by nausea. Most of the patients who had a cessation of IVIg therapy before achieving clinical remission experienced the disease progression. Conclusion: Overall, it can be concluded that IVIg therapy was very helpful in treatment of MMP patients who did not respond to conventional therapy or stopped using them for various side effects. Adverse effects associated with IVIg therapy were considerably lower than conventional therapy that can lead toward treatment with this agent in patients who suffer from severe side effects. PMID:27904583

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

PubMed

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

2017-04-01

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

Technical feasibility and revision efficacy of the sequential deployment of endoscopic bilateral side-by-side metal stents for malignant hilar biliary strictures: a multicenter prospective study.

PubMed

Lee, Tae Hoon; Park, Do Hyun; Lee, Sang Soo; Choi, Hyun Jong; Lee, Jun Kyu; Kim, Tae Hyeon; Kim, Jong Hyeok; Jeong, Seok; Park, Sang-Heum; Moon, Jong Ho

2013-02-01

Theoretically, the side-by-side bilateral placement of metal stents may be technically easier than stent-in-stent bilateral placement in stent revision. However, side-by-side placement can be technically challenging, as the deployment of the first stent can preclude the passage of the second stent. We explored the technical feasibility and revision efficacy of endoscopic bilateral side-by-side stent placement for malignant hilar biliary strictures. Forty-four patients with Bismuth type II or higher malignant hilar biliary strictures were enrolled in seven academic tertiary referral centers. Endoscopic placement of side-by-side bilateral metal stents with 7F thin delivery shaft was performed. The outcome measurements were the technical and functional success, adverse events, endoscopic revision success rate, and stent patency. Overall, the technical and functional success rates were 91 % (40/44), and 98 % (39/40), respectively. Two of the failed patients were converted successfully with subsequent contralateral stent-in-stent placement, and the other patients underwent percutaneous intervention. Early stent-related adverse events occurred in 10 %. The endoscopic revision rate due to stent malfunction during follow-up (median: 180 days) was 45 % (18/40; tumor ingrowth in 4 and in-stent sludge impaction/stone formation in 14 patients). The endoscopic revision success rate was 92 % (12/13). Five patients with comorbidity underwent initial percutaneous intervention. The median survival and stent patency periods were 180 and 157 days, respectively. The sequential placement of a metal stent with a 7F thin delivery shaft in bilateral side-by-side procedures may be feasible and effective for malignant hilar biliary strictures and for endoscopic stent revision.

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

PubMed

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

2018-05-01

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

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

PubMed

Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

2018-06-01

To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients.

PubMed

Rommer, Paulus S; Zettl, Uwe K

2018-04-01

Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

Large-scale exploration and analysis of drug combinations.

PubMed

Li, Peng; Huang, Chao; Fu, Yingxue; Wang, Jinan; Wu, Ziyin; Ru, Jinlong; Zheng, Chunli; Guo, Zihu; Chen, Xuetong; Zhou, Wei; Zhang, Wenjuan; Li, Yan; Chen, Jianxin; Lu, Aiping; Wang, Yonghua

2015-06-15

Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered. We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications. The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Safety of stable isotope use.

PubMed

Koletzko, B; Sauerwald, T; Demmelmair, H

1997-08-01

The increased employment of stable isotope tracers for diagnostic and research purposes frequently raises questions on potential risks associated with their use, which is of particular importance in the paediatric age group. Biological effects and the potential of adverse events has been evaluated in a large number of animal and, in part, also human studies. Possible differences in physical, chemical and biochemical behaviour resulting in kinetic and thermodynamic isotope effects between stable isotopes of the same element are related to the relative differences in atomic weight. Deuterium (2H), which differs markedly in mass from the predominant hydrogen isotope 1H, may induce serious side-effects at high concentrations in body fluids. The threshold dose for the occurrence of side-effects lies well above the usual tracer dosages for clinical use. In contrast to deuterium, heavier stable isotopes such as 13C, 15N or 18O that differ relatively little in mass from the predominant isotopes such as 12C, does not show any adverse biological effects even at highest enrichments. The doses of stable isotope tracer substances that are used for clinical diagnostic and research purposes appear safe and without any adverse effects. Stable isotope tracers should only be used in children if the trace is safe at the doses applied, and tracer is chemically pure and stable. In the case of intravenous application, the tracer preparation must also be sterile and pyrogen free.

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

PubMed Central

Oncel, Mehmet Yekta; Erdeve, Omer

2016-01-01

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects. PMID:26862505

Urolift - minimally invasive surgical BPH management.

PubMed

Pushkaran, Anish; Stainer, Victoria; Muir, Gordon; Shergill, Iqbal S

2017-03-01

An ideal treatment option for symptomatic Benign Prostatic Hyperplasia (BPH) should relieve lower urinary tract symptoms (LUTS) and restore Quality of Life (QoL). Currently available medical therapies and surgical options for symptomatic BPH have side effects that adversely affects quality of life. Prostatic urethral lift (PUL) is a novel endourology procedure that promises to relieve LUTS without the aforementioned side effects. Areas covered: We diligently reviewed all the published literature on PUL, till July 2016 using standard search criteria. Expert commentary: There is good quality evidence to establish the efficiency of PUL in treating symptomatic BPH without adversely affecting the QoL. Based on the current literature, PUL can be considered as an option for those symptomatic BPH patients with small or medium size prostates (< 80 ml) without median lobe enlargement, who failed on medical therapy or are intolerant to it and wish to preserve their sexual function.

Managing the oral side-effects of medications used to treat multiple sclerosis.

PubMed

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-06-01

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

[Integration of nutritional care into cancer treatment: need for improvement].

PubMed

Joly, Caroline; Jacqueline-Ravel, Nathalie; Pugliesi-Rinaldi, Angela; Bigler-Perrotin, Lucienne; Chikhi, Marinette; Dietrich, Pierre-Yves; Dulguerov, Pavel; Miralbell, Raymond; Picard-Kossovsky, Michel; Seium, Yodit; Thériault, Michel; Pichard, Claude

2011-11-16

Progresses in cancer treatment transformed cancer into a chronic disease associated with growing nutritional problems. Poor nutritional status of cancer patients worsens morbidity, mortality, overall cost of care and decreases patients' quality of life, oncologic treatments tolerance and efficacy. These adverse effects lead to treatment modifications or interruptions, reducing the chances to control or cure cancer. Implementation of an interdisciplinary and longitudinal integration of nutritional care and nutritional information into cancer treatment (The OncoNut Program) could prevent or treat poor nutritional status and its adversely side effects.

Delayed adverse reactions to the parenteral administration of iodinated contrast media.

PubMed

Egbert, Robert E; De Cecco, Carlo N; Schoepf, U Joseph; McQuiston, Andrew D; Meinel, Felix G; Katzberg, Richard W

2014-12-01

This article presents an overview of delayed adverse reactions (DARs) to parenteral iodinated contrast media and discusses the clinical nature, risk factors, mechanisms, and potential economic implications of these DARs. DARs to contrast media are not rare but are often not recognized as being linked to contrast administration and may be falsely ascribed to other drugs. These side effects are problematic because the patient is usually without medical supervision.

77 FR 3646 - Products Containing Imidazolines Equivalent to 0.08 Milligrams or More

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... congestion and/or ophthalmic irritation. Products containing imidazolines can cause serious adverse reactions... unpredictable, idiosyncratic reaction (i.e., a drug effect that occurs in a small number of people due to age..., and death associated with cardiac reactions in adults. Other systemic side effects can include...

Low-level laser/light therapy for androgenetic alopecia.

PubMed

Gupta, Aditya K; Lyons, Danika C A; Abramovits, William

2014-01-01

Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies.

Ethambutol

MedlinePlus

... doctor immediately: blurred vision inability to see the colors red and green sudden changes in vision skin rash itching If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

Dermatitis toxica faciei after boric acid.

PubMed

Jiráková, Anna; Rajská, Lucie; Rob, Filip; Gregorová, Jana; Hercogová, Jana

2015-01-01

An adverse toxic reaction to the topical application of a 2% boric acid solution is described in a 2-year-old girl. Topical boric acid is licensed for use in children above the age of 10 in the Czech Republic. However, it can be bought over the counter and it is very often used in younger children. Due to its fast absorption and slow elimination, there is a high risk of systemic side effects. On the other hand, topical side effects are not reported in the present literature. © 2014 Wiley Periodicals, Inc.

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851

A comparison between monophasic levonorgestrel-ethinyl estradiol 150/30 and triphasic levonorgestrel-ethinyl estradiol 50-75-125/30-40-30 contraceptive pills for side effects and patient satisfaction: a study in Iran.

PubMed

Kashanian, Maryam; Shahpourian, Farangis; Zare, Omolbanin

2010-05-01

Oral contraceptive pills (OCPs) are one of the most effective reversible and accessible contraceptives, and patient acceptance for their use depends partly on the unfavorable adverse effects. The present study compared the two kinds of OCPs (monophasic; levonorgestrel (LNG)-ethinyl estradiol (EE) 150/30 versus triphasic; LNG-EE 50-75-125/30-40-30) for adverse effects and patient satisfaction. A randomized clinical trial was performed on 314 women who used OCPs for the first time, as their contraception, for 6 months. Overall, 1884 cycles were studied. In the monophasic group (n=159 who finally finished the study), monophasic pills LNG-EE 150/30mcg, and in the triphasic group (n=155 who finally finished the study), triphasic pills LNG-EE 50-75-125/30-40-30 mcg were used. Statistical analysis was performed using SPSS 10: Chi square test, Fisher exact test and Student's t-test were used. There were no significant differences between the two groups for common side effects, including nausea, headache, nervousness, facial hyperpigmentation (chloasma), and body weight (increase or decrease) but breakthrough bleeding and spotting (BTB/S) were less in the triphasic group, occurring in 30 cycles (18.86%) versus 10 cycles (6.45%), P=0.009*. Patient satisfaction for the two OCPs was similar and high. The rates of side effects were low. It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects; therefore there is no benefit of one over the other except for BTB/S, for which triphasic is superior. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Contraceptive knowledge, perceptions, and concerns among men in Uganda.

PubMed

Thummalachetty, Nityanjali; Mathur, Sanyukta; Mullinax, Margo; DeCosta, Kelsea; Nakyanjo, Neema; Lutalo, Tom; Brahmbhatt, Heena; Santelli, John S

2017-10-10

Low contraceptive uptake and high unmet need for contraception remain significant issues in Uganda compared to neighboring countries such as Kenya, Ethiopia, and Rwanda. Although prior research on contraceptive uptake has indicated that male partners strongly influence women's decisions around contraceptive use, there is limited in-depth qualitative research on knowledge and concerns regarding modern contraceptive methods among Ugandan men. Using in-depth interviews (N = 41), this qualitative study investigated major sources of knowledge about contraception and perceptions of contraceptive side effects among married Ugandan men. Men primarily reported knowledge of contraceptives based on partner's experience of side effects, partner's knowledge from health providers and mass media campaigns, and partner's knowledge from her peers. Men were less likely to report contraceptive knowledge from health care providers, mass media campaigns, or peers. Men's concerns about various contraceptive methods were broadly associated with failure of the method to work properly, adverse health effects on women, and severe adverse health effects on children. Own or partner's human immunodeficiency virus (HIV) status did not impact on contraceptive knowledge. Overall, we found limited accurate knowledge about contraceptive methods among men in Uganda. Moreover, fears about the side effects of modern contraceptive methods appeared to be common among men. Family planning services in Uganda could be significantly strengthened by renewed efforts to focus on men's knowledge, fears, and misconceptions.

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

PubMed

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

2016-01-01

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

A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

PubMed

Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

2006-05-01

Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg. These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.

[Analgesics in geriatric patients. Adverse side effects and interactions].

PubMed

Gosch, Markus

2015-07-01

Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions.

A survey of the awareness, knowledge and behavior of hair dye use in a korean population with gray hair.

PubMed

Kim, Jung Eun; Jung, Hee Dam; Kang, Hoon

2012-08-01

Gray hair naturally develops in the process of human aging. Many people with gray hair periodically dye their hair. Hair dyeing products are widely used and they can cause adverse effects. Therefore, the user's knowledge and recognition about hair dyeing and related side effects are important. The goal of this study was to lay the foundation for understanding, preventing and treating side effects caused by hair coloring products. We conducted a questionnaire survey for adult males and females aged over 20 who had gray hair. A total of 500 subjects were included in this study and statistical analysis was performed. Large numbers of the people who had experience with hair dye (233 out of 319 people, 73.0%) did not know about the exact brand name of the hair dye product that they were using. Of 319 hair dye users, 23.8% (76 out of 319) people stated that they experienced side effects. Despite the occurrence of side effects from hair dyeing products, it seems they did not realize the seriousness of the side effects or the need for treatment. It is advisable to introduce a system that enables users to become aware of the ingredients and side effects of hair coloring products and give opportunities for users to become aware of the side effects of hair coloring through education, publicity and publication of an informational booklet.

Evidence-based clinical update: Which local anesthetic drug for pediatric caudal block provides optimal efficacy with the fewest side effects?

PubMed

Dobereiner, Elisabeth F A; Cox, Robin G; Ewen, Alastair; Lardner, David R

2010-12-01

The purpose of this evidence-based clinical update is to identify the best evidence when selecting a long-acting local anesthetic agent for single-shot pediatric caudal anesthesia in children. A structured literature search was conducted using PubMed and Medline (OVID) using the terms "caudal" and combinations of at least two of "bupivacaine", "ropivacaine", and "levobupivacaine". The search limits included "randomized controlled trials" (RCTs), "meta-analysis", "evidence-based reviews" or "reviews", "human", and "all child: 0-18 yr". Seventeen RCTs were identified that concerned single-shot pediatric caudal anesthesia with at least two of the three drugs in question. Data were extracted for the areas of clinical efficacy and side effects. Study findings were assigned levels of evidence, and grades of recommendation were made according to Centre for Evidence-Based Medicine criteria. The three drugs investigated were found to be equivalent in terms of efficacy. Evidence showed bupivacaine with the highest incidence of motor block and ropivacaine with the lowest. Adverse effects were rare and unrelated to the choice of drug. There were no serious adverse events. None of the three agents was shown to be superior in terms of efficacy. Bupivacaine is preferred if motor block is desired, ropivacaine is preferred if motor block is to be minimized. Adverse effects in human studies are rare, mild, and unrelated to the choice of drug. Despite encountering the absence of serious adverse events in each of the studies reviewed, it is noted that animal studies suggest a safer profile with ropivacaine or levobupivacaine than with bupivacaine.

Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV Positive Patients in Imam Khomeini Hospital of Tehran, Iran.

PubMed

Koochak, Hamid E; Babaii, Azita; Pourdast, Alia; Golrokhy, Raheleh; Rasoolinejad, Mehrnaz; Khodaei, Sepideh; Moghadam, Saeed R J; Taheri, Reza R; Seyed Alinaghi, Seyed Ahmad

2017-01-01

The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Flurbiprofen Ophthalmic

MedlinePlus

... call your doctor immediately: bleeding within the eye sensitivity to light eye pain blurry, cloudy, or blocked areas of vision If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

Predicting drug side-effect profiles: a chemical fragment-based approach

PubMed Central

2011-01-01

Background Drug side-effects, or adverse drug reactions, have become a major public health concern. It is one of the main causes of failure in the process of drug development, and of drug withdrawal once they have reached the market. Therefore, in silico prediction of potential side-effects early in the drug discovery process, before reaching the clinical stages, is of great interest to improve this long and expensive process and to provide new efficient and safe therapies for patients. Results In the present work, we propose a new method to predict potential side-effects of drug candidate molecules based on their chemical structures, applicable on large molecular databanks. A unique feature of the proposed method is its ability to extract correlated sets of chemical substructures (or chemical fragments) and side-effects. This is made possible using sparse canonical correlation analysis (SCCA). In the results, we show the usefulness of the proposed method by predicting 1385 side-effects in the SIDER database from the chemical structures of 888 approved drugs. These predictions are performed with simultaneous extraction of correlated ensembles formed by a set of chemical substructures shared by drugs that are likely to have a set of side-effects. We also conduct a comprehensive side-effect prediction for many uncharacterized drug molecules stored in DrugBank, and were able to confirm interesting predictions using independent source of information. Conclusions The proposed method is expected to be useful in various stages of the drug development process. PMID:21586169

[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.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

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

PubMed Central

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

2018-01-01

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

Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

PubMed

Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

2015-11-01

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rauwolfia in the Treatment of Hypertension.

PubMed

Lobay, Douglas

2015-06-01

Rauwolfia serpentina is a safe and effective treatment for hypertension. The plant was used by many physicians throughout India in the 1940s and then was used throughout the world in the 1950s, including in the United States and Canada. It fell out of popularity when adverse side effects, including depression and cancer, became associated with it. This author reviews the scientific literature with regard to the use of Rauwolfia and the treatment of hypertension. The author reviews the plant's botany, chemistry, and pharmacology and provides a researched and documented method of action for the active ingredients. With special emphasis on the plant's role in treating high blood pressure, the author looks at medical uses of the plant, critically examining its adverse side effects, toxicology, and carcinogenicity. The author refutes the association between the plant and carcinogenicity and discusses the importance of correct dosing and of screening patients to minimize the occurrence of depression. He concludes with the recommendation of use of low dose Rauwolfia (LDR) for suitable patients with hypertension. The plant provides clinicians with a safe and effective adjunct to pharmaceuticals in the treatment of high blood pressure.

Feasibility of transcranial direct current stimulation use in children aged 5 to 12 years.

PubMed

Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Allegro, Juleilda Valéria Brasil Nunes; Neto, Carlos Eduardo Borges Passos; Lucena, Rita de Cássia Saldanha; Fregni, Felipe

2014-10-01

Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. © The Author(s) 2013.

New concept for treating female stress urinary incontinence with radiofrequency.

PubMed

Lordelo, Patrícia; Vilas Boas, Andrea; Sodré, Danielle; Lemos, Amanda; Tozetto, Sibele; Brasil, Cristina

2017-01-01

To evaluate the clinical response and adverse effects of radiofrequency on the urethral meatus in the treatment of stress urinary incontinence in women. This phase one study included ten women with Stress Urinary Incontinence (SUI). The evaluation consisted of 1 hour Pad tests to quantify urine loss and to assess the degree of procedure satisfaction by using the Likert scale. To evaluate safety, we observed the number of referred side effects. Average age was 53.10 years±7.08 years. In assessing the final Pad Test, 70% showed a reduction and 30% a worsening of urinary loss. Using the Pad Test one month later, there was a reduction in all patients (p=0.028). The degree of satisfaction was 90% and no side effects have been observed. One patient reported burning sensation. The treatment of SUI with radiofrequency on the urethral meatus has no adverse effects, being a low risk method that reduces urinary loss in women. However, to increase the validity of the study, larger clinical trials are warranted. Copyright® by the International Brazilian Journal of Urology.

New concept for treating female stress urinary incontinence with radiofrequency

PubMed Central

Lordelo, Patrícia; Boas, Andrea Vilas; Sodré, Danielle; Lemos, Amanda; Tozetto, Sibele; Brasil, Cristina

2017-01-01

ABSTRACT Purpose: To evaluate the clinical response and adverse effects of radiofrequency on the urethral meatus in the treatment of stress urinary incontinence in women. Materials and Methods: This phase one study included ten women with Stress Urinary Incontinence (SUI). The evaluation consisted of 1 hour Pad tests to quantify urine loss and to assess the degree of procedure satisfaction by using the Likert scale. To evaluate safety, we observed the number of referred side effects. Results: Average age was 53.10 years±7.08 years. In assessing the final Pad Test, 70% showed a reduction and 30% a worsening of urinary loss. Using the Pad Test one month later, there was a reduction in all patients (p=0.028). The degree of satisfaction was 90% and no side effects have been observed. One patient reported burning sensation. Conclusion: The treatment of SUI with radiofrequency on the urethral meatus has no adverse effects, being a low risk method that reduces urinary loss in women. However, to increase the validity of the study, larger clinical trials are warranted. PMID:28727373

Medications and Adverse Voice Effects.

PubMed

Nemr, Kátia; Di Carlos Silva, Ariana; Rodrigues, Danilo de Albuquerque; Zenari, Marcia Simões

2017-08-16

To identify the medications used by patients with dysphonia, describe the voice symptoms reported on initial speech-language pathology (SLP) examination, evaluate the possible direct and indirect effects of medications on voice production, and determine the association between direct and indirect adverse voice effects and self-reported voice symptoms, hydration and smoking habits, comorbidities, vocal assessment, and type and degree of dysphonia. This is a retrospective cross-sectional study. Fifty-five patients were evaluated and the vocal signs and symptoms indicated in the Dysphonia Risk Protocol were considered, as well as data on hydration, smoking and medication use. We analyzed the associations between type of side effect and self-reported vocal signs/symptoms, hydration, smoking, comorbidities, type of dysphonia, and auditory-perceptual and acoustic parameters. Sixty percent were women, the mean age was 51.8 years, 29 symptoms were reported on the screening, and 73 active ingredients were identified with 8.2% directly and 91.8% indirectly affecting vocal function. There were associations between the use of drugs with direct adverse voice effects, self-reported symptoms, general degree of vocal deviation, and pitch deviation. The symptoms of dry throat and shortness of breath were associated with the direct vocal side effect of the medicine, as well as the general degree of vocal deviation and the greater pitch deviation. Shortness of breath when speaking was also associated with the greatest degree of vocal deviation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.

PubMed

Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I; Gutzmer, Ralf; Utikal, Jochen S; Göppner, Daniela; Hassel, Jessica C; Meier, Friedegund; Tietze, Julia K; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard; Heinzerling, Lucie M

2016-06-01

Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Safety of Acupuncture in Patients with Cancer Therapy–Related Thrombocytopenia

PubMed Central

Cybularz, Paul A.; Brothers, Karen; Singh, Gurneet M.; Feingold, Jennifer L.; Niesley, Michelle L.

2015-01-01

Abstract Background: Acceptance of acupuncture as an efficacious integrative modality for oncology-related side-effect management is rapidly expanding. It is imperative that guidelines regarding safe treatment supported by clinical experience are established. Oncology patients frequently experience thrombocytopenia as a side-effect of chemotherapy or radiation. However, safety data for acupuncture in adult patients with cancer who are thrombocytopenic is lacking. Materials and Methods: The medical records of 684 patients who received acupuncture treatments in an established acupuncture program at a private cancer treatment hospital were reviewed for adverse events occurring within the context of thrombocytopenia. Results: Of 2135 visits eligible for evaluation, 98 individual acupuncture visits occurred in patients with platelet counts <100,000/μL, including nine visits in which platelet counts were <50,000/μL. No adverse events of increased bruising or bleeding were noted. Medications and nutritional supplements or botanicals that may influence coagulation were also tabulated, with no apparent adverse events in this patient population. Conclusions: Discrepancies in the literature highlight the need to create cohesive safety guidelines backed by clinical research, specifically for groups at higher risk for adverse events. The preliminary evidence put forth in this study lays the foundation that supports the notion that acupuncture can be used safely with a high-need oncology population within an integrated model of care. In this descriptive retrospective case series of adult oncology patients with thrombocytopenia, no adverse events of increased bruising or bleeding were documented. Prospective trials are needed to confirm these initial observations. PMID:26401193

Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

PubMed Central

Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

2011-01-01

Background Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. Methodology and Results A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions. Conclusions Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients. PMID:22110689

A rare case of imatinib-induced erythroderma

PubMed Central

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

2013-01-01

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

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

PubMed Central

Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

2015-01-01

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

Probable Gastrointestinal Toxicity of Kombucha Tea

PubMed Central

Srinivasan, Radhika; Smolinske, Susan; Greenbaum, David

1997-01-01

Kombucha tea is a health beverage made by incubating the Kombucha “mushroom” in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association. PMID:9346462

Probable gastrointestinal toxicity of Kombucha tea: is this beverage healthy or harmful?

PubMed

Srinivasan, R; Smolinske, S; Greenbaum, D

1997-10-01

Kombucha tea is a health beverage made by incubating the Kombucha "mushroom" in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association.

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.

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

PubMed

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

2009-12-01

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

Effect of Riblets on Pressure Recovery in a Straight-Walled Diffuser

DTIC Science & Technology

1990-12-01

in the boundary layer velocity pro - file. As the flow continues to oppose the adverse pressure gradient, the fluid near the wall begins to flow in the...and was 37 inches long. The floor and ceiling of the test section were con - 3 structed of wood and the side panels were made of plexiglass. Both side...the diffuser remained fairly con - stant at 52 percent. The riblet results seem to follow the same trend, providing an approximate 35 percent increase in

[Effectiveness and safety of atosiban vs. pulsatile administration of fenoterol in the treatment of preterm labour].

PubMed

Nonnenmacher, A; Hopp, H; Dudenhausen, J

2009-10-01

The aim of this study was to compare the efficacy and side effects of atosiban with those of fenoterol (pulsatile administration) for acute tocolysis. A prospective, open-label, randomised controlled trial was performed. Patients in preterm labour at 24+0 to 33+6 weeks of gestation were randomised to receive atosiban (A) or fenoterol (F) pulsatile administration. Primary outcome was the arrest of preterm labour. The proportion of woman remaining undelivered at 48 hours (86.3% atosiban group and 79.6% fenoterol group) and at 7 days (78.4% vs. 66.7%) was comparable. The incidence of maternal cardiovascular side effects was lower in the atosiban group (4% vs. 78%, p=0.0). Tocolysis was terminated as a result of maternal adverse effects in the fenoterol group (9%). Fetal tachycardia was lower in the atosiban group (2% vs. 22%). The mean duration of tocolytic administration was lower in the atosiban group (19 h vs. 24.5 h, p<0.05). The adverse effects in the pulsatile administration of fenoterol for short duration were only dependent on the initial dosage for the arrest of preterm labour. Neonatal outcome were similar between the treatment groups and were rather related to the gestational age not to the tocolytic agent. Atosiban was comparable in clinical effectiveness and was associated with fewer maternal and fetal adverse effects, so that fenoterol cannot be recommended. Completion of tocolytic therapy 12 hours after arrest of preterm labour is effective and associated with a short mean duration. Georg Thieme Verlag KG Stuttgart-New York.

Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?

PubMed Central

Yanto, Theo Audi; Kosasih, Felicia Nathania

2018-01-01

Background Metformin is widely known as an antidiabetic agent which has significant gastrointestinal side effects, but nightmares and abnormal dreams as its adverse reactions are not well reported. Case Presentation Herein we present a case of 56-year-old male patient with no known history of recurrent nightmares and sleep disorder, experiencing nightmare and abnormal dreams directly after consumption of 750 mg extended release metformin. He reported his dream as an unpleasant experience which awakened him at night with negative feelings. The nightmare only lasted for a night, but his dreams every night thereafter seemed abnormal. The dreams were vivid and indescribable. The disappearance and occurrence of abnormal dreams ensued soon after the drug was discontinued and rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR) probability scale and resulted as probable causality. Conclusion Metformin might be the underlying cause of nightmare and abnormal dreams in this patient. More studies are needed to confirm the association and causality of this findings. PMID:29581904

Adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting.

PubMed

Lee, Erica B; Amin, Mina; Egeberg, Alexander; Wu, Jashin J

2018-05-06

Apremilast, a phosphodiesterase-4 inhibitor, is an oral therapy for treatment of psoriasis. Its safety profile is favorable, with side effects including diarrhea, nausea, vomiting, depression, and weight decrease, primarily based on clinical trial data. However, limited research exists on the side effect frequency and subsequent adverse events (AEs) in real-world practice. This retrospective chart review included patients who presented to the dermatology clinic at Kaiser Permanente Los Angeles Medical Center and were treated with apremilast at any time between January 1, 2015 and January 11, 2018. Patients were not included if they did not have at least one follow-up by clinic visit, telephone, or email correspondence after being prescribed apremilast. A total of 77 patients were included. AEs and withdrawal due to AEs were assessed throughout the treatment period from each patient's respective medical record. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of safety in clinical use of generic paclitaxel [NK] for injection.

PubMed

Tsukiyama, Ikuto; Hotta, Kazuo; Takeuchi, Masayuki; Onishi, Masahumi; Toyama, Yukio; Saito, Hiroko; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Hasegawa, Takaaki

2012-04-01

The introduction of generic drugs is a favored strategy in reducing medical costs, but some clinicians are often reluctant to use them because of lack of information with regard to their side effects. Generic paclitaxel [NK] differs from the proprietary version, Taxol®, in containing added citric acid and a more pure form of castor oil. However, little information exists regarding the effects of these additives on adverse events such as vascular pain, phlebitis, hypersensitivity and hepatic dysfunction. To compensate for this lack of information and to validate the safety of using generic paclitaxel, we investigated adverse events in response to generic paclitaxel [NK]. Our investigation focused on patients treated with both the proprietary formulation (Taxol® for injection) and the generic version(paclitaxel [NK] for injection)sequentially from April 2008 to March 2009. Adverse events were investigated retrospectively. Incidence of vascular pain, phlebitis and hypersensitivity was similar to that with the original product. Although the expression of some liver enzymes was slightly increased and some gastrointestinal events were reduced following generic paclitaxel [NK] treatment there was no statistically significant difference. The profiles of other adverse events were not significantly different. Increased vascular pain and phlebitis, predicted due to low pH conditions caused by citric acid, were not observed. Similarly, the pure castor oil included in generic paclitaxel [NK] did not influence hypersensitivity and hepatic function. We found no significant differences in our study of proprietary and generic paclitaxel [NK]. Thus, clinicians have no reason for prejudice against using generic paclitaxel [NK] on the basis of increased risk of side effects.

Nurses' discourse in contraceptive prescribing: an analysis using Foucault's 'procedures of exclusion'.

PubMed

Hayter, Mark

2007-05-01

This paper is a report of an analysis of the discourse about contraceptive efficacy and side effects used by nurses when prescribing contraception. All women seeking contraception should be informed of the efficacy and potential adverse effects of the particular method they are considering. This information facilitates an informed choice. Women also require this information in order to monitor for any side effects. Paradoxically, side effects are also a key factor in reducing adherence with contraceptive regimens. However, there is no literature that explores specifically how this issue is addressed in clinical consultations, or places these practices in a theoretical context. Forty-nine consultations between nurses and women in sexual health clinics were audio-recorded during 2002. Data were subject to a discourse analysis using Foucault's 'procedures of exclusion' to explore the discursive construction of contraceptive efficacy and side effects The nurses employed specific discursive strategies when discussing contraception. When addressing efficacy, discourse centred on medico-statistical facts, but side effects were described in lay terms that minimized their severity. Nurses contextualized contraceptive side effects within potential problems that women might experience in pregnancy, and also attempted to 'normalize' contraceptive-related problems. Discourse and its deployment play a key role in practitioner-client relationships that sexual health nurses need to become more aware of how they discuss clinical issues about contraception with women. Clinical data on contraceptive side-effects are present in the literature, and it is important that sexual health nurses use this to help women make truly informed decisions.

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

PubMed

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

2008-01-01

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

Leveraging graph topology and semantic context for pharmacovigilance through twitter-streams.

PubMed

Eshleman, Ryan; Singh, Rahul

2016-10-06

Adverse drug events (ADEs) constitute one of the leading causes of post-therapeutic death and their identification constitutes an important challenge of modern precision medicine. Unfortunately, the onset and effects of ADEs are often underreported complicating timely intervention. At over 500 million posts per day, Twitter is a commonly used social media platform. The ubiquity of day-to-day personal information exchange on Twitter makes it a promising target for data mining for ADE identification and intervention. Three technical challenges are central to this problem: (1) identification of salient medical keywords in (noisy) tweets, (2) mapping drug-effect relationships, and (3) classification of such relationships as adverse or non-adverse. We use a bipartite graph-theoretic representation called a drug-effect graph (DEG) for modeling drug and side effect relationships by representing the drugs and side effects as vertices. We construct individual DEGs on two data sources. The first DEG is constructed from the drug-effect relationships found in FDA package inserts as recorded in the SIDER database. The second DEG is constructed by mining the history of Twitter users. We use dictionary-based information extraction to identify medically-relevant concepts in tweets. Drugs, along with co-occurring symptoms are connected with edges weighted by temporal distance and frequency. Finally, information from the SIDER DEG is integrate with the Twitter DEG and edges are classified as either adverse or non-adverse using supervised machine learning. We examine both graph-theoretic and semantic features for the classification task. The proposed approach can identify adverse drug effects with high accuracy with precision exceeding 85 % and F1 exceeding 81 %. When compared with leading methods at the state-of-the-art, which employ un-enriched graph-theoretic analysis alone, our method leads to improvements ranging between 5 and 8 % in terms of the aforementioned measures. Additionally, we employ our method to discover several ADEs which, though present in medical literature and Twitter-streams, are not represented in the SIDER databases. We present a DEG integration model as a powerful formalism for the analysis of drug-effect relationships that is general enough to accommodate diverse data sources, yet rigorous enough to provide a strong mechanism for ADE identification.

Worldwide Survey of Nonmedical Drug Use and Alcohol Use among Military Personnel: 1980.

DTIC Science & Technology

1980-11-14

unlimited IS SUPPLEMENTARY NOTES Prepared with assistance of: Yukiko Carnies and Edward Farley 19. KEY WORDS (Continua on rovers* side It necea" and IdentIy...158 IV. ALCOHOL USE ................................. 161 Prevalence of Alcohol Use ..................... 161 Adverse Physiological Effects of...FURTHER RESEARCH REQUIRED ................... 276 Determine the Proportion of Servicemembers with Impaired Military Effectiveness ....... 276

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

PubMed

Sabbatini, F; Minieri, M; Manzi, G; Piai, G; D'Angelo, V; Mazzacca, G

1991-01-01

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

Efficacy of autologous platelet-rich plasma combined with fractional ablative carbon dioxide resurfacing laser in treatment of facial atrophic acne scars: A split-face randomized clinical trial.

PubMed

Faghihi, Gita; Keyvan, Shima; Asilian, Ali; Nouraei, Saeid; Behfar, Shadi; Nilforoushzadeh, Mohamad Ali

2016-01-01

Autologous platelet-rich plasma has recently attracted significant attention throughout the medical field for its wound-healing ability. This study was conducted to investigate the potential of platelet-rich plasma combined with fractional laser therapy in the treatment of acne scarring. Sixteen patients (12 women and 4 men) who underwent split-face therapy were analyzed in this study. They received ablative fractional carbon dioxide laser combined with intradermal platelet-rich plasma treatment on one half of their face and ablative fractional carbon dioxide laser with intradermal normal saline on the other half. The injections were administered immediately after laser therapy. The treatment sessions were repeated after an interval of one month. The clinical response was assessed based on patient satisfaction and the objective evaluation of serial photographs by two blinded dermatologists at baseline, 1 month after the first treatment session and 4 months after the second. The adverse effects including erythema and edema were scored by participants on days 0, 2, 4, 6, 8, 15 and 30 after each session. Overall clinical improvement of acne scars was higher on the platelet-rich plasma-fractional carbon dioxide laser treated side but the difference was not statistically significant either 1 month after the first treatment session (P = 0.15) or 4 months after the second (P = 0.23). In addition, adverse effects (erythema and edema) on the platelet-rich plasma-fractional carbon dioxide laser-treated side were more severe and of longer duration. Small sample size, absence of all skin phototypes within the study group and lack of objective methods for the evaluation of response to treatment and adverse effects were the limitations. This study demonstrated that adding platelet-rich plasma to fractional carbon dioxide laser treatment did not produce any statistically significant synergistic effects and also resulted in more severe side effects and longer downtime.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Assessment of the use of sialogogues in the clinical management of patients with xerostomia.

PubMed

Chainani-Wu, Nita; Gorsky, Meir; Mayer, Priscilla; Bostrom, Alan; Epstein, Joel B; Silverman, Sol

2006-01-01

This study was conducted to assess the clinical efficacy and adverse effects of pilocarpine, bethanechol and cevimeline in patients with xerostomia. In this open-label crossover assessment in 20 patients with xerostomia, a one- to two-week course of each medication with a one-week washout period was prescribed. Side effects, symptoms, whole stimulated and unstimulated saliva were measured. Each sialogogue was found to increase saliva and decrease symptoms. A mixed-effects analysis showed a greater increase in stimulated saliva on bethanechol compared to pilocarpine (0.106, p = 0.0272). Increased sweating was the most common side effect, experienced more frequently with pilocarpine as compared to bethanechol (p = 0.0588) or cevimeline (p = 0.0143). A carryover effect beyond the washout period was seen. Effects on saliva and side effects vary between sialogogues, suggesting a benefit of trials with different sialogogues to determine individual patient preference. The observed carryover effect suggests that intermittent treatment may be an alternative to continuous treatment with sialogogues.

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

PubMed Central

Bohn, Laura M.

2016-01-01

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

Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.

PubMed Central

Manson, J M; Zolna, L E; Kang, Y J; Johnson, C M

1987-01-01

The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time. Images PMID:3662478

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial.

PubMed

von Au, Alexandra; Milloth, Eva; Diel, Ingo; Stefanovic, Stefan; Hennigs, Andre; Wallwiener, Markus; Heil, Joerg; Golatta, Michael; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Schuetz, Florian; Domschke, Christoph

2016-01-01

Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness. In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter. Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts. We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

Tranexamic acid use during total hip arthroplasty: A single center retrospective analysis.

PubMed

Stoicea, Nicoleta; Moran, Kenneth; Mahmoud, Abdel-Rasoul; Glassman, Andrew; Ellis, Thomas; Ryan, John; Granger, Jeffrey; Joseph, Nicholas; Salon, Nathan; Ackermann, Wiebke; Rogers, Barbara; Niermeyer, Weston; Bergese, Sergio D

2018-05-01

Tranexamic acid (TXA) is an antifibrinolytic agent that has shown promise in reducing blood loss during total hip arthroplasty (THA). Several studies have reported side effects of high-dose TXA administration, including myocardial infarction (MI), thromboembolic events, and seizures. These possible side effects have prevented the widespread adoption of TXA in the surgical community. We conducted a retrospective chart review of 564 primary and revision THAs performed at a single academic center. Surgical patients received either no TXA or 1 g IV TXA at the beginning of surgery followed by a second bolus just before the surgical wound closure, at the surgeon's discretion. We analyzed differences in hemoglobin (Hb), hematocrit (Hct), estimated blood loss (EBL), and adverse events in patients receiving TXA versus patients not receiving TXA up to 2 days following surgery. Significantly higher Hb and Hct values were found across all time points among patients undergoing primary posterior or revision THA who had received TXA. In addition, transfusion rates were significantly decreased in both primary posterior THAs and revision THAs when TXA was administered. Patients who received TXA experienced significantly fewer adverse events than those who did not for all surgery types. Administration of low-dose intravenous (IV) and intra-articular (IA) TXA does not appear to increase rates of adverse events and may be effective in minimizing blood loss, as reflected by Hb and Hct values following THA.

Effects of Korean Red Ginseng extract on busulfan-induced dysfunction of the male reproductive system.

PubMed

Jung, Seok-Won; Kim, Hyeon-Joong; Lee, Byung-Hwan; Choi, Sun-Hye; Kim, Hyun-Sook; Choi, Yang-Kyu; Kim, Joon Yong; Kim, Eun-Soo; Hwang, Sung-Hee; Lim, Kwang Yong; Kim, Hyoung-Chun; Jang, Minhee; Park, Seong Kyu; Cho, Ik-Hyun; Nah, Seung-Yeol

2015-07-01

Anticancer agents induce a variety of adverse effects when administered to cancer patients. Busulfan is a known antileukemia agent. When administered for treatment of leukemia in young patients, busulfan could cause damage to the male reproductive system as one of its adverse effects, resulting in sterility. We investigated the effects of Korean Red Ginseng extract (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive system. We found that administration of busulfan to mice: decreased testis weight; caused testicular histological damage; reduced the total number of sperm, sperm motility, serum testosterone concentration; and eventually, litter size. Preadministration of KRGE partially attenuated various busulfan-induced damages to the male reproductive system. These results indicate that KRGE has a protective effect against busulfan-induced damage to the male reproduction system. The present study shows a possibility that KRGE could be applied as a useful agent to prevent or protect the male reproductive system from the adverse side effects induced by administration of anticancer agents such as busulfan.

Donor vigilance data of a blood transfusion service: A multicenter analysis.

PubMed

Burkhardt, T; Dimanski, B; Karl, R; Sievert, U; Karl, A; Hübler, C; Tonn, T; Sopvinik, I; Ertl, H; Moog, R

2015-10-01

Donor vigilance is an important part of the quality management system of blood transfusion services. The evaluation of donor side effects helps to improve the donation process and donor compliance. The aim of the present study was to evaluate donor vigilance data in whole blood and plasmapheresis donors of a blood donor service. Donors fulfilling current national and European eligibility criteria underwent whole blood and plasmapheresis donation (PCS and MCS+ (Haemonetics, Braintree, USA), A 200 (Fenwal, Round Lake, USA). Whole blood was collected at fixed and mobile sites while plasmaphereses were performed at 8 plasma centers. From 2011 to 2013 donor information was provided for gender, age, body weight, height, first and repeat donation. Donors were monitored for venipuncture and circulatory associated side effects. The total incidences of adverse events were 5004 (0.56%) in repeat donors and 2111 (2.78%) in first time donors for whole blood donation and 3323 (1.01%) and 514 (7.96%) for plasmaphereses, respectively. Circulatory associated events were 2679 (0.30%) for whole blood donation and 1624 (0.49%) for plasmaphereses. Our donor vigilance data of a blood transfusion service show that whole blood and plasmapheresis are safe with low incidences of adverse events. Repeat donation and age are predictors for low rates of adverse events. On the other hand, first time donation and female gender were associated with higher incidences of adverse events. Copyright © 2015 Elsevier Ltd. All rights reserved.

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Desmopressin Nasal

MedlinePlus

... you experience any unusual problems while using this medication.If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

A Systematic Approach to Alternative Medical Procedures

DTIC Science & Technology

2009-10-01

One potent source of sulfora - phane is broccoli sprouts, in which the sulforaphane concentration is more than an order of magnitude higher than in...mature broccoli . No adverse side effects have been reported from the use of broc- coli sprouts. Although individual extracts, sub- stances, or behaviors

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria].

PubMed

Kolarz, Gernot; Mayrhofer, Franz; Neumann, Kurt; Singer, Franz

2003-01-31

Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial.

PubMed

Simberkoff, Michael S; Arbeit, Robert D; Johnson, Gary R; Oxman, Michael N; Boardman, Kathy D; Williams, Heather M; Levin, Myron J; Schmader, Kenneth E; Gelb, Lawrence D; Keay, Susan; Neuzil, Kathleen; Greenberg, Richard N; Griffin, Marie R; Davis, Larry E; Morrison, Vicki A; Annunziato, Paula W

2010-05-04

The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth. To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults. Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration number: NCT00007501) 22 U.S. academic centers. 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy. Single dose of herpes zoster vaccine or placebo. Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants. After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients. Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always obtained. Herpes zoster vaccine is well tolerated in older, immunocompetent adults. Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.

Clinical experience with molindone hydrochloride in geriatric patients.

PubMed

Peper, M

1985-08-01

Elderly patients (N = 28) with a variety of psychiatric disorders were treated with molindone in an 8-week open clinical trial. Many patients had concomitant medical illnesses, and many were on other medications in addition to molindone. Molindone appeared to be safe, clinically effective, and well-tolerated. The most common adverse effects were extrapyramidal side effects, but the occurrence of these symptoms was relatively low.

Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.

PubMed

Le Naour, Morgan; Lunzer, Mary M; Powers, Michael D; Kalyuzhny, Alexander E; Benneyworth, Michael A; Thomas, Mark J; Portoghese, Philip S

2014-08-14

It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.

Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

PubMed

Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

2016-01-01

The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory related adverse effects. Finally, insufficient higher-order evidence to support the widespread use of medical marijuana was found, but a limited amount of moderate-level evidence supports its use in pain and seizure management. Published by Elsevier Inc.

Immunohistochemical Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients with Persistent Sexual Side Effects after Finasteride Use for Androgenetic Alopecia

PubMed Central

Di Loreto, Carla; La Marra, Francesco; Mazzon, Giorgio; Belgrano, Emanuele; Trombetta, Carlo; Cauci, Sabina

2014-01-01

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29–43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23–49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues. PMID:24959691

The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective.

PubMed

Al Omari, Ahmad I; Alzoubi, Firas Q; Alsalem, Mohammad M; Aburahma, Samah K; Mardini, Diala T; Castellanos, Paul F

Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years. VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively. This study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion. Series of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation. Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation. Seizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70-90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency. The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems. Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a superficial wound infection in one patient (3%) which was treated conservatively, none of the complications necessitated VNS removal. VNS appears to be an effective non-pharmacologic adjuvant therapy in patients with medically refractory seizures. With the favorable adverse-effect profile previously described, VNS is generally well tolerated and of a great benefit to such patients. Laryngeal side effects, of which hoarseness being of the greatest repetition, are the most common after the VNS implantation. VNS can affect the voice and reduced vocal cord motion on the implantation side with secondary supraglottic muscle tension. Otolaryngologists are not only capable of performing VNS implantation, but can also manage surgical complications, assess laryngeal side effects and treat them as needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Kerato-lenticular ocular deposits and visual impairment with prolonged chlorpromazine use: A case series.

PubMed

Gowda, Guru S; Hegde, Aditya; Shanbhag, Vandita; Narayanaswamy, Janardhanan C; Jaisoorya, T S

2017-02-01

Chlorpromazine is a low potency "typical" antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Ritalin: Education's Fix-It Drug?

ERIC Educational Resources Information Center

Divoky, Diane

1989-01-01

Describes the case of Casey Jesson, a hyperactive child ordered by the state of Hew Hampshire to ingest Ritalin or forego a public education. Despite adverse side effects and the perils of drug dependency, there is greater parental and educator acceptance of Ritalin than ever before. Scientologists are sparking an anti-Ritalin campaign. Includes…

Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment

ERIC Educational Resources Information Center

Erickson, Elizabeth; Sivasankar, Mahalakshmi

2010-01-01

Purpose: Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE),…

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

PubMed

Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M

2015-10-14

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.

Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

PubMed

Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

2015-08-01

Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of patients’ experiences with antidepressants reported by means of a medicine reporting system

PubMed Central

van Geffen, E. C. G.; van der Wal, S. W.; van Hulten, R.; de Groot, M. C. H.; Egberts, A. C. G.

2007-01-01

Objective To assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs). Methods All reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison. Results Of the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase. Conclusion Patients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice. PMID:17874086

Botulinum toxin injections for the treatment of hemifacial spasm over 16 years.

PubMed

Sorgun, Mine Hayriye; Yilmaz, Rezzak; Akin, Yusuf Alper; Mercan, Fatma Nazli; Akbostanci, Muhittin Cenk

2015-08-01

The aim of this study was to investigate the efficacy and side effects of botulinum toxin (BTX) in the treatment of hemifacial spasm (HFS). We also focused on the divergence between different injection techniques and commercial forms. We retrospectively evaluated 470 sessions of BTX injections administered to 68 patients with HFS. The initial time of improvement, duration and degree of improvement, and frequency and duration of adverse effects were analysed. Pretarsal and preseptal injections and Botox (Allergan, Irvine, CA, USA) and Dysport (Ipsen Biopharmaceuticals, Paris, France) brands were compared in terms of efficacy and side effects, accompanied by a review of papers which reported BTX treatment of HFS. An average of 34.5 units was used per patient. The first improvement was felt after 8 days and lasted for 14.8 weeks. Patients experienced a 73.7% improvement. In 79.7% of injections, no adverse effect was reported, in 4.9% erythema, ecchymosis, and swelling in the injection area, in 3.6% facial asymmetry, in 3.4% ptosis, in 3.2% diplopia, and in 2.3% difficulty of eye closure was detected. Patients reported 75% improvement on average after 314 sessions of pretarsal injections and 72.7% improvement after 156 sessions of preseptal injections (p=0.001). The efficacy and side effects of Botox and Dysport were similar. BTX is an effective and safe treatment option for HFS. No difference was determined between Botox and Dysport, and pretarsal injection is better than preseptal injection regarding the reported degree of improvement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicological Findings in 889 Fatally Injured Obese Pilots Involved in Aviation Accidents

DTIC Science & Technology

2010-05-01

fenfluramine has now been withdrawn from the drug markets due to its side effects , heart valve conditions, pulmonary hypertensions, and cardiac...adverse effects of excess visceral abdominal fat (4, 5, 34) . abdominal obesity has been linked with coronary heart disease (22) . the comorbidities...Methamphetamine Cocaine Δ9-Tetrahydrocannabinol (THC)/THC Carboxylic Acid Prescription Drugs Alprazolam Amitriptyline Amlodipine Atenolol Atropine

Synthetic Cannabis Overdose and Withdrawal in a Young Adult: A Case Report, Commentary on Regulation, and Review of the Literature.

PubMed

Samaan, John; Ferrer, Gerardo F; Akinyemi, Boye; Junquera, Patricia; Oms, Juan; Dumenigo, Rhaisa

2016-01-01

Introduction . Marijuana has been used for its psychotropic effects including enhanced relaxation and perceptual alterations. However, the use of synthetic marijuana (SM) leads to more frequent and drastic side effects than the typical use of regular marijuana, owing to the fact that SM has a shorter duration and an earlier peak of action. Despite all the potential adverse health effects associated with SM use, current health policies on SM are very limited. It is believed that the popularity of SM has increased, due to its easy accessibility in the US and lack of detection in typical urine drug screens for THC. Case Report . One case presented is of a young adult patient, with histories of recurrent synthetic cannabis and recreational cannabis use, who had developed drastic physiological and psychiatric symptoms, including the development of acute-onset psychosis. Conclusion/Discussion . This case, as many others nationwide, exemplifies the impact of synthetic cannabinoid use and abuse in adolescents. Side effects and adverse health consequences of synthetic cannabinoid use warrant stricter regulations and policies in order to decrease psychiatric hospital admissions and associated healthcare costs.

Rauwolfia in the Treatment of Hypertension

PubMed Central

Lobay, Douglas

2015-01-01

Rauwolfia serpentina is a safe and effective treatment for hypertension. The plant was used by many physicians throughout India in the 1940s and then was used throughout the world in the 1950s, including in the United States and Canada. It fell out of popularity when adverse side effects, including depression and cancer, became associated with it. This author reviews the scientific literature with regard to the use of Rauwolfia and the treatment of hypertension. The author reviews the plant’s botany, chemistry, and pharmacology and provides a researched and documented method of action for the active ingredients. With special emphasis on the plant’s role in treating high blood pressure, the author looks at medical uses of the plant, critically examining its adverse side effects, toxicology, and carcinogenicity. The author refutes the association between the plant and carcinogenicity and discusses the importance of correct dosing and of screening patients to minimize the occurrence of depression. He concludes with the recommendation of use of low dose Rauwolfia (LDR) for suitable patients with hypertension. The plant provides clinicians with a safe and effective adjunct to pharmaceuticals in the treatment of high blood pressure. PMID:26770146

Cutaneous Adverse Effects of Neurologic Medications.

PubMed

Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

2016-03-01

Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

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

PubMed

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

2014-04-01

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

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

PubMed Central

Aabech, Henning S.; Sundet, Kjetil

2014-01-01

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

Safety of the two-step tuberculin skin test in Indian health care workers.

PubMed

Christopher, Devasahayam J; Shankar, Deepa; Datey, Ashima; Zwerling, Alice; Pai, Madhukar

2014-12-01

Health care workers (HCW) in low and middle income countries are at high risk of nosocomial tuberculosis infection. Periodic screening of health workers for both TB disease and infection can play a critical role in TB infection control. Occupational health programs that implement serial tuberculin skin testing (TST) are advised to use a two-step baseline TST. This helps to ensure that boosting of waned immune response is not mistaken as new TB infection (i.e. conversion). However, there are no data on safety of the two-step TST in the Indian context where HCWs are repeatedly exposed. Nursing students were recruited from 2007 to 2009 at the Christian Medical College and Hospital, Vellore, India. Consenting nursing students were screened with a baseline two-step TST at the time of recruitment. From 2007 to 2008 adverse events were recorded when reported during the TST reading (Cohort A). Nurses recruited in the final study year (2009) answered an investigator administered questionnaire assessing all likely side-effects Cohort B). This information was extracted from the case report forms and analysed. Between 2007 and 09, 800 trainees consented to participate in the annual TB screening study and 779 did not have a past history of TB or recall a positive TST and were selected to administer TST. Of these, 755 returned for reading the result and had complete data and were included for the final analysis - 623 subjects in (cohort A) and 132 in (cohort B). These were included for the final analysis. In cohort A only 1.3% reported adverse events. In cohort B, as per the investigator administered questionnaire; 25% reported minor side effects. Itching and local pain were the most common side effects encountered. There were no major adverse events reported. In particular, the adverse events were similar in the second step of the test and not more severe. Screening of HCWs with two-step TST for LTBI is simple and safe, and hence suitable for wide scale implementation in high-burden settings such as India. Copyright © 2014 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

PubMed

Liu, Xiao; Chen, Hsinchun

2015-12-01

Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. Published by Elsevier Inc.

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

PubMed

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

2015-12-15

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

Are Medications Involved in Vision and Intracranial Pressure Changes Seen in Spaceflight

NASA Technical Reports Server (NTRS)

Wotring, Virginia E.

2015-01-01

The Food and Drug Association Adverse Event Reports (FDA AER) from 2009-2011 were used to create a database from millions of known and suspected medication-related adverse events among the general public. Vision changes, sometimes associated with intracranial pressure changes (VIIP), have been noted in some long duration crewmembers. Changes in vision and blood pressure (which can subsequently affect intracranial pressure) are fairly common side effects of medications. The purpose of this study was to explore the possibility of medication involvement in crew VIIP symptoms.

Discrepancies in the evaluation of the safety of the human papillomavirus vaccine.

PubMed

Cervantes, Jorge L; Doan, Amy Hoanganh

2018-01-01

Despite being more than ten years since its introduction, global acceptance to the human papillomavirus (HPV) vaccine is still low. The immunogenetic background of the host, and HPV antigen recognition, are important in natural HPV infection, and should be taken into account in the understanding of adverse autoimmune reactions by the HPV vaccine in certain groups. There is no doubt of the benefit of vaccines in the reduction of the incidence of infectious diseases, and in the case of HPV, the prevention of persistent infection that would lead to cervical cancer. Side-effects, however, should be closely monitored and reported without any bias, to ensure that the benefits of vaccines outweigh the risks of adverse reactions. In this article we bring the attention on certain adverse effects of the vaccine against HPV that have not been well studied as they are not well defined. We also compare the different approaches on HPV vaccine policies regarding its adverse reactions in countries like Japan and Colombia, vs. the recommendations issued by the WHO.

Statin Therapy: Review of Safety and Potential Side Effects.

PubMed

Ramkumar, Satish; Raghunath, Ajay; Raghunath, Sudhakshini

2016-11-01

Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins. Major trials and review articles on the safety of statins were identified in a search of the MEDLINE database from 1980 to 2016, which was limited to English articles. Myalgia is the most common side effect of statin use, with documented rates from 1-10%. Rhabdomyolysis is the most serious adverse effect from statin use, though it occurs quite rarely (less than 0.1%). The most common risk factors for statin-related myopathy include hypothyroidism, polypharmacy and alcohol abuse. Derangement in liver function tests is common, affecting up to 1% of patients; however, the clinical significance of this is unknown. Some statin drugs are potentially diabetogenic and the risk appears to increase in those patients on higher doses. Pitavastatin has not been associated with increased risk of diabetes. Statins have not been proven to increase the risk of malignancy, dementia, mood disorders or acute interstitial nephritis. However, statins do have multiple drug interactions, primarily those which interact with the cytochrome p450 enzyme group. Overall, statin drugs appear to be safe for use in the vast majority of patients. However, patients with multiple medical co-morbidities are at increased risk of adverse effects from long-term statin use.

Maternal and fetal side effects of tocolysis using transdermal nitroglycerin or intravenous fenoterol combined with magnesium sulfate.

PubMed

Schleussner, Ekkehard; Möller, Arne; Gross, Walter; Kähler, Christiane; Möller, Udo; Richter, Sabine; Seewald, Hans Joachim

2003-01-10

To compare the maternal and fetal side effects of transdermal nitroglycerin and intravenous fenoterol combined with magnesium sulfate in a prospective randomised study. Fifty pregnant women between 27 and 35 weeks of gestation with preterm labour were treated with either nitroglycerin (0.4-0.8 mg/h) or fenoterol (60 - 120 microg/h). Outcome parameters were (1) the effects on fetal and maternal heart frequency (FHF/MHF) and blood pressure, and (2) subjective experiences of adverse effects assessed by utilising a questionnaire. In the fenoterol group, elevated mean MHF, FHF and systolic blood pressure were recorded compared to nitroglycerin. Fewer maternal side effects were reported in the nitroglycerin group. Palpitations (82%), tremor (68%) and restlessness (64%) were most common in the fenoterol group (two drop-outs), whereas nitroglycerin caused headaches in 71% of the cases (four drop-outs). Transdermal nitroglycerin appears to be a safe therapy for the mother and fetus and is a promising new option for the treatment of preterm labour.

Levetiracetam in adult patients with and without learning disability: focus on behavioral adverse effects.

PubMed

Brodtkorb, Eylert; Klees, Theresa M; Nakken, Karl O; Lossius, Rasmus; Johannessen, Svein I

2004-04-01

Optimal antiepileptic drug treatment in patients with learning disability (LD) represents a particular challenge. These patients are often unable to report toxicity, and side effects may manifest as behavioral problems. The aim of this open study was to compare efficacy and tolerability of levetiracetam (LEV) in patients with LD and those without LD. One hundred eighty-four consecutive adult patients who received LEV were followed for an average of 8.1 months. Fifty-six patients (30%) had LD. Thirty-nine percent of patients with refractory epilepsy (37% with and 40% without LD) had > 50% seizure reduction. Significantly more behavioral side effects (23% vs 10%) and a tendency toward less reported somatic central nervous side effects were found in the LD group. We conclude that LEV is equally effective and well tolerated in both patients with LD and patients without LD. However, behavioral problems are more frequent in patients with LD, whereas the tendency toward seizure increase is not enhanced.

Experimental Investigations of the Effects of Underwater Explosions on Swimbladder Fish, II: 1975 Chesapeake Bay Tests

DTIC Science & Technology

1976-09-21

Ranges Environmental Effects of Explosions 20. ABSTRACT (Continue on reverse side It necessary and Identify by block number; The experiment...CHESAPEAKE BAY TESTS The Navy is required to consider the possible adverse environmental effects of its research operations. When such operations involve...the detonation of underwater explosions, one of the environmental factors to be evaluated is the effect of these explosions on nearby marine life

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Evaluation of tamoxifen in persistent or recurrent nonsquamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

PubMed

Bigler, L R; Tate Thigpen, J; Blessing, J A; Fiorica, J; Monk, B J

2004-01-01

This study was undertaken to estimate the antitumor activity of tamoxifen in patients with persistent or recurrent nonsquamous cell carcinoma of the cervix. Furthermore, the nature and degree of adverse effects from tamoxifen in this cohort of individuals was examined. Tamoxifen citrate was to be administered at a dose of 10 mg per orally twice a day until disease progression or unacceptable side effects prevented further therapy. A total of 34 patients (median age: 49 years) were registered to this trial; two were declared ineligible. Thirty-two patients were evaluable for adverse effects and 27 were evaluable for response. There were only six grades 3 and 4 adverse effects reported: leukopenia (in one patient), anemia (in two), emesis (in one), gastrointestinal distress (in one), and neuropathy (in one). The objective response rate was 11.1%, with one complete and two partial responses. In conclusion, tamoxifen appears to have minimal activity in nonsquamous cell carcinoma of the cervix.

Objective Analysis of Poly-L-Lactic Acid Injection Efficacy in Different Settings.

PubMed

Byun, Sang-Young; Seo, Koo-Il; Shin, Jung-Won; Kwon, Soon-Hyo; Park, Mi-Sook; Lee, Joshua; Park, Kyoung-Chan; Na, Jung-Im; Huh, Chang-Hun

2015-12-01

Poly-L-lactic acid (PLLA) filler is known to have continuous volume effect. The objective of this study is to analyze objective volume effect of PLLA in different settings of injection schedule on the cheek. A split-face, evaluator-blind randomized study in 24 volunteers was conducted. One side was injected 3 times with 4 cc dose and the other side was injected 2 times with 6 cc dose per visit. Facial volume loss scale (FVLS) and Vectra were evaluated. Measured average FVLS showed statistically significant improvement both in 3 and 2 times injection sides and maintained efficacy until 12 months. Vectra showed volume difference (cc) between before and after injection. In 3 times injection side, it was increased 2.12 (after 1 month) to 3.17 (after 12 months). In 2 times injection side, it was increased 2.26 (after 1 month) to 3.19 (after 12 months). Gradual volume improvement over 12 months was statistically significant in both sides. There was no statistically significant difference between 3 and 2 times injection in FVLS and Vectra. There was no severe adverse event. Poly-L-lactic acid has continuous volume effect and there was no significant difference by injection times at the same total injection volume.

Pharmacodynamic effects of pilocarpine eye drop enhanced by decreasing its volume of instillation.

PubMed

Lal, A; Kataria, V; Rajpal, A; Khanna, N

1995-07-01

Previous studies have proved that as the volume of the drug solution instilled into the eye is decreased, the fraction of the dose absorbed into the ocular tissue is increased and the adverse drug reactions lowered. The present study investigated the acute effects of different drop volumes (10 microliters, 20 microliters, 40 microliters, and 80 microliters) of pilocarpine nitrate (2%) on pupil diameter, heart rate, and adverse reaction profile, in 12 healthy human volunteers. The drop volumes of 10 microliters and 20 microliters produced more miosis and less side effects than 40 microliters and 80 microliters drop volumes. This may be due to more penetration of the drug into the ocular tissue and less drainage into the nasolacrimal system.

Orofacial and respiratory tardive dyskinesia: potential side effects of 2-dimethylaminoethanol (deanol)?

PubMed

Haug, B A; Holzgraefe, M

1991-01-01

A case of essential tremor since early adultness is presented, which has been treated successfully with the acetylcholine precursor 2-dimethylaminoethanol (deanol) for 10 years. Development of a marked dyskinesia syndrome affecting predominantly orofacial and respiratory musculature has been noticed with this medication. Partial remission after discontinuation and a favorable response to anticholinergics are suggestive of an adverse drug effect.

Household Density and Academic Standing among Community College Students: The Effects of Time Orientation and Spatial Self-Regulation

ERIC Educational Resources Information Center

Campagna, Grace

2012-01-01

The purpose of the study was to develop a multifactorial model tracing paths from housing affordances to academic outcomes in higher education. The study sought to connect two areas of psychological research: on one side, the adverse effects of environmental stressors and inadequate self-regulation upon life course prospects and, on the other, the…

Low-fluence Q-switched Nd: YAG 1064-nm laser and intense pulsed light for the treatment of melasma.

PubMed

Vachiramon, V; Sirithanabadeekul, P; Sahawatwong, S

2015-07-01

Low-fluence Q-switched Nd:YAG 1064 nm laser (LFQS) and intense pulsed light (IPL) have been shown to be effective in the treatment of melasma. LFQS can target deeper pigment, while IPL can target a wide range of cutaneous structures. However, there is limited information on efficacy and side-effects of the combined treatment. To compare the efficacy and safety of combined LFQS and IPL therapy with LFQS monotherapy in the treatment of melasma. Twenty female patients with mixed-type melasma on both cheeks were treated with LFQS on full face for five sessions at 1-week intervals. One side of the face was randomly assigned to receive additional three sessions of IPL treatments at 2-week intervals. Patients were evaluated 12 weeks after the last treatment. Outcome measures include the assessment by colorimeter and calculated as relative lightness index (R*LI), modified Melasma Area and Severity Index (mMASI), patient satisfaction and adverse effects. Eighteen patients completed the study. Both sides of the face showed significant improvement of R*LI and mMASI. A more rapid improvement of R*LI and mMASI was observed on combined side. At the end of treatment, 55% improvement and 37% improvement of R*LI was observed on combined side and monotherapy side respectively. The overall patients' satisfaction was in favour of the combined side. Recurrence occurred on both sides but there was still a significant decrease compared to baseline. No serious side effect was noted. The combination of LFQS and IPL results in faster clearance of melasma and is more effective than LFQS alone for melasma treatment. However, recurrence is still inevitable. © 2014 European Academy of Dermatology and Venereology.

A Public-Private Consortium Advances Cardiac Safety Evaluation: Achievements of the HESI Cardiac Safety Technical Committee

EPA Science Inventory

The evaluation of cardiovascular side-effects is a critical element in the development of all new drugs and chemicals. Cardiac safety issues have been and continue to be a major cause of attrition and withdrawal due to Adverse Drug Reactions (ADRs) in pharmaceutical drug developm...

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

PubMed

Gao, Mengxuan; Sato, Motoshige; Ikegaya, Yuji

2018-01-01

　During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

PubMed

Gao, Mengxuan; Igata, Hideyoshi; Takeuchi, Aoi; Sato, Kaoru; Ikegaya, Yuji

2017-02-01

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Terbinafine: novel formulations that potentiate antifungal activities.

PubMed

Ma, Y; Chen, X; Guan, S

2015-03-01

Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

PubMed

Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

2013-01-01

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Management of statin-intolerant patient.

PubMed

Arca, M; Pigna, G; Favoccia, C

2012-06-01

Large scale clinical trials have undoubtedly demonstrated that statins are effective in reducing cardiovascular events and all-cause mortality in almost all patient populations. Also the short and long-term safety of statin therapy has been well established in the majority of treated patients. Nevertheless, intolerance to statins must be frequently faced in the clinical practice. The most commonly observed adverse effects of statins are muscle symptoms and elevation of hepatic aminotransferase and creatinine kinase (CK) levels. Overall, myalgia (muscle pain with or without plasma CK elevations) and a single abnormally elevated liver function test constitute approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in the patients and are likely to reduce patient's adherence and, consequently, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve knowledge on the clinical aspects of side effects of statins and the ability to manage patients with intolerance to statins. Numerous different approaches to statin-intolerant patients have been suggested, but an evidence-based consensus is difficult to be reached due to the lack of controlled trials. Therefore, it might be useful to review protocols and procedures to control statin intolerance. The first step in managing intolerant patients is to determine whether the adverse events are indeed related to statin therapy. Then, the switching to another statin or lower dosage, the alternate dosing options and the use of non-statin compounds may be practical strategies. However, the cardiovascular benefit of these approaches has not been established, so that their use has to be employed after a careful clinical assessment of each patient.

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

PubMed

Cohen, Jonah; Grunwald, Douglas; Grossberg, Laurie B; Sawhney, Mandeep S

2017-10-01

Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.

Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects

PubMed Central

2017-01-01

BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that typically presents as an annular or oval erythematous patch or blister and subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo biloba leaf extract and vinpocetine are nutritional supplements used to enhance memory in patients with dementia and age-related memory impairment conditions such as Alzheimer’s disease. PURPOSE: To describe a fixed drug eruption in a man who repeatedly developed pruritus and macular erythema on his distal penile shaft after ingesting a natural product containing Ginkgo biloba and vinpocetine. METHODS: The medical literature was retrospectively reviewed using PubMed, searching specifically for the terms cutaneous/skin adverse/side effects, fixed drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous reviews of the subject were critically assessed, and the salient features of cutaneous adverse effects in patients receiving either Ginkgo biloba or vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact dermatitis (following topical exposure) and mucosal symptoms of the mouth and anus (following oral exposure); in addition, an erythematous maculopapular generalized eruption or possibly Steven-Johnson syndrome can occur after oral ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated with vinpocetine ingestion. Pruritus and an annular erythema localized to the distal penile shaft developed after initial and repeat ingestion of a Ginkgo biloba/vinpocetine product. CONCLUSION: Ginkgo biloba and vinpocetine should be added to the agents that can potentially cause a fixed drug eruption. PMID:29344321

Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects.

PubMed

Cohen, Philip R

2017-10-01

BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that typically presents as an annular or oval erythematous patch or blister and subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo biloba leaf extract and vinpocetine are nutritional supplements used to enhance memory in patients with dementia and age-related memory impairment conditions such as Alzheimer's disease. PURPOSE: To describe a fixed drug eruption in a man who repeatedly developed pruritus and macular erythema on his distal penile shaft after ingesting a natural product containing Ginkgo biloba and vinpocetine. METHODS: The medical literature was retrospectively reviewed using PubMed, searching specifically for the terms cutaneous/skin adverse/side effects, fixed drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous reviews of the subject were critically assessed, and the salient features of cutaneous adverse effects in patients receiving either Ginkgo biloba or vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact dermatitis (following topical exposure) and mucosal symptoms of the mouth and anus (following oral exposure); in addition, an erythematous maculopapular generalized eruption or possibly Steven-Johnson syndrome can occur after oral ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated with vinpocetine ingestion. Pruritus and an annular erythema localized to the distal penile shaft developed after initial and repeat ingestion of a Ginkgo biloba/vinpocetine product. CONCLUSION: Ginkgo biloba and vinpocetine should be added to the agents that can potentially cause a fixed drug eruption.

Life-threatening complications of ibogaine: three case reports.

PubMed

Paling, F P; Andrews, L M; Valk, G D; Blom, H J

2012-11-01

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.

Medication errors: the role of the patient.

PubMed

Britten, Nicky

2009-06-01

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

[Antidepressant and tolerance: Determinants and management of major side effects].

PubMed

David, D J; Gourion, D

2016-12-01

Antidepressant therapy aims to reach remission of depressive symptoms while reducing the complications and risks of relapse. Even though they have proven their efficacy, it takes several weeks for antidepressants to demonstrate full effectiveness, and adverse effects occur more quickly or (quicker) which can be a source of poor compliance. This latest aspect often leads to dose reduction and/or change of molecule that have the effect of delaying remission. This review attempts to present, from the pharmacological properties of the major classes of antidepressants (monoamine oxidase inhibitor [MAOI], tricyclic antidepressants [TCA], selective serotonin reuptake inhibitor [SSRI] and serotonin and noradrenaline reuptake inhibitor [SNRI]), to the pharmacological mechanisms involved in adverse effects by focusing on sexual dysfunction, nausea/vomiting, and weight changes and sleep disruption. If the activation of dopamine D 1/2  or norepinephrine receptors through the autonomic nervous system controls and facilitates sexual desire, increasing serotoninergic transmission through 5-HT 1B/2A/2C receptors activation inhibits this process. The pharmacological properties of drugs inducing nausea/vomiting activate opiate receptors μ, increase dopaminergic and serotoninergic transmission activating the dopamine D 2  and serotonin 5-HT 3  receptors, respectively. Among the causes responsible for weight gain under antidepressant therapy, monoamine neurotransmission still plays an important role. The blockade of serotonin 5-HT 2C or histamine H 1  receptors is directly responsible for weight gain. Finally, the activation of 5-HT 1A/1B/3/7 serotoninergique receptors modulates wakefulness, raid eyes movement or sleep duration. In conclusion, if antidepressant activity of SERT or MAO inhibitors is an indirect consequence of postsynaptic 5-HT, DA, NA receptor activation, it is also responsible for side effects, causes of poor compliance and hence therapeutic failures. Finally, we need to take into account the key role of the nocebo effect in the occurrence of adverse effects. The next generation of antidepressant would aim to have a rapid efficacy in patients unresponsive or resistant to drugs currently available while improving certain effects of tolerance through an optimization of their psychopharmacological properties leading to a reduction of their side effects. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[Psychoanalysis and Side Effect].

PubMed

Shirahase, Joichiro

2015-01-01

A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side effect.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients. PMID:16168114

Gold standards in pharmacovigilance: the use of definitive anecdotal reports of adverse drug reactions as pure gold and high-grade ore.

PubMed

Hauben, Manfred; Aronson, Jeffrey K

2007-01-01

Anecdotal reports of adverse drug reactions are generally regarded as being of poor evidential quality. This is especially relevant for postmarketing drug safety surveillance, which relies heavily on spontaneous anecdotal reports. The numerous limitations of spontaneous reports cannot be overemphasised, but there is another side to the story: these datasets also contain anecdotal reports that can be considered to describe definitive adverse reactions, without the need for further formal verification. We have previously defined four categories of such adverse reactions: (i) extracellular or intracellular tissue deposition of the drug or a metabolite; (ii) a specific anatomical location or pattern of injury; (iii) physiological dysfunction or direct tissue damage demonstrable by physicochemical testing; and (iv) infection, as a result of the administration of an infective agent as the therapeutic substance or because of demonstrable contamination. In this article, we discuss the implications of these definitive ('between-the-eyes') adverse effects for pharmacovigilance.

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials.

PubMed

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-08-01

To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain

PubMed Central

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-01-01

Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP. PMID:26505059

Physical Health and Drug Safety in Individuals with Schizophrenia

PubMed Central

Kelly, Martina; Urness, Doug; Teehan, Michael; Ismail, Zahinoor; Gardner, David

2017-01-01

Background: While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. Methods: We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context. Results: Prescribers are encouraged to use the lowest effective dose and to avoid the routine use of multiple antipsychotics. Scheduled monitoring of body mass index, waist circumference, blood pressure, glucose, lipids, prolactin, electrocardiograms, and extrapyramidal symptoms is recommended. Lifestyle interventions are recommended to mitigate antipsychotic-induced weight gain. Prescribers should follow Canadian guidelines on the treatment of obesity, dyslipidemia, and diabetes. Recommendations on antipsychotic drug choice are made for users particularly concerned about extrapyramidal symptoms. Conclusion: Careful monitoring and attention by prescribers may mitigate adverse effects associated with antipsychotic medications. PMID:28718324

Commercial Online Social Network Data and Statin Side-Effect Surveillance: A Pilot Observational Study of Aggregate Mentions on Facebook.

PubMed

Huesch, Marco D

2017-12-01

Surveillance of the safety of prescribed drugs after marketing approval has been secured remains fraught with complications. Formal ascertainment by providers and reporting to adverse-event registries, formal surveys by manufacturers, and mining of electronic medical records are all well-known approaches with varying degrees of difficulty, cost, and success. Novel approaches may be a useful adjunct, especially approaches that mine or sample internet-based methods such as online social networks. A novel commercial software-as-a-service data-mining product supplied by Sysomos from Datasift/Facebook was used to mine all mentions on Facebook of statins and stain-related side effects in the US in the 1-month period 9 January 2017 through 8 February 2017. A total of 4.3% of all 25,700 mentions of statins also mentioned typical stain-related side effects. Multiple methodological weaknesses stymie interpretation of this percentage, which is however not inconsistent with estimates that 5-20% of patients taking statins will experience typical side effects at some time. Future work on pharmacovigilance may be informed by this novel commercial tool, but the inability to mine the full text of a posting poses serious challenges to content categorization.

Human Response to Pyridostigmine Bromide.

DTIC Science & Technology

1984-03-01

Lack of adverse effects other than overdose symptoms, it can be concluded that administration of pyridostigmine to normal subject is prob- abLy safe...neuromuscular transmission. Based on the results of the military studies and the general lack M of side effects other than overdose symptoms cited in the...Bentz, E.W., and StoeLting, R.K., Prolonged Response to Succiny l choline Fol lowing Pancuronium Reversal with Pyridostigmine, Anesthesiology 44, 258

Vibration anesthesia for the reduction of pain with facial dermal filler injections.

PubMed

Mally, Pooja; Czyz, Craig N; Chan, Norman J; Wulc, Allan E

2014-04-01

Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections. The analgesic effect of this method was tested in this study during facial dermal filler injections. The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections. This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds, tear troughs, cheeks, and other facial sites. The injections were administered in a randomly assigned split-face design. One side of the patient's face received vibration together with dermal filler injections, whereas the other side received dermal filler injections alone. The patients completed a posttreatment questionnaire pertaining to injection pain, adverse effects, and preference for vibration with future dermal filler injections. The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections. No adverse events were reported. The majority of the patients (95 %) reported a preference for vibration anesthesia with subsequent dermal filler injections. Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Immunoadsorption or plasma exchange in the treatment of autoimmune encephalitis: a pilot study.

PubMed

Heine, Josephine; Ly, Lam-Thanh; Lieker, Ina; Slowinski, Torsten; Finke, Carsten; Prüss, Harald; Harms, Lutz

2016-12-01

Therapeutic apheresis has emerged as a major treatment option for autoantibody-associated inflammatory diseases of the nervous system. This includes patients with autoimmune encephalitides caused by antibodies against neuronal proteins. Plasma exchange (PE) and immunoadsorption (IA) constitute two possibilities to eliminate pathogenic antibodies from patients' plasma, but their efficacy and safety has not been prospectively assessed in larger patient groups of autoimmune encephalitides. In a prospective observational case control study, we, therefore, investigated the disease courses and treatment effects of 21 patients with autoimmune encephalitis associated with NMDAR, LGI1, CASPR2, GAD, mGluR5 and Hu antibodies. Patients were randomly assigned to receive PE (n = 11) or IA (n = 10). Symptoms were evaluated using the modified Rankin Scale (mRS). Side effects or adverse events were recorded. Both interventions, IA (p = 0.014) and PE (p = 0.01), resulted in significant reduction of the median mRS. With IA, 60 % of the patients improved clinically by at least 1 mRS score, none worsened. PE led to a comparable symptom reduction in 67 % of the cases. During 83 PE sessions, three adverse events were documented, while no side effects occurred under IA. Symptom improvement was significantly associated with younger age (r = -0.58), but not with disease duration. Therapeutic apheresis was most effective for neuronal surface antigens (83.3 %), followed by intracellular-synaptic antigens (66.7 %). Both IA and PE resulted in moderate to marked clinical improvement, with a low rate of adverse events. Apheresis is well tolerated and effective also as first-line therapy in autoimmune encephalitis, particularly in patients with antibodies targeting neuronal surfaces.

Zhibitai and low-dose atorvastatin reduce blood lipids and inflammation in patients with coronary artery disease.

PubMed

Zhao, Yuhong; Peng, Ran; Zhao, Wang; Liu, Qiong; Guo, Yuan; Zhao, Shuiping; Xu, Danyan

2017-02-01

Atorvastatin decreases blood lipids but is associated with side effects. Zhibitai is a traditional Chinese medicine used to treat blood lipid disorders. The objective of this study is to evaluate the lipid-lowering effect, antiinflammatory effect, and adverse events of zhibitai combined to atorvastatin in patients with coronary heart diseases (CHDs). Patients with CHD (n = 150) were randomized to: zhibitai 480 mg + atorvastatin 10 mg (ZA10 group), atorvastatin 20 mg (A20 group), and atorvastatin 40 mg (A40 group). Lipid profile, cardiotrophin-1 (CT-1), and C-reactive protein (CRP) were measured after 4 and 8 weeks of treatment. Self-reported side effects, liver function, kidney function, and creatine kinase levels were monitored. After 8 weeks, triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B100 (ApoB100) levels were decreased in the ZA10 group (-64%, -37%, -46%, and -54%, respectively, compared with baseline), and these changes were similar to those of the A40 group (P > 0.05). CT-1 and high sensitivity-C reactive protein (hs-CRP) levels were significantly decreased in the ZA10 group after 4 and 8 weeks (4 weeks: -73% and 96%; 8 weeks: -89% and -98%; all P < 0.01), without differences among the 3 groups (P > 0.05). After 8 weeks of treatment, adverse events (abdominal distention, nausea, vomiting, and hunger) were found in 4, 5, and 7 patients in the ZA10, A20, and A40 groups, respectively. ZA10 significantly reduced triglycerides, TC, LDL-C, ApoB, CT-1, and hs-CRP levels in patients with CHD, similar to the effects of A40 and A20, but ZA10 lead to fewer adverse events.

Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08).

PubMed

Templeton, Arnoud J; Ribi, Karin; Surber, Christian; Sun, Hong; Hsu Schmitz, Shu-Fang; Beyeler, Michael; Dietrich, Daniel; Borner, Markus; Winkler, Annette; Müller, Andreas; von Rohr, Lukas; Winterhalder, Ralph C; Rochlitz, Christoph; von Moos, Roger; Zaman, Khalil; Thürlimann, Beat J K; Ruhstaller, Thomas

2014-06-01

Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

SSRI adverse events: how to monitor and manage.

PubMed

Murphy, Tanya K; Segarra, Ana; Storch, Eric A; Goodman, Wayne K

2008-04-01

Antidepressants are efficacious for pediatric major depressive disorder, obsessive compulsive disorder (OCD), and non-OCD anxiety disorders. Antidepressants should be used in an evidence-based fashion, with frequent monitoring for side effects, especially when initiating treatment and adjusting dosage. With diligence to appropriate prescribing and monitoring, the benefits of therapy outweigh the potential of treatment related risk.

Contents of Japanese pro- and anti-HPV vaccination websites: A text mining analysis.

PubMed

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2018-03-01

In Japan, the human papillomavirus (HPV) vaccination rate has sharply fallen to nearly 0% due to sensational media reports of adverse events. Online anti-HPV-vaccination activists often warn readers of the vaccine's dangers. Here, we aimed to examine frequently appearing contents on pro- and anti-HPV vaccination websites. We conducted online searches via two major search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as "pro," "anti," or "neutral" according to their claims, with the author(s) classified as "health professionals," "mass media," or "laypersons." We then conducted a text mining analysis. Of the 270 sites analyzed, 16 contents were identified. The most frequently appearing contents on pro websites were vaccine side effects, preventable effect of vaccination, and cause of cervical cancer. The most frequently appearing contents on anti websites were vaccine side effects, vaccine toxicity, and girls who suffer from vaccine side effects. Main disseminators of each content according to the author's expertise were also revealed. Pro-HPV vaccination websites should supplement deficient contents and respond to frequent contents on anti-HPV websites. Effective tactics are needed to better communicate susceptibility to cervical cancer, frequency of side effects, and responses to vaccine toxicity and conspiracy theories. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Hematopoietic Growth Factor in the Management of Hematological Side Effects Associated to Antiviral Treatment for Hcv Hepatitis

PubMed Central

Mancino, Paola; Falasca, Katia; Ucciferri, Claudio; Pizzigallo, Eligio; Vecchiet, Jacopo

2010-01-01

Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection. PMID:21415945

Infant titi monkey behavior in the open field test and the effect of early adversity

PubMed Central

Larke, Rebecca H.; Toubiana, Alice; Lindsay, Katrina A.; Mendoza, Sally P.; Bales, Karen L.

2017-01-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. PMID:28605039

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne.

PubMed

Almond-Roesler, B; Blume-Peytavi, U; Bisson, S; Krahn, M; Rohloff, E; Orfanos, C E

1998-01-01

Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo-isotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.

Comparative study of buffered 50% glycolic acid (pH 3.0) + 0.5% salicylic acid solution vs Jessner's solution in patients with acne vulgaris.

PubMed

In Jae, Jeong; Dong Ju, Hyun; Dong Hyun, Kim; Yoon, Moon Soo; Lee, Hee Jung

2017-11-21

Superficial chemical peels are frequently used in acne vulgaris treatment. Although glycolic acid (GA) has been widely used in clinical practice, its pH ranges from 0.08-2.75 and thus should be neutralized after application to avoid burns. To evaluate treatment efficacy and safety of chemical peeling using buffered 50% GA (pH 3.0) + 0.5% salicylic acid (SA) solution that does not need to be neutralized in the treatment of acne vulgaris compared to the conventional peeling using Jessner's solution. We performed a prospective, randomized, evaluator-blind, split-face clinical trial. Twenty patients were randomized by assigning one side of each patient's face to receive a 50% GA (pH 3.0) + 0.5% SA peel (GA side) and the other side to receive the Jessner's solution (Jessner's solution side). All patients underwent 2 sessions of treatment spaced 2 weeks apart. Lesion count, acne severity, subjective efficacy assessment, and side effects were evaluated. The total lesion count was significantly reduced for the GA and Jessner's solution sides (P < .001). However, there was no significant difference in the total lesion count, acne severity, or subjective efficacy assessment between the 2 sides (P > .05). The GA side had fewer side effects than the Jessner's solution side. The results of this study suggest that chemical peeling using the 50% GA (pH 3.0) + 0.5% SA solution can be as effective and convenient as the conventional peeling using Jessner's solution in the treatment of acne vulgaris and may show fewer adverse events than the conventional peeling. © 2017 Wiley Periodicals, Inc.

Warfarin-induced Venous Limb Gangrene

PubMed Central

Grim Hostetler, Sarah; Sopkovich, Jennifer; Dean, Steven

2012-01-01

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene. PMID:23198012

Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

PubMed

Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

2016-07-01

To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

Patient Experience of Symptoms and Side Effects when Treated with Osimertinib for Advanced Non-Small-Cell Lung Cancer: A Qualitative Interview Substudy.

PubMed

Rydén, Anna; Blackhall, Fiona; Kim, Hye Ryun; Pillai, Rathi N; Braam, Lauren; Martin, Mona L; Walding, Andrew

2017-10-01

Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients receiving the drug.

Tolazoline reversal of xylazine in bison (Bison bison): Mitigation of adverse effects

USGS Publications Warehouse

Roffe, Thomas J.; Sweeney, Steven J.; Williams, Beth; Quist, Charlotte

2002-01-01

Tolazoline is a mixed alpha-1 and -2 adrenergic antagonist used to reverse the sedative, analgesic and muscle-relaxing effects of xylazine, a potent alpha adrenergic agonist. Tolazoline has been used in cattle and is superior to yohimbine, another alpha adrenergic antagonist, in this species. In white-tailed deer, tolazoline shortened recovery times and reversed xylazine-induced bradycardia, respiratory depression, and bloat following xylazine-ketamine anesthesia (Kreeger et al. 1986). We have used it for a number of years in moose without any detected adverse reactions. Caulkett et al. (2000) used tolazoline in wood bison to reverse the xylazine-induced effects of xylazine-tiletamine/zolazepam anesthesia and did not report any ill effects. However, the reported side effects of tolazoline in horses (species for which the drug was developed and is labeled) include abdominal discomfort, gastrointestinal hypermotility, diarrhea, tachycardia, ventricular dysrhythmia, hypertension and apprehensiveness.

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.

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: A randomized controlled trial

PubMed Central

Beaulieu, André D; Peloso, Paul M; Haraoui, Boulos; Bensen, William; Thomson, Glen; Wade, John; Quigley, Patricia; Eisenhoffer, John; Harsanyi, Zoltan; Darke, Andrew C

2008-01-01

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two-to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration. PMID:18443672

Hydroxyurea-induced oral ulceration.

PubMed

Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin

2015-12-01

Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Does Googling lead to statin intolerance?

PubMed

Khan, Sarah; Holbrook, Anne; Shah, Baiju R

2018-07-01

The nocebo effect, where patients with expectations of adverse effects are more likely to experience them, may contribute to the high rate of statin intolerance found in observational studies. Information that patients read on the internet may be a precipitant of this effect. The objective of the study was to establish whether the number of websites about statin side effects found using Google is associated with the prevalence of statin intolerance. The prevalence of statin intolerance in 13 countries across 5 continents was established in a recent study via a web-based survey of primary care physicians and specialists. Using the Google search engine for each country, the number of websites about statin side effects was determined, and standardized to the number of websites about statins overall. Searches were restricted to pages in the native language, and were conducted after connecting to each country using a virtual private network (VPN). English-speaking countries (Australia, Canada, UK, USA) had the highest prevalence of statin intolerance and also had the largest standardized number of websites about statin side effects. The sample Pearson correlation coefficient between these two variables was 0.868. Countries where patients using Google are more likely to find websites about statin side effects have greater levels of statin intolerance. The nocebo effect driven by online information may be contributing to statin intolerance. Copyright © 2018 Elsevier B.V. All rights reserved.

[Prevalence of hyperimmunization against tetanus and systematic adverse reactions to tetanus toxoid in children].

PubMed

Szenborn, Leszek; Saraczyńska, Elzbieta; Ilnicki, Lucjan

2008-01-01

during the last 30 years we have observed only two children (aged 6 and 3 years) with systemic reactions after tetanus vaccine, given unnecessarily 5 and 10 months after appropriate primary immunization. The adverse reactions after tetanic toxoid appear to be directly related to excessive titre of protecting antibodies. The aim of this paper is to investigate the concentration of tetanus antibodies, which may help to define the risk of adverse reactions. tests were carried out in 190 children (86 male, 104 female) aged 7 (n=95) and 14 (n=95) years. Antibodies to tetanus toxoid were determined using a commercial EIA. all examined children had protective concentration of tetanus antibodies (above 0.01 IU/ml; range from 0.1 to 6.0 IU/mL). There were significant differences between antibodies concentrations (GMC) in children aged 7 and 14 years (0.93 vs. 1,76 IU/ml; p=0.048). The antibodies concentrations above 1 IU/ml which indicate long term protection were more frequently observed in children aged 14 than those aged 7 years (73 vs. 59%; not statistically significant). Only 6.84% of all examined children (n=190) had high antibodies concentration above 5 IU/ml, which could increase the risk of side effects if the next booster would be given during the next 5 years. children in Poland are only slightly exposed to risk of severe side effects after vaccination against tetanus. The tetanus immunity in examined children can be assessed as very good.

Oral adverse effects due to the use of Nevirapine.

PubMed

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

2008-01-01

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

General equilibrium effects of a supply side GHG mitigation option under the Clean Development Mechanism.

PubMed

Timilsina, Govinda R; Shrestha, Ram M

2006-09-01

The Clean Development Mechanism (CDM) under the Kyoto Protocol to the United Nations Framework Convention on Climate Change is considered a key instrument to encourage developing countries' participation in the mitigation of global climate change. Reduction of greenhouse gas (GHG) emissions through the energy supply and demand side activities are the main options to be implemented under the CDM. This paper analyses the general equilibrium effects of a supply side GHG mitigation option-the substitution of thermal power with hydropower--in Thailand under the CDM. A static multi-sector general equilibrium model has been developed for the purpose of this study. The key finding of the study is that the substitution of electricity generation from thermal power plants with that from hydropower plants would increase economic welfare in Thailand. The supply side option would, however, adversely affect the gross domestic product (GDP) and the trade balance. The percentage changes in economic welfare, GDP and trade balance increase with the level of substitution and the price of certified emission reduction (CER) units.

Knowledge and perceptions of the risks of non-steroidal anti-inflammatory drugs among orthopaedic patients in Thailand.

PubMed

Phueanpinit, Pacharaporn; Pongwecharak, Juraporn; Krska, Janet; Jarernsiripornkul, Narumol

2016-10-01

Background There is a high incidence of adverse effects from non-steroidal antiinflammatory drugs (NSAIDs) in Thailand, but patients' perceptions and knowledge of NSAID risks is unknown. Objective This study aims to assess patients' perceptions and knowledge of NSAID risks and factors affecting them. Setting University hospital in North-East of Thailand. Method A Cross-sectional study conducted over 4 months, using a self-administered questionnaire. Patients prescribed NSAIDs for at least one month duration from orthopaedic clinic were recruited using systematic random sampling. Main outcome measure Patients' perceptions on NSAID risks, knowledge on risk factors, and their associated factors. Results A total of 474 questionnaires were assessed. Overall perceptions of risks was low (scoring below five on a 0-10 visual analogue scale), with risks associated with the renal system scoring highest. Perceived risk of gastrointestinal problems differed between patients using non-selective and selective NSAIDs (3.47 ± 2.75 vs 2.06 ± 2.98; P < 0.001). Receiving side effect information from a health professional was associated with higher risk perception. Most patients (80 %) identified high doses, renal disease and gastrointestinal ulcer increased risks of NSAIDs, but fewer than half recognized that use in the elderly, multiple NSAID use, drinking, hypertension and cardiovascular disease also increased risk of adverse events. Having underlying diseases and receiving side effect information were associated with 1.6-2.0 fold increased knowledge of NSAID risks. Conclusion Perceptions and knowledge concerning NSAID risks was generally low in Thai patients, but higher in those who had received side effect information. Risk-related information should be widely provided, especially in high-risk patients.

Alternative Therapies for Diabetes: A Comparison of Western and Traditional Chinese Medicine (TCM) Approaches.

PubMed

Xiao, Eric; Luo, Luguang

2017-05-18

Across the world, the economic and health costs of diabetes are rising at an alarming rate. Each year in the United States, billions of dollars are spent on T2 Diabetes mellitus (T2DM) treatments, but such treatments are not always effective and can lead to adverse events. Many pharmacological treatments exist to control the primary and secondary symptoms of T2DM, but these medications are not always efficacious, do little to treat secondary T2DM symptoms, and often carry adverse side effects. Traditional Chinese Medicine (TCM) is a form of alternative medicine that is becoming appealing to western healthcare systems because of its comprehensive, holistic approach to managing T2DM patients. Works across TCM printed texts, clinical trial databases, medical association practice guidelines, and the existing literature on TCM and western diabetes treatments (in print and online) are reviewed. Conventional pharmaceutical therapies for T2DM are not efficacious enough to maintain satisfactory blood glucose levels for all patients, and even patients who maintain stable blood glucose levels may still suffer from secondary T2DM symptoms as well as from the side effects of their medications. TCM therapies have demonstrated promising results in T2DM clinical studies without causing the types of side effects associated with standard pharmaceutical treatments. In addition, the economic burden of TCM diabetes treatments on patients and payers is oftentimes less than that of pharmaceutical regimens. TCM approaches can be a viable alternative approach to treatment in the modern U.S. healthcare landscape, but a number of obstacles impede its assimilation into western health systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A randomized, controlled multicentric study of inhaled budesonide and intravenous methylprednisolone in the treatment on acute exacerbation of chronic obstructive pulmonary disease.

PubMed

Ding, Zhen; Li, Xiu; Lu, Youjin; Rong, Guangsheng; Yang, Ruiqing; Zhang, Ruixia; Wang, Guiqin; Wei, Xiqiang; Ye, Yongqing; Qian, Zhaoxia; Liu, Hongyan; Zhu, Daifeng; Zhou, Ruiqing; Zhu, Kun; Ni, Rongping; Xia, Kui; Luo, Nan; Pei, Cong

2016-12-01

Almost all international guidelines recommend corticosteroids for management of exacerbations of chronic obstructive pulmonary disease (COPD), because it leads to improved outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects, there are still concerns regarding the use of systemic corticosteroid (SC). Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing the risk of occurrence of side effects. To measure the clinical efficacy and side effects of nebulized budesonide and systemic methylprednisolone in AECOPD. Valid data from 410 AECOPD patients in 10 hospitals was collected. Patients were randomly divided into 2 groups; budesonide group, treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone group, treated with intravenously injected methylprednisolone (40 mg/day). COPD assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse effects, fasting blood glucose, serum creatinine, alanine aminotransferase levels, and blood drug were measured and analyzed in both groups. Symptoms, pulmonary function and arterial blood gas analysis were significantly improved after treatment in both groups (P < 0.05), with no significant differences between them (P > 0.05), while incidence of adverse events in the budesonide group was lower (P < 0.05). No significant differences in CAT score, days of admission, blood gas analysis results and physiological and biochemical indexes were found between the two groups. Patients treated with methylprednisolone showed a higher degree of PaO 2 level improvement. Results show that inhalation of budesonide (2 mg 3 times/day) and systemic methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In conclusion, inhaled budesonide is an alternative to systemic corticosteroids in AECOPD treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

PubMed

Becker, G M; Gandolfi, A J; Nagle, R B

1987-05-01

Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

Black hairy tongue associated with olanzapine treatment: a case report.

PubMed

Tamam, Lut; Annagur, Bilge Burcak

2006-10-01

Olanzapine is an atypical antipsychotic drug approved for acute and long-term treatment of bipolar disorder. Although relatively safe as compared to other classical antipsychotic medications, there are a number of uncommon adverse effects of olanzapine such as oral cavity lesions. In addition to the relatively common side effect of dry mouth, several articles have reported an association between olanzapine treatment and the development of oral lesions such as apthous stomatitis, pharyngitis, glossitis and oral ulceration. Although there are several cases in which the tongue was affected in conjunction with stomatitis or pharyngitis, we could not find a case report indicating a direct relationship between olanzapine use and a tongue lesion. We present here the case of a patient with bipolar disorder, who developed recurrent black hairy tongue on two different occasions following the addition of olanzapine to lithium treatment. In the present case, xerostomia (dry mouth), which is an adverse reaction of both olanzapine and lithium, may have played a role in the development of black hairy tongue. All agents with a possible side effect of xerostomia may predispose patients to black hairy tongue, especially when they are administered in combination. To preclude the development of this complication with such drugs, extra time and effort should be given to improving oral hygiene.

Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness.

PubMed

Jacobs, W; Das, E; Schagen, S B

2017-01-01

Information about treatment side effects can increase their occurrence; breast cancer (BC) patients showed increased cognitive problem reporting (CPR) and decreased memory performance after information about cognitive side effects. The current study extends previous research on adverse information effects (AIE) by investigating (a) risk factors, (b) underlying mechanisms and (c) an intervention to reduce AIE. In an online experiment, 175 female BC patients were randomly assigned to one of three conditions. In the two experimental groups, patients were informed about the possible occurrence of cognitive problems after chemotherapy with (intervention group) or without (experimental group) reassuring information that 'there are still patients who score well on memory tests'. In the control group, no reference to chemotherapy-related cognitive problems was made. Main dependent measure was CPR. Four moderating and five mediating processes were examined. CPR increased with higher levels of stigma consciousness in the two experimental groups, but not in the no-information control group. Merely informing patients about cognitive side effects may increase their occurrence, especially among individuals vulnerable to patient stereotypes. Adding reassuring information is not sufficient to reduce AIE.

A review and assessment of drug-induced parotitis.

PubMed

Brooks, Krista G; Thompson, Dennis F

2012-12-01

To review the current literature on drug-induced parotitis. Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other drugs have been implicated in the development of parotitis; however, the evidence supporting this association is insufficient to determine causality at this time.

Dabigatran for anticoagulation in atrial fibrillation - early clinical experience in a hospital population and comparison to trial data.

PubMed

Michel, Jonathan; Mundell, David; Boga, Tau; Sasse, Alexander

2013-01-01

Dabigatran is a recently introduced direct thrombin inhibitor licensed for use as an oral anticoagulant for stroke prevention in non-valvular atrial fibrillation. Our prospective observational study aimed to assess the adverse effects, tolerability and patient satisfaction of dabigatran therapy in a hospital-practice population. Patients starting dabigatran, after its release in June 2011, were identified from clinical practice at two Wellington hospitals, New Zealand. Baseline characteristics were recorded from the clinical record and a telephone interview was performed in January 2012. Primary outcomes included adverse events, adherence, and satisfaction with treatment. Data were available for 70 patients: median age 71.9 years (IQR 62.7-79.0), weight 80 kg (IQR 71-95), CHA(2)DS(2)-VASc score 3 (IQR 2-4). Seventy-one percent of patients reported adverse events although the majority were minor. Twenty-four percent (16/70) had discontinued treatment with dabigatran; four due to predominantly gastrointestinal side effects, three due to bleeding (one severe), one as a result of adverse media coverage with the remainder comprising planned treatment discontinuation and undetermined. In total, 29% reported bleeding events, predominantly minor bleeding and bruising. There were no cerebrovascular events. Nineteen percent reported some difficulty with twice daily dosing adherence with 13 of 70 reporting missed doses. Seventy-seven percent reported treatment satisfaction and 79% of those previously treated with warfarin preferred dabigatran. In this population our study demonstrates a discontinuation rate of 10% due to side effects of dabigatran, similar to the rate reported in RE-LY. The majority of patients are satisfied with their treatment and preferred dabigatran to warfarin, mainly due to the reduced requirement for blood testing. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

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...

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.

A survey on the knowledge, beliefs and behaviour of a general adult population in Malaysia with respect to the adverse effects of medicines.

PubMed

Jose, Jimmy; Chong, David; Lynn, Tay Szu; Jye, Goh Ee; Jimmy, Beena

2011-08-01

The aim of the study was to explore, in the Malaysian general population: knowledge and beliefs of the characteristics in general of medication-related side effects and side effects associated with different types of medicines; behaviour related to the safe use of drugs before and after taking a medication; and behaviour in the event of a medication-related side effect. A 24-item self-administered questionnaire was developed and used to survey the general public living or working in suburban Kuala Lumpur, Malaysia. Eight hundred questionnaires were distributed, face to face, by researchers using quota sampling. Respondents' knowledge, belief and behaviour were analysed and correlated with demographics, medical history and experience of side effects. Six hundred and ten respondents completed the questionnaire giving a response rate of 76.3%. The mean knowledge score for the respondents was 18.4±3.6 out of the maximum possible score of 26. Educational level and experience of side effect had an influence on the knowledge score obtained. Respondents had misconceptions regarding the safety of complementary and alternative medicines (CAMs) and over-the-counter medications. Medication history and previous experience with side effects had a significant influence on the higher behaviour score obtained. The survey has shown moderate results with regard to the knowledge of public regarding safety of medications, and there was evidence of under-estimating the risk of medications, especially CAMs. The misconceptions among the public, and inappropriate behaviour on drug safety-related aspects, is a concern which needs to be addressed in the interventions designed. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

Efficacy and Safety of SSRIs, SNRIs, and Placebo in Common Psychiatric Disorders: A Comprehensive Meta-Analysis in Children and Adolescents

PubMed Central

Locher, Cosima; Koechlin, Helen; Zion, Sean R; Werner, Christoph; Pine, Daniel S.; Kirsch, Irving; Kessler, Ronald C.; Kossowsky, Joe

2017-01-01

Importance Depressive disorders (DD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of SSRIs, SNRIs and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, Embase, PsycINFO, Web of Science, and Cochrane through August 2016. Study Selection Published and unpublished randomized, double-blind, placebo-controlled studies of SSRIs or SNRIs in youths diagnosed with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (e.g. tricyclic antidepressants, MAOIs) were excluded. Data Extraction and Synthesis Effect sizes, (ES) calculated as standardized mean differences (Hedges’g) and Risk Ratios (RR) for adverse events, were assessed in a random-effects model. Main Outcome(s) and Measure(s) Primary outcomes, as defined by authors on pre- and post-intervention data, mean change data, and side effect data, were extracted independently by multiple observers following PRISMA guidelines. Results We deemed 36 studies eligible, including 6778 participants; 17 studies for DD, 10 for AD, 8 for OCD and one for PTSD., SSRIs and SNRIs were significantly more effective compared to placebo, yielding a small effect size (g=0.32, p<.001). AD (g=0.56, p<.001) showed significantly larger between-group ES than DD (g=0.20, p<.001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g=1.57, p<.001) compared to those with AD (g=1.03, p<.001). Of note is the relatively large effect size for SSRIs for anxiety disorders g=0.71, p<.001. Compared to placebo, patients taking an antidepressant reported significantly more treatment emergent adverse events (RR=1.07, p=.001 or RR=1.49, p<.001, depending on the reporting method), serious adverse events (RR=1.76, p<.001) and study discontinuation due to side effects (RR=1.79, p<.001). Conclusion and Relevance SSRIs and SNRIs are more effective than placebo, however, the effect is small and disorder-specific, yielding a larger effect for AD than for other conditions. Response to placebo is large, especially in DD. Serious adverse events are significantly more common in SSRIs and SNRIs than placebo. PMID:28854296

Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

PubMed

Shin, Hee Soon; Shon, Dong-Hwa

2015-01-01

An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders.

The effect of an apparent change to a branded or generic medication on drug effectiveness and side effects.

PubMed

Faasse, Kate; Cundy, Tim; Gamble, Greg; Petrie, Keith J

2013-01-01

Generic medications are associated with reduced perceived effectiveness, increased perceived adverse effects, and increased rates of nonadherence compared with brand-name medications. This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects. Sixty-two university students participated in a study purportedly testing the effectiveness of fast-acting β-blocker medications in reducing preexamination anxiety. All tablets were placebos. In session 1, all participants received a yellow tablet ("Betaprol"). In session 2, participants were randomly allocated to receive Betaprol (no change condition) or a white tablet labeled either as "Novaprol" (branded change condition) or "Generic" (generic change condition). Blood pressure and state anxiety were measured before and after tablet ingestion. Side effects attributed to medication were assessed. The no change group showed significantly greater decreases in systolic blood pressure (mean [M] [standard deviation] = -7.72 mm Hg, standard error [SE] = 1.45) than the branded change (M = -2.75 mm Hg, SE = 1.44, p = .02) and generic change (M = -3.26 mm Hg, SE = 1.45, p = .03) groups. The no-change group showed significantly greater decreases in state anxiety (M = -1.53, SE = 0.33) than the branded change (M = -0.50, SE = 0.33, p = .03) and generic change (M = -0.52, SE = 0.33, p = .04) groups. Significantly more side effects were attributed to the medication in the generic change (M = 1.83, SE = 0.23) (but not the branded change) condition when compared with the no change condition (M = 0.87, SE = 0.31, p = .03). Medication formulation change, particularly to generic medication, seems to be associated with reduced subjective and objective measures of medication effectiveness and increased side effects.

Anaesthetics and analgesics; neurocognitive effects, organ protection and cancer reoccurrence an update.

PubMed

Sellbrant, I; Brattwall, M; Jildenstål, P; Warren-Stomberg, M; Forsberg, S; Jakobsson, J G

2016-10-01

Available general and local anaesthetics, third generation inhaled anaesthetics, propofol and amide class local anaesthetics are effective and reassuringly safe. They are all associated to low incidence of toxicology and or adverse-effects. There is however a debate whether anaesthetic drug and technique could exhibit effects beyond the primary effects; fully reversible depression of the central nervous system, dose dependent anaesthesia. Anaesthetics may be involved in the progression of neurocognitive side effects seen especially in the elderly after major surgery, so called Postoperative Cognitive Dysfunction. On the other hand anaesthetics may exhibit organ protective potential, reducing ischemia reperfusion injury and improving survival after cardiac surgery. Anaesthetics and anaesthetic technique may also have effects of cancer reoccurrence and risk for metastasis. The present paper provides an update around the evidence base around anaesthesia potential contributing effect on the occurrence of postoperative cognitive adverse-effects, organ protective properties and influence on cancer re-occurrence/metastasis. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Classics in Chemical Neuroscience: Aripiprazole.

PubMed

Casey, Austen B; Canal, Clinton E

2017-06-21

Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D 2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D 2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D 2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D 2 receptor binding kinetics, have significantly lower risk of movement side effects but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D 2 and D 3 and serotonin 5-HT 1A receptors, as well as antagonist activity at serotonin 5-HT 2A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole's neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.

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.

Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

PubMed

El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

2011-09-01

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

Changes in behavior as side effects in methylphenidate treatment: review of the literature.

PubMed

Konrad-Bindl, Doris Susanne; Gresser, Ursula; Richartz, Barbara Maria

2016-01-01

Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes in the pediatric, adolescent, and adult populations. We conducted a literature search in PubMed, Medline, and Google using the keywords "methylphenidate", "behavioral changes", "adverse effects", and "side effects". A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis. Five studies specifically set out to study, record, and discuss changes in behavior. Eight studies did not set out to study behavioral effects, but record and discuss them. A total of 28 studies recorded behavioral effects, but failed to discuss these further. Three studies did not include behavioral effects. This review records what data have been published in respect of changes in behavior in association with the use of methylphenidate. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of methylphenidate taking.

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.

Captopril in hypertension after renal transplantation.

PubMed Central

Chan, M. K.; Sweny, P.; El Nahas, A. M.; Farrington, K.; Fernando, O. N.; Moorhead, J. F.

1984-01-01

Eight hypertensive renal allograft recipients who had received captopril are presented. Captopril in a maximal daily dose of 250 mg enabled the withdrawal of large doses of beta-blocking agents and vasodilators. Blood pressure was satisfactorily controlled in all except one. No adverse side effects were observed other than the 'first dose' effect which resulted in transient anuria in one patient. Captopril appears to be a useful agent in the management of severe hypertension after renal transplantation. PMID:6369287

Algorithms for Zonal Methods and Development of Three Dimensional Mesh Generation Procedures.

DTIC Science & Technology

1984-02-01

a r-re complete set of equations is used, but their effect is imposed by means of a right hand side forcing function, not by means of a zonal boundary...modifications of flow-simulation algorithms The explicit finite-difference code of Magnus and are discussed. Computational tests in two dimensions...used to simplify the task of grid generation without an adverse achieve computational efficiency. More recently, effect on flow-field algorithms and

Endomorphin derivatives with improved pharmacological properties.

PubMed

Varamini, Pegah; Blanchfield, Joanne T; Toth, Istvan

2013-01-01

Centrally acting opioids, such as morphine, are the most frequently used analgesic agents for the treatment of severe pain. However, their usefulness is limited by the production of a range of adverse effects such as constipation, respiratory depression, tolerance and physical dependence. In addition, opioids generally exhibit poor efficacy against neuropathic pain. Endomorphin-1 and -2, two endogenous opioid peptides, have been shown to produce potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, native endomorphins are poorly suited to clinical applications without modifications. Like all small peptides, endomorphins suffer from poor metabolic stability and a relative inability to penetrate the gastro-intestinal mucosa and blood-brain-barrier. Since the discovery of endomorphins in 1997, a huge number of endomorphin analogs have been designed and synthesized with the aim of developing compounds with improved barrier penetration and resistance to enzymatic degradation. In this review we describe various strategies that have been adopted so far to conquer the major drawbacks associated with endomorphins. They include chemical modifications to produce locally or globally-restricted peptide analogs in addition to application of peptidase inhibitors, which is of minor importance compared to the former strategy. Diverse approaches that resulted in the design and synthesis of pharmacologically active endomorphin analogs with less adverse effects are also discussed giving an insight into the development of opioid peptides with an improved side effect profile.

Safety and effectiveness of cantharidin-podophylotoxin-salicylic acid in the treatment of recalcitrant plantar warts.

PubMed

López López, Daniel; Vilar Fernández, Juan Manuel; Losa Iglesias, Marta Elena; Álvarez Castro, Carlos; Romero Morales, Carlos; García Sánchez, María Matilde; Becerro de Bengoa Vallejo, Ricardo

2016-07-01

The aim of our study was to evaluate the efficacy and safety of topical cantharidin-podophylotoxin-salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013. A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow-up visit or telephone call after treatment and were included in this study. Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty-four patients required one application to eliminate the wart and 21 patients required two applications/patient. Seventy-seven percent of patients experienced blistering - an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding. All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment. © 2016 Wiley Periodicals, Inc.

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.

Distal end side-to-side anastomoses of sequential vein graft to small target coronary arteries improve intraoperative graft flow

PubMed Central

2014-01-01

Background End-to-side anastomoses to connect the distal end of the great saphenous vein (GSV) to small target coronary arteries are commonly performed in sequential coronary artery bypass grafting (CABG). However, the oversize diameter ratio between the GSV and small target vessels at end-to-side anastomoses might induce adverse hemodynamic condition. The purpose of this study was to describe a distal end side-to-side anastomosis technique and retrospectively compare the effect of distal end side-to-side versus end-to-side anastomosis on graft flow characteristics. Methods We performed side-to-side anastomoses to connect the distal end of the GSV to small target vessels on 30 patients undergoing off-pump sequential CABG in our hospital between October 2012 and July 2013. Among the 30 patients, end-to-side anastomoses at the distal end of the GSV were initially performed on 14 patients; however, due to poor graft flow, those anastomoses were revised into side-to-side anastomoses. We retrospectively compared the intraoperative graft flow characteristics of the end-to-side versus side-to-side anastomoses in the 14 patients. The patient outcomes were also evaluated. Results We found that the side-to-side anastomosis reconstruction improved intraoperative flow and reduced pulsatility index in all the 14 patients significantly. The 16 patients who had the distal end side-to-side anastomoses performed directly also exhibited satisfactory intraoperative graft flow. Three-month postoperative outcomes for all the patients were satisfactory. Conclusions Side-to-side anastomosis at the distal end of sequential vein grafts might be a promising strategy to connect small target coronary arteries to the GSV. PMID:24884776

[Indication for exercise therapy in infancy in the prevention of childhood cerebral palsy].

PubMed

Weber, S

1983-01-01

As in physiotherapy of cerebral palsy early therapy is desired, if possible even in early infancy, a period, when a safe diagnosis does not yet exist, infants at risk have to be identified. The resulting difficulties in early diagnosis and inevitability of treating a considerable number of not affected infants are discussed. The most common methods of physiotherapy are briefly described and evaluated critically concerning possible side effects as well. Superiority in effectivity improving motor efficiency of one method over another cannot be proven. It is shown, however, that in the Vojta method adverse psychological side effects cannot be excluded. Therefore, physiotherapy being a purely prophylactic and not a therapeutic procedure in the multitude of cases should be considered in ordering and selecting a particular method and the one according to Bobath should be favoured.

Strategies to minimize cognitive side effects with ECT: aspects of ECT technique.

PubMed

Prudic, Joan

2008-03-01

The adverse cognitive effects of electroconvulsive therapy are important limitations in the use of this treatment that continues to be a significant therapeutic strategy after 7 decades of use. Among the approaches to mitigation of these side effects are considerations involving the prescription and manipulation of the electrical stimulus itself. The impact of the following electrical factors on the cognitive outcomes of electroconvulsive therapy are surveyed: efficiency of the stimulus as expressed in electrical waveform; targeting of the stimulus, the major concept underlying electrode placement; stimulus dosing; and frequency and number of treatments. The current state of development of knowledge in these areas is summarized, and methods to achieve the best cognitive outcomes without sacrificing clinical efficacy are discussed. Future trends in the further optimization of the electrical stimulus are briefly mentioned.

Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

PubMed

Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

2015-01-01

Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

PubMed

Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

2015-03-01

The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Open-label trial of atomoxetine hydrochloride in adults with ADHD.

PubMed

Johnson, Mats; Cederlund, Mats; Råstam, Maria; Areskoug, Björn; Gillberg, Christopher

2010-03-01

While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Ten patients met primary efficacy criteria at 10 weeks. Only one patient completed the whole study. Six patients discontinued before 10 weeks and thirteen at 10 weeks or later, mainly because of side-effects (aggression, depressed mood, raised liver enzymes, thyroid hormones, diastolic blood pressure), decreasing efficacy or non-compliance. Fifty percent responded to treatment, but only one patient (5%) felt sufficient improvement to continue for one year. Dosage may have been too low, and baseline impairment too high, for atomoxetine to have sufficient effect on ADHD symptoms in our group of adults. The majority had few side-effects, but several terminated treatment because of adverse effects.

Infant titi monkey behavior in the open field test and the effect of early adversity.

PubMed

Larke, Rebecca H; Toubiana, Alice; Lindsay, Katrina A; Mendoza, Sally P; Bales, Karen L

2017-09-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. © 2017 Wiley Periodicals, Inc.

The Zero-vision: potential side effects of communicating health perfection and zero risk.

PubMed

Fugelli, Per

2006-03-01

Public health education may have harmful side effects: generate fear, give rise to healthism and contribute to a medical sorting society. To prevent these adverse reactions a new deal for public health communication is presented. It is commended to move public health from omnipotence to moderation, from life style to living conditions, from risk to the bright sides of health, from statistical clone to the holy individual. Furthermore public health communication ought to include uncertainty as authoritarian truth mongering erodes trust. The public health educator must convey compassion and dedication. Rational techno-info is not sufficient. The last golden rule for a new public health is to respect the people. The people are not an inferior mass subjected to basic instincts and irrational fears. Common sense and lay experiences may contribute to the wise management of risk. Therefore public health should develop a people-centered method, recognizing people's own values, perceptions and potentials for preventing disease and promoting health.

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease.

PubMed

Oldham, Justin M; Lee, Cathryn; Valenzi, Eleanor; Witt, Leah J; Adegunsoye, Ayodeji; Hsu, Scully; Chen, Lena; Montner, Steven; Chung, Jonathan H; Noth, Imre; Vij, Rekha; Strek, Mary E

2016-12-01

Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown. A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models. Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement. A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Active Targeted Drug Delivery for Microbes Using Nano-Carriers

PubMed Central

Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

Practical Insight to Monitor Home NIV in COPD Patients.

PubMed

Arnal, Jean-Michel; Texereau, Joëlle; Garnero, Aude

2017-08-01

Home noninvasive ventilation (NIV) is used in COPD patients with concomitant chronic hypercapnic respiratory failure in order to correct nocturnal hypoventilation and improve sleep quality, quality of life, and survival. Monitoring of home NIV is needed to assess the effectiveness of ventilation and adherence to therapy, resolve potential adverse effects, reinforce patient knowledge, provide maintenance of the equipment, and readjust the ventilator settings according to the changing condition of the patient. Clinical monitoring is very informative. Anamnesis focuses on the improvement of nocturnal hypoventilation symptoms, sleep quality, and side effects of NIV. Side effects are major cause of intolerance. Screening side effects leads to modification of interface, gas humidification, or ventilator settings. Home care providers maintain ventilator and interface and educate patients for correct use. However, patient's education should be supervised by specialized clinicians. Blood gas measurement shows a significant decrease in PaCO 2 when NIV is efficient. Analysis of ventilator data is very useful to assess daily use, unintentional leaks, upper airway obstruction, and patient ventilator synchrony. Nocturnal oximetry and capnography are additional monitoring tools to assess the impact of NIV on gas exchanges. In the near future, telemonitoring will reinforce and change the organization of home NIV for COPD patients.

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

PubMed

Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

2017-06-01

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Single dose regorafenib-induced hypertensive crisis.

PubMed

Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

2014-06-01

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

Effect of heat input on dissimilar welds of ultra high strength steel and duplex stainless steel: Microstructural and compositional analysis

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

Tasalloti, H., E-mail: hamed.tasalloti.kashani@stu

The effect of heat input on the microstructure and compositional heterogeneity of welds of direct-quenched ultra high strength steel (Optim 960 QC) and duplex stainless steel (UNS S32205) was studied. The dissimilar welds were made using GMAW with a fully austenitic filler wire. In addition to grain coarsening in the heat affected zone (HAZ) of the ferritic side, it was found that an increase in heat input correlatively increased the proportional volume of bainitic to martensitic phases. Coarse ferritic grains were observed in the duplex HAZ. Higher heat input, however, had a beneficial effect on the nucleation of austenite inmore » the HAZ. Heat input had a regulatory effect on grain growth within the austenitic weld and more favorable equiaxed austenite was obtained with higher heat input. On the ferritic side of the welds, macrosegregation in the form of a martensitic intermediate zone was observed for all the cooling rates studied. However, on the duplex side, macrosegregation in the fusion boundary was only noticed with higher cooling rates. Microstructural observations and compositional analysis suggest that higher heat input could be beneficial for the structural integrity of the weld despite higher heat input increasing the extent of adverse coarse grains in the HAZ, especially on the ferritic side. - Highlights: •The effect of heat input on dissimilar welds of UHSS and DSS was studied. •Transmutation of the microstructure was discussed in detail. •The influence of heat input on compositional heterogeneity of welds was described. •Higher heat input enhanced bainitic transformation on the ferritic side. •Macrosegregation was affected by the amount of heat input on the DSS side.« less

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.

The pharmacoeconomics of peri-operative beta-blocker therapy.

PubMed

Biccard, B M; Sear, J W; Foëx, P

2006-01-01

It is widely recommended that beta-blockade be used peri-operatively as it may reduce the incidence of postoperative cardiovascular complications including death. However, there are few data concerning the cost-effectiveness of such strategies. We have analysed the pharmacoeconomics of acute beta-blockade using data from eight prospective peri-operative studies in which patients underwent elective non-cardiac surgery, and in which the incidence of adverse side-effects of treatment, as well as clinical outcomes, have been reported. The costs of treatment were based on the NHS reference costs for 2004. From these data, the number-needed-to-treat (NNT) to prevent a major cardiovascular complication (including cardiovascular death) in high-risk patients was 18.5. This is comparable to the NNT for peri-operative statin therapy. The incremental cost of peri-operative beta-blockade (costs of drug acquisition and of treating associated adverse drug events) was 67.80 pounds sterling per patient. This results in a total cost of 1254.30 pounds sterling per peri-operative cardiovascular complication prevented. However, there is evidence that in patients at lower cardiovascular risk, beta-blockers may be potentially harmful, since their adverse effects (hypotension, bradycardia) may outweigh their potential cardioprotective effects.

Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

PubMed

Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

2014-01-01

The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

Effects of Ionizing Radiation on the Heart

PubMed Central

Boerma, Marjan; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Nelson, Gregory A.; Cheema, Amrita K.; Koturbash, Igor; Singh, Sharda P.; Tackett, Alan J.; Hauer-Jensen, Martin

2016-01-01

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify noninvasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects. PMID:27919338

Clopidogrel-Induced Neutropenia after Coronary Stenting: Is Cilostazol a Good Alternative?

PubMed Central

Montalto, Massimo; Porto, Italo; Gallo, Antonella; Camaioni, Claudia; Della Bona, Roberta; Grieco, Antonio; Crea, Filippo; Landolfi, Raffaele

2011-01-01

Dual antiplatelet therapy with aspirin plus thienopyridines has become the standard treatment of patients undergoing coronary stenting. Clopidogrel has mostly replaced the use of ticlopidine due to its more favourable adverse event profile. However, also the use of clopidogrel is not without side effects. Clopidogrel major adverse events are represented by marrow suppression, manifesting with aplastic anaemia, thrombocytopenia and neutropenia. When clopidogrel toxicity occurs, there are few and unsubstantiated alternative treatments and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced bone marrow toxicity manifesting with severe neutropenia in a patient treated with multiple coronary stents and provide suggestions for an alternative treatment. PMID:21860799

Risperidone Versus Methylphenidate in Treatment of Preschool Children With Attention-Deficit Hyperactivity Disorder.

PubMed

Arabgol, Fariba; Panaghi, Leily; Nikzad, Vahid

2015-02-01

Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric diagnosis among preschool children. The aim of this study was to examine the Risperidone treatment compared to Methylphenidate (MPH) in preschool children with ADHD. Thirty three outpatient preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD was established by two child and adolescent psychiatrists according to the DSM-IV-TR criteria), participated in a 6-week, double-blind clinical trial with risperidone (0.5-1.5 mg/d) and methylphenidate (5-20 mg/d), in two divided doses. Treatment outcomes were assessed using the Parent ADHD Rating Scale and Conners Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks after the medication started. Side effects were also rated by side effects questionnaire. There were no significant differences between the two protocols on the Parent ADHD Rating Scale scores (P > 0.05) and Parent Conners Rating Scale scores (P > 0.05). Both groups showed a significant improvement in ADHD symptoms over the 6 weeks of treatment for parent ADHD Rating Scale (P < 0.001) and Parent Conners Rating Scale (P < 0.001). The most common adverse effects seen with risperidone were daytime drowsiness and anorexia (20%), and with methylphenidate it was anorexia (55%). Results of this study show that risperidone may be effective and well tolerated for ADHD in preschool children, but more researches are needed to clarify the potential benefits and adverse effects in long term use and comorbid conditions.

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

PubMed

Lodish, Maya B

2013-04-01

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

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

PubMed Central

Devabhakthuni, Sandeep

2013-01-01

The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects. PMID:24665213

Cimetidine: II. Adverse reactions and patterns of use.

PubMed

Freston, J W

1982-11-01

Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).

Development of Inhibitors of Salicylic Acid Signaling.

PubMed

Jiang, Kai; Kurimoto, Tetsuya; Seo, Eun-kyung; Miyazaki, Sho; Nakajima, Masatoshi; Nakamura, Hidemitsu; Asami, Tadao

2015-08-19

Salicylic acid (SA) plays important roles in the induction of systemic acquired resistance (SAR) in plants. Determining the mechanism of SAR will extend our understanding of plant defenses against pathogens. We recently reported that PAMD is an inhibitor of SA signaling, which suppresses the expression of the pathogenesis-related PR genes and is expected to facilitate the understanding of SA signaling. However, PAMD strongly inhibits plant growth. To minimize the side effects of PAMD, we synthesized a number of PAMD derivatives, and identified compound 4 that strongly suppresses the expression of the PR genes with fewer adverse effects on plant growth than PAMD. We further showed that the adverse effects on plant growth were partially caused the stabilization of DELLA, which is also related to the pathogen responses. These results indicate that compound 4 would facilitate our understanding of SA signaling and its cross talk with other plant hormones.

Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy.

PubMed Central

Mir, L. M.; Glass, L. F.; Sersa, G.; Teissié, J.; Domenge, C.; Miklavcic, D.; Jaroszeski, M. J.; Orlowski, S.; Reintgen, D. S.; Rudolf, Z.; Belehradek, M.; Gilbert, R.; Rols, M. P.; Belehradek, J.; Bachaud, J. M.; DeConti, R.; Stabuc, B.; Cemazar, M.; Coninx, P.; Heller, R.

1998-01-01

Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate. PMID:9649155

Intrathecal Baclofen Pump for Spasticity

PubMed Central

2005-01-01

Executive Summary Objective To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity. The Technology Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is administered orally, only a small portion of the original dose crosses the blood brain barrier and enters the central nervous system (CNS) fluid, which is the site of drug action. In order to bypass the oral route, baclofen may be administered intrathecally by infusion directly to the CNS. Candidates for intrathecal baclofen infusion are patients with spasticity who have intractable spasticity uncontrolled by drug therapy, or who experience intolerable side effects from oral baclofen. Advantages of intrathecal baclofen infusion are: Direct drug administration to the cerebrospinal fluid (CSF) The central side effects of oral baclofen, such as drowsiness or confusion, appear to be minimized with intrathecal administration. The intrathecal delivery of baclofen concentrates the drug in the CSF at higher levels than those attainable via the oral route. Intrathecal administration can use concentrations of baclofen of less than one hundredth of those used orally.(5) Adjustable/programmable continuous infusion makes it possible to finely titrate patients’ doses and to vary the doses over the hours of the day. For example, the dose can be relatively low to give the patients the extensor tone needed for ambulation during the day and increased at night, thereby improving quality of sleep. Reversible (in contrast to surgery). A patient who is a candidate for intrathecal baclofen infusion must have no contraindications to the insertion of an intrathecal catheter (e.g., anticoagulant therapy, coagulopathy, local or systemic infection, anatomical abnormality of the spine). Review Strategy The Medical Advisory Secretariat reviewed the literature to assess the effectiveness, safety, and cost-effectiveness of intrathecal baclofen to treat patients who have intractable spasticity uncontrolled by drug therapy, or who experience intolerable side effects to oral baclofen. The Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Summary of Findings Level 2 evidence supports the effectiveness of intrathecal baclofen infusion for the short-term reduction of severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen Level 3 evidence supports the effectiveness of intrathecal baclofen for the long-term reduction of severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen Level 4 qualitative evidence demonstrates functional improvement for patients who are unresponsive or cannot tolerate oral baclofen Intrathecal baclofen is cost-effective with costs which may or may not be avoided in the Ontario health system True functional use remains to be determined PMID:23074476

Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease.

PubMed

Gao, Jie; Adam, Bao-Ling; Terry, Alvin V

2014-03-15

The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

2010-01-01

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

Avoiding and treating dermal filler complications.

PubMed

Lemperle, Gottfried; Rullan, Peter P; Gauthier-Hazan, Nelly

2006-09-01

All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat.

The dark side of transparency: How and when pay administration practices affect employee helping.

PubMed

Bamberger, Peter; Belogolovsky, Elena

2017-04-01

This study examines a long-standing contention of practitioners and scholars alike, namely that pay transparency may adversely affect employees' tendency to offer assistance to coworkers. Drawing from research on social comparison, information vividness, and envy, we develop and test a moderated-mediation model positing that transparency adversely affects the amount of help individuals afford to peers who, based on pay for performance, are paid more than them. Testing our hypotheses in the context of a multiround simulation-based laboratory experiment, we find that this adverse effect of pay transparency on helping is largely explained by transparency's positive association with episodic envy, but only when individual differences grounded in differential social value orientations, specifically those regarding individualism beliefs and prosocial motivation, are taken into consideration. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pycnogenol may alleviate adverse effects in oncologic treatment.

PubMed

Belcaro, G; Cesarone, M R; Genovesi, D; Ledda, A; Vinciguerra, G; Ricci, A; Pellegrini, L; Gizzi, G; Ippolito, E; Dugall, M; Cacchio, M; Di Renzo, A; Stuard, S

2008-09-01

A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group. For all patients this was the first chemotherapy treatment period. The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group, though in many cases to a limited extent. The most prominent improvements were found for nausea, vomiting, diarrhoea and weight loss. Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group. Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia. Effects on anemia could not be investigated as several patients received erythrocyte transfusion. In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group (4% vs 19%). In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects. This was reflected by less days of hospitalisation the patients required. The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy. This possibility requires attention in future studies with Pycnogenol. From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection, and anti-inflammatory anti-edema activities. The results of this pilot trial warrant further prospective studies with larger number of patients to validate benefits more specifically with regard to type of malignancy and treatment regimen.

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

PubMed

Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

2016-06-22

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

The influence of narrative v. statistical information on perceiving vaccination risks.

PubMed

Betsch, Cornelia; Ulshöfer, Corina; Renkewitz, Frank; Betsch, Tilmann

2011-01-01

Health-related information found on the Internet is increasing and impacts patient decision making, e.g. regarding vaccination decisions. In addition to statistical information (e.g. incidence rates of vaccine adverse events), narrative information is also widely available such as postings on online bulletin boards. Previous research has shown that narrative information can impact treatment decisions, even when statistical information is presented concurrently. As the determinants of this effect are largely unknown, we will vary features of the narratives to identify mechanisms through which narratives impact risk judgments. An online bulletin board setting provided participants with statistical information and authentic narratives about the occurrence and nonoccurrence of adverse events. Experiment 1 followed a single factorial design with 1, 2, or 4 narratives out of 10 reporting adverse events. Experiment 2 implemented a 2 (statistical risk 20% vs. 40%) × 2 (2/10 vs. 4/10 narratives reporting adverse events) × 2 (high vs. low richness) × 2 (high vs. low emotionality) between-subjects design. Dependent variables were perceived risk of side-effects and vaccination intentions. Experiment 1 shows an inverse relation between the number of narratives reporting adverse-events and vaccination intentions, which was mediated by the perceived risk of vaccinating. Experiment 2 showed a stronger influence of the number of narratives than of the statistical risk information. High (vs. low) emotional narratives had a greater impact on the perceived risk, while richness had no effect. The number of narratives influences risk judgments can potentially override statistical information about risk.

Bad news: The influence of news coverage and Google searches on Gardasil adverse event reporting.

PubMed

Faasse, Kate; Porsius, Jarry T; Faasse, Jonathan; Martin, Leslie R

2017-12-14

Human papilloma virus vaccines are a safe and effective tool for reducing HPV infections that can cause cervical cancer. However, uptake of these vaccines has been suboptimal, with many people holding negative beliefs and misconceptions. Such beliefs have been linked with the experience of unpleasant side effects following medical treatment, and media coverage may heighten such concerns. The present study sought to assess the influence of news coverage (number of news articles per month) on adverse event reporting in response to Gardasil vaccination in New Zealand over a 7.5-year period, and whether the influence of news coverage was mediated by internet search activity (Google search volumes). Multiple linear regression analyses and simple mediation analyses were used, controlling for year and number of vaccinations delivered. News coverage in the previous month, and Google search volumes in the same month, were significant predictors of adverse event reporting, after accounting for vaccination rates and year. Concurrent Google search volumes partially mediated the effect of prior news coverage. The results suggest that some of the adverse events reported were not related to the vaccination itself, but to news coverage and internet search volumes, which may have contributed to public concerns about potentially unpleasant or harmful outcomes. These findings have implications for the importance of psychological and social factors in adverse event reporting, and the role of the news media in disseminating health information. Copyright © 2017 Elsevier Ltd. All rights reserved.

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

PubMed

Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

2016-10-21

Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

Early Diagnosis, Treatment and Care of Cancer Patients

DTIC Science & Technology

2008-09-01

these substances, and to determine whether parthenolide or parthenolide analogs enhance the damage caused by cytarabine . (Months 1-24) Progress...barrier. SOW task #2: Demonstrate that mice in which purified cells are more oxidized in vitro will exhibit more extensive damage from cytarabine ...risk for adverse side effects of therapy with W81XWH-07-1-0601 6 cytarabine , parthenolide (or parthenolide analogs) or the combination of these

Steam inhalation therapy: severe scalds as an adverse side effect

PubMed Central

Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

2012-01-01

Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study.

PubMed

van Nes, J G H; Fontein, D B Y; Hille, E T M; Voskuil, D W; van Leeuwen, F E; de Haes, J C J M; Putter, H; Seynaeve, C; Nortier, J W R; van de Velde, C J H

2012-07-01

Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch postmenopausal early breast cancer patients were randomized between 5 years of exemestane, or tamoxifen (2.5-3 years) followed by exemestane (2.5-2 years). 742 patients were invited to participate in the QoL side study and complete questionnaires at 1 (T1) and 2 (T2) years after start of endocrine treatment. Questionnaires comprised the EORTC QLQ-C30 and BR23 questionnaires, supplemented with FACT-ES questions. 543 patients completed questionnaires at T1 and 454 patients (84%) at T2. Overall QoL and most functioning scales improved over time. The only clinically relevant and statistically significant difference between treatment types concerned insomnia; exemestane-treated patients reported more insomnia than tamoxifen-treated patients. Discrepancy was observed between QoL issue scores reported by the patients and adverse events reported by physicians. Certain QoL issues are treatment- and/or time-specific and deserve attention by health care providers. There is a need for careful inquiry into QoL issues by those prescribing endocrine treatment to optimize QoL and treatment adherence.

The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

PubMed

Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

2017-09-01

People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

Complications of local anaesthesia. An observational study.

PubMed

Brand, H S; Bekker, W; Baart, J A

2009-11-01

Local anaesthesia is increasingly used by dental hygienists. As little is known about the incidence of adverse effects during and after the administration of local anaesthetics, we evaluated side-effects associated with local anaesthesia. A prospective observational study was conducted using standard criteria among a group of 103 patients receiving mandibular block anaesthesia. Physical reactions like clenching fists (14.5%), moaning (12.6%) and turning pale (7.8%) were frequently observed. Patients (3.8%) showed a painful reaction because of needle contact with a nerve or the periosteum. Systemic complications were not observed. After the injection, 41.7% said they felt tense during the administration; 4.9% of the patients reported swallowing problems and 3.9% a tachycardia. These results suggest that administration of local anaesthesia has a small risk of adverse events. Complications, if they occur, seem minor and transient in nature.

Use of 4MAT Learning Theory to Promote Better Skin Care During Radiation Therapy: An Evidence-Based Quality Improvement Project.

PubMed

Bauer, Carole; Magnan, Morris; Laszewski, Pamela

Radiation therapy is a key treatment modality for cancer patients, but it is associated with adverse side effects such as radiation dermatitis. To mitigate the adverse effects of radiation on the skin, patients must participate in skin-related self-care. However, even with self-care instruction, adherence can be poor. This quality improvement project used best available evidence for skin care in patients undergoing radiation therapy and a theoretical framework, 4MATing, to provide a structured approach to patient education designed to enhance adherence to skin care recommendations. Implementation of this approach resulted in increased adherence to a topical skin care protocol in our facility. Patients were highly satisfied with their education. While there was a 4-day delay in the onset of radiation dermatitis, this difference was not statistically significant.

The androgen-deficient aging male: current treatment options.

PubMed

Tenover, J Lisa

2003-01-01

All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring.

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able to help support early SAR to accelerate drug discovery and decrease late stage attrition in drug discovery projects. In addition, models such as the ones presented here can be used for compound profiling in all development stages.

Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices?

PubMed

González, Mónica; Macias-Escalada, Emilio; Cobo, Juan; Fernández Mondragón, Maria Pilar; Gómez-Moreno, Gerardo; Martínez-Martínez, Marian; de Carlos, Felix

2016-12-01

Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p < 0.001). The risk of suffering muscular alterations during oral device treatment is higher in statin patients (odds ratio 6.67, p = 0.002). Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices.

Proton Pump Inhibitors: Risk for Myopathy?

PubMed

Colmenares, Evan W; Pappas, Ashley L

2017-01-01

The purpose of this article is to describe the relationship between proton pump inhibitors (PPIs) and symptoms of myopathy based on case reports. A literature search was conducted in PubMed (1946 to June 2016) using MeSH terms proton pump inhibitors, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, and muscular diseases. Additionally, a search was conducted in ToxNet and EMBASE using similar search criteria. The resulting articles were scanned to assess relevance to the review. Bibliographies of all relevant articles were evaluated for additional sources; 26 articles resulted from the search of PubMed, ToxNet, and EMBASE; articles that involved medications typically considered to have myalgia-like side effects (eg, statins), or included patients who presented with a confounding disease state (eg, Guillain-Barré) were excluded. In total, 11 case reports as well as a review of an adverse event reporting database that included 292 cases were evaluated. Association of PPI use and myopathy symptoms does not have a clear etiology. Overall, the available published data do not show a high risk of myopathy with PPI use but should be considered if a patient presents with myopathy symptoms and concurrent PPI use. A limited body of published data suggests that PPI use has been associated with myopathy-like symptoms without long-term effects following discontinuation. Although myopathy is a rare adverse effect observed with PPIs, it can be a serious side effect to be considered when starting a patient on acid suppression therapy.

A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression.

PubMed

Barclay, Timothy H; Barclay, Raymond D

2014-08-01

Anxiety disorders are among the most prevalent mental disorders and are usually treated with medication and/or psychotherapy. When anxiety disorders are accompanied with comorbid depression, this further complicates the treatment process. Medication compliance is a common problem due to adverse side effects and new and effective treatments that have minimal side effects are needed for the treatment of anxiety and depression. This study used a randomized, double-blind, sham controlled design to examine the effectiveness of CES as a treatment for anxiety disorders and comorbid depression in a primary care setting. The study was registered at clinicaltrials.gov, NCT01533415. One hundred and fifteen participants, age 18 years and over, with a primary diagnosis of an anxiety disorder were enrolled from February 2012 to December 2012 The Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Depression Rating Scale17 (HAM-D17) were used for baseline and outcome measures at weeks one, three, and five. Response to treatment was defined as a reduction of ≥50% or more on these measures. Analysis of covariance revealed a significant difference between the active CES group and the sham CES group on anxiety (p=0.001, d=0.94) and on depression (p=0.001, d=0.78) from baseline to endpoint of study in favor of the active CES group. CES significantly decreases anxiety and comorbid depression. Subjects reported no adverse events during the study. Copyright © 2014 Elsevier B.V. All rights reserved.

Carbonic anhydrase inhibition: insight into non-COX-2 pharmacological effect of some coxibs.

PubMed

Dogné, Jean-Michel; Thiry, Anne; Supuran, Claudiu T

2008-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described adverse drug reactions (ADRs) limit their use. These drugs act via the inhibition of cyclooxygenase (COX) enzyme of which at least two isoforms were described: COX-1 which plays important roles in homeostatic processes such as thrombogenesis and homeostasis of the gastrointestinal tract and kidneys and COX-2 expressed in pathological conditions such as inflammation or cancer proliferation. Selective COX-2 inhibitors or "coxibs" were initially developed as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of non specific NSAIDs. However, this class of drug did not fulfill all their promises. Indeed, numerous unexpected side effects have limited their use and some of them have been withdrawn or suspended from the market for different safety reasons including cardiovascular, hepatic and skin adverse reactions. For instance, cardiovascular warnings have been applied to the whole class of coxibs and more recently for all classical NSAIDs as well. However, differences in the chemical structures should be taken into consideration in order to discriminate between coxibs and the development of some ADRs of which renal events and hypertension. The aim of this paper is to focus on the differences in chemical structures of all marketed COX-2 inhibitors and their unexpected effects on carbonic anhydrase in order to provide non-COX-2 mechanistic insights into some of the differences observed between coxibs.

Gastrointestinal toxicity after vincristine or cyclophosphamide administered with or without maropitant in dogs: a prospective randomised controlled study.

PubMed

Mason, S L; Grant, I A; Elliott, J; Cripps, P; Blackwood, L

2014-08-01

To assess the prevalence of gastrointestinal toxicity in dogs receiving chemotherapy with vincristine and cyclophosphamide and the efficacy of maropitant citrate (Cerenia™, Zoetis) in reducing these events. Dogs receiving chemotherapy with cyclophosphamide or vincristine were randomised to either receive maropitant or not in the period immediately after treatment and for 4 days afterwards. Owners completed a diary of adverse events following treatment. Adverse events occurred in 40/58 (69%) dogs in the vincristine group. Most of these adverse events were mild and included: lethargy (62%), appetite loss (43%), diarrhoea (34%) and vomiting (24%). Adverse events occurred in 34/42 (81%) dogs treated with cyclophosphamide. Most of these adverse events were mild and included: lethargy (62%), diarrhoea (36%), appetite loss (36%) and vomiting (21%). There was no difference in total clinical score, vomiting, diarrhoea, appetite loss or lethargy score between dogs treated with maropitant and non-treated dogs in either the vincristine or cyclophosphamide groups. Chemotherapy-related side effects are frequent but usually mild in dogs receiving vincristine or cyclophosphamide. Prophylactic administration of maropitant does not reduce the frequency of adverse events and maropitant should be administered only as required for individual cases. © 2014 British Small Animal Veterinary Association.

Changes in behavior as side effects in methylphenidate treatment: review of the literature

PubMed Central

Konrad-Bindl, Doris Susanne; Gresser, Ursula; Richartz, Barbara Maria

2016-01-01

Background Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes in the pediatric, adolescent, and adult populations. Materials and methods We conducted a literature search in PubMed, Medline, and Google using the keywords “methylphenidate”, “behavioral changes”, “adverse effects”, and “side effects”. A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis. Results Five studies specifically set out to study, record, and discuss changes in behavior. Eight studies did not set out to study behavioral effects, but record and discuss them. A total of 28 studies recorded behavioral effects, but failed to discuss these further. Three studies did not include behavioral effects. Conclusion This review records what data have been published in respect of changes in behavior in association with the use of methylphenidate. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of methylphenidate taking. PMID:27789952

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

PubMed

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

2009-06-01

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

Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation.

PubMed

Jones, Rachel; Prommer, Eric; Backstedt, David

2016-11-01

Opioid-related bowel dysfunction is a common and potentially severe adverse effect from treatment with opioid analgesics. Its development is not dose related, nor do patients develop tolerance. Opioid-induced constipation (OIC) can lead to fecal impaction, bowel obstruction, and bowel perforation as well as noncompliance with opioid analgesics and poor quality of life. Routine administration of laxatives is necessary to maintain bowel function, and, in refractory cases, other modalities must be pursued. Available options are limited but include peripherally acting μ-opioid receptor antagonists (PAMORAs), including methylnaltrexone. Naloxegol is a newly developed PAMORA that is available through the oral route. At the therapeutic dose of 25 mg daily, naloxegol is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia. In this article, we discuss the pharmacokinetics, pharmacodynamics, adverse effects, clinical trials, and cost considerations of naloxegol. Finally, we discuss its potential role as a novel key treatment for OIC in palliative medicine patients. © The Author(s) 2015.

Cognitive functioning after subthalamic nucleotomy for refractory Parkinson's disease

PubMed Central

McCarter, R.; Walton, N.; Rowan, A.; Gill, S.; Palomo, M.

2000-01-01

OBJECTIVE—To evaluate whether subthalamic nucleotomy produces adverse cognitive effects in patients with Parkinson's disease.
METHOD—Twelve patients with Parkinson's disease underwent stereotactic surgery to the subthalamic nucleus. Presurgical and postsurgical neuropsychological assessment of attention, memory, executive function, language, and verbal intellect were undertaken with a battery of tests designed to minimise potential contamination of cognitive effects by motor symptoms.
RESULTS—There was no statistically significant difference in the cognitive tests results after operation for the group as a whole. Reliable change indexes were generated for the cognitive tests. Reliable change postoperatively was found on specific tests of verbal memory, attention, and planning. Left sided operations were associated with greater incidence of deterioration postsurgery.
CONCLUSIONS—Preliminary data on the first reported cognitive changes after subthalamic nucleotomy suggested few adverse cognitive effects of the surgery although discrete neuropsychological changes were seen in some patients. These effects were consistent with current theories on the cognitive functions of the basal ganglia.

 PMID:10864605

Adverse Event extraction from Structured Product Labels using the Event-based Text-mining of Health Electronic Records (ETHER)system.

PubMed

Pandey, Abhishek; Kreimeyer, Kory; Foster, Matthew; Botsis, Taxiarchis; Dang, Oanh; Ly, Thomas; Wang, Wei; Forshee, Richard

2018-01-01

Structured Product Labels follow an XML-based document markup standard approved by the Health Level Seven organization and adopted by the US Food and Drug Administration as a mechanism for exchanging medical products information. Their current organization makes their secondary use rather challenging. We used the Side Effect Resource database and DailyMed to generate a comparison dataset of 1159 Structured Product Labels. We processed the Adverse Reaction section of these Structured Product Labels with the Event-based Text-mining of Health Electronic Records system and evaluated its ability to extract and encode Adverse Event terms to Medical Dictionary for Regulatory Activities Preferred Terms. A small sample of 100 labels was then selected for further analysis. Of the 100 labels, Event-based Text-mining of Health Electronic Records achieved a precision and recall of 81 percent and 92 percent, respectively. This study demonstrated Event-based Text-mining of Health Electronic Record's ability to extract and encode Adverse Event terms from Structured Product Labels which may potentially support multiple pharmacoepidemiological tasks.

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.

Biased mu-opioid receptor ligands: a promising new generation of pain therapeutics.

PubMed

Siuda, Edward R; Carr, Richard; Rominger, David H; Violin, Jonathan D

2017-02-01

Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events. In this review we summarize these concepts with an emphasis on biased mu opioid receptor pharmacology and highlight how far opioid pharmacology has evolved. Copyright © 2016 Elsevier Ltd. All rights reserved.

49 CFR 178.603 - Drop test.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the fourth sample). Fifth drop: On a corner (using the fifth sample). Bags—single-ply with a side seam...). Bags—single-ply without a side seam, or multi-ply Three—(two drops per bag) First drop: Flat on a wide...) For a bag, neither the outermost ply nor an outer packaging exhibits any damage likely to adversely...

Safety of the electroconvulsive therapy and amisulpride combination.

PubMed

Takács, Rozália; Iványi, Zsolt; Ungvari, Gabor S; Gazdag, Gábor

2013-03-01

Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. All adverse effects resolved within 24 hours. No side effects of any kind were observed in 7 and 8 cases in the study and control groups, respectively. This was the first study that examined the safety of amisulpride-ECT combination in schizophrenia. Comparing the side-effects between the study and control groups, no significant differences were detected in terms of their types or frequency. The amisulpiride-ECT combination appears to be a safe treatment option.

The use of molindone in the treatment of psychotic and delirious patients infected with the human immunodeficiency virus. Case reports.

PubMed

Fernandez, F; Levy, J K

1993-01-01

Four patients with HIV infection and psychosis from various etiologies, refractory to standard treatments, and suffering from severe extrapyramidal symptoms (EPS), had a marked beneficial response to molindone. There was significant control of neuropsychiatric dysfunction without major adverse side effects. The results suggest that further evaluation is warranted of the use of molindone in treating severely ill, psychotic, or delirious HIV-infected patients.

Benefits of and Barriers to Pharmacogenomics-Guided Treatment for Major Depressive Disorder.

PubMed

Ahmed, Ahmed T; Weinshilboum, Richard; Frye, Mark A

2018-05-01

Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug-related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall "value equation," and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Seizures as a Potential Complication of Treatment With Simeprevir and Sofosbuvir.

PubMed

Syal, Gaurav; Heldenbrand, Seth D; Duarte-Rojo, Andres

2016-01-01

Newer direct-acting antiviral agents have revolutionized the medical management of chronic hepatitis C. In addition to being extremely efficacious, they report very mild adverse drug reactions from experience in clinical trials. However, because they are relatively new on the horizon, postmarketing surveillance studies refining the safety profile are not yet available. We present a case of seizures as a potential side effect of antiviral therapy with sofosbuvir and simeprevir.

Split-face comparison between single-band and dual-band pulsed light technology for treatment of photodamage.

PubMed

Varughese, Neal; Keller, Lauren; Goldberg, David J

2016-08-01

Intense pulsed light (IPL) has a well-recognized role in the treatment of photodamaged skin. To assess the safety and efficacy of a novel single-band IPL handpiece versus dual-band IPL handpiece in the treatment of photodamage. This was a prospective, single-center split-face study with 20 enrolled participants. Three treatments, 21 days apart, were administered to the subjects and follow-up was performed for 20 weeks. The left side of the face was treated with the single-band handpiece. The right side of the face was treated with the dual-band handpiece. Blinded investigators assessed the subjects' skin texture, pigmented components of photodamage, and presence of telangiectasia both before and after treatment, utilizing a five-point scale. Pigmented components of photodamage, skin texture, and presence of telangiectasias on the left and right side of the face were improved at the end of treatment. At 20-week follow-up, the side treated with single-band handpiece showed improvement in telangiectasia and pigmentation that was statistically superior to the contralateral side treated with the dual-band handpiece. Both devices equally improved textural changes. No adverse effects were noted with either device. Both single-band and dual-band IPL technology are safe and effective in the treatment of photodamaged facial skin. IPL treatment with a single-band handpiece yielded results comparable or superior to dual-band technology.

In elective arch surgery with circulatory arrest, does the arterial cannulation site really matter? A propensity score analysis of right axillary and innominate artery cannulation.

PubMed

Preventza, Ourania; Price, Matt D; Spiliotopoulos, Konstantinos; Amarasekara, Hiruni S; Cornwell, Lorraine D; Omer, Shuab; de la Cruz, Kim I; Zhang, Qianzi; Green, Susan Y; LeMaire, Scott A; Rosengart, Todd K; Coselli, Joseph S

2018-05-01

The preferred arterial cannulation site for elective proximal aortic procedures requiring circulatory arrest varies, and different sites have been tried. We evaluated the relationships between arterial cannulation site and adverse outcomes, including stroke, in patients undergoing elective aortic arch surgery. We reviewed the records of 938 patients who underwent elective hemiarch or total arch surgery with circulatory arrest between 2006 and 2016. Five cannulation sites were used: the right axillary (n = 515; 54.9%), innominate (n = 376; 40.1%), and right common carotid arteries (n = 15; 1.6%), each with a side graft; the ascending aorta (n = 19; 2.0%); and the femoral artery (n = 13; 1.4%). Multivariable logistic regression analysis was used to model the effects of cannulation site on adverse outcomes for the entire cohort and for a subcohort of 891 patients who underwent innominate or axillary artery cannulation. Propensity-matching yielded 564 patients (282 pairs) from the right axillary and innominate artery groups. For the entire cohort, mortality, stroke, and composite adverse outcome (operative death or persistent stroke or renal failure at hospital discharge) rates were 7.0%, 4.1%, and 9.8%. In the multivariable analysis of the axillary/innominate subcohort, cannulation site did not independently predict operative mortality, persistent stroke, or composite adverse event. These results were confirmed with the propensity-matched analysis, where both axillary and innominate artery cannulation provided equivalent composite adverse event rates, operative death rates, and overall stroke rates. During elective arch surgery, right axillary artery cannulation and innominate artery cannulation (both via a side graft) produce excellent results and can be used interchangeably. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A Review on the Traditional Chinese Medicinal Herbs and Formulae with Hypolipidemic Effect

PubMed Central

Sham, Tung-Ting; Chan, Chi-On; Wang, You-Hua; Yang, Jian-Mei; Mok, Daniel Kam-Wah; Chan, Shun-Wan

2014-01-01

Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the dominant factors of many chronic diseases such as diabetes, obesity, and cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side effects, the popularity of using traditional Chinese medicine (TCM) to handle hyperlipidemia is increasing and its role in health care has been recognized by the public at large. Despite the importance of TCM herbs and formulations, there is no comprehensive review summarizing their scientific findings on handling hyperlipidemia. This review summarizes the recent experimental and clinical results of nine representative single Chinese herbs and seven classic TCM formulae that could improve lipid profiles so as to help understand and compare their underlying mechanisms. Most of single herbs and formulae demonstrated the improvement of hyperlipidemic conditions with multiple and diverse mechanisms of actions similar to conventional Western drugs in spite of their mild side effects. Due to increasing popularity of TCM, more extensive, well-designed preclinical and clinical trials on the potential synergistic and adverse side effects of herb-drug interactions as well as their mechanisms are warranted. Hyperlipidemic patients should be warned about the potential risks of herb-drug interactions, particularly those taking anticoagulants and antiplatelet drugs. PMID:25110708

The effect of mobile phone to audiologic system.

PubMed

Kerekhanjanarong, Virachai; Supiyaphun, Pakpoom; Naratricoon, Jantra; Laungpitackchumpon, Prinya

2005-09-01

Mobile phones have come into widespread use. There are a lot of possible adverse effect to health. Use of mobile phone generate potentially harmful radiofrequency electromagnetic field (EMF) particularly for the hearing aspect. 98 subjects underwent hearing evaluations at Department of Otolaryngology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University. 31 males and 67females, mean age was 30.48 +/- 9.51 years old, all subjects were investigated the hearing level by audiometry, tympanometry, otoacoustic emission (OAE) and auditory brain stem evoked response (ABR). The average of using time were 32.54 +/- 27.64 months, 57 subjects usually used the right side and 41 the left side. Average time of use per day was 26.31 +/- 30.91 minutes (range from 3 to 180 mins). When the authors compared the audiogram, both pure tone and speech audiometry, between the dominant and nondominant side, it indicated that there is no significant different. When the authors focused on the 8 subjects that used the mobile phone more than 60 mins per day. It indicated that the hearing threshold of the dominant ears was worse than the nondominant ears.

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

PubMed

Sanacora, G; Smith, M A; Pathak, S; Su, H-L; Boeijinga, P H; McCarthy, D J; Quirk, M C

2014-09-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Antipsychotics and physical attractiveness.

PubMed

Seeman, Mary V

2011-10-01

Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

Tracking Pulse Oximeter Findings Before, During and After Titration of Mandibular Advancement Devices (MAD) for Patients With Mild to Moderate Obstructive Sleep Apnea (OSA)

DTIC Science & Technology

2015-06-01

CP AP because of claustrophobia, noise, nose bleeds, dermatitis and nasal bridge sores. In many cases, these effects are due to incorrect pressure...checked for contact data in case a subject must be contacted due to scheduling problems, or some new information is learned that a subject needs to know...Subject initiated contacts via phone or email to the PI with respect to adverse events, side effects or questions will be recorded on an electronic log

Hypoglycaemia: an overview.

PubMed

Graveling, Alex J; Frier, Brian M

2009-08-01

Hypoglycaemia is a frequent side-effect of treatment with insulin and sulfonylureas for people with diabetes, threatening potentially serious morbidity and preventing optimal glycaemic control. Fear of hypoglycaemia and development of syndromes such as impaired awareness and counterregulatory deficiency provide additional hazards for intensification of treatment. Rapid lowering of HbA1c may be potentially dangerous in type 2 diabetes because of the adverse cardiovascular effects induced by hypoglycaemia. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and recreational pursuits. Measures to reduce the risk of hypoglycaemia are labour-intensive and require substantial resources.

Ocular manifestations of drug and alcohol abuse

PubMed Central

Peragallo, Jason; Biousse, Valérie; Newman, Nancy J.

2015-01-01

Purpose of review To review commonly encountered adverse ocular effects of illicit drug use. Recent findings Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called “designer,” drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. Summary In this review we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them. PMID:24100364

First preliminary results of an observation of Panax ginseng treatment in patients with autistic disorder.

PubMed

Niederhofer, Helmut

2009-01-01

Autism is a pervasive developmental disorder, with impairments in reciprocal social interaction and verbal and nonverbal communication. There is often the need of psychopharmacological intervention in addition to psychobehavioral therapies, but benefits are limited by adverse side effects. For that reason, Panax ginseng, which is comparable with Piracetam, a substance effective in the treatment of autism, was investigated for possible improvement of autistic symptoms. There was some improvement, which suggests some benefits of Panax ginseng, at least as an add-on therapy.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

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

2011-01-01

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

The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

PubMed Central

de León-Casasola, Oscar A; Mayoral, Victor

2016-01-01

Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. PMID:26929664

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

PubMed Central

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. PMID:29491719

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

PubMed

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca; Setia, Sajita

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.

Management of a hyperactive teen and cardiac safety.

PubMed

Sowinski, Heather; Karpawich, Peter P

2014-02-01

Since the earliest descriptions of the condition, controversy has prevailed as to the existence of as well as appropriate management of attention deficit hyperactivity disorder. Often diagnosed in childhood, symptoms of attention deficit hyperactivity disorder can continue into adolescence and adulthood, requiring lifelong therapy. Effective therapeutic interventions include stimulant medications with all their respective potential side effects, including the cardiovascular system. However, although initial studies raised concerns for an increase in serious adverse cardiovascular effects among children receiving these drugs, more recent and extensive reports have failed to substantiate those findings among young patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Nutrients for prevention and treatment of mental health disorders.

PubMed

Akhondzadeh, Shahin; Gerbarg, Patricia L; Brown, Richard P

2013-03-01

The choice of nutrients for review is based on clinical evidence of efficacy in neuropsychiatric disorders and biochemical effects that are neuroprotective or reparative. Vitamins, minerals, amino acids, and metabolites have been shown to augment antidepressants, improve symptoms in anxiety disorders, depression, neurodegenerative diseases, brain injury, ADHD, and schizophrenia, and to reduce medication side effects. Detection and correction of vitamin and mineral deficiencies can be essential for recovery. Generally low in adverse effects when taken in therapeutic doses, nutrients can be combined for greater benefits. Further studies are warranted to validate these promising treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

[Herbal preparations have both effects and side effects. Widespread usage dictates knowledge among physicians].

PubMed

Mattsson, Karin; Nilsson, Inger

2002-12-12

The article gives a clinically oriented overview of the efficacy and safety of Ginkgo biloba, St. John's wort, ginseng, Echinacea, saw palmetto and kava based on American experiences. Clinical data support the efficacy for some of these drugs. None of them is free of adverse effects. Generally speaking, trials of herbal medicinal products have been too few, too small and too short. The lack of long-term studies is especially unfortunate since many of the drugs are used for a long time. The difference between American and Swedish legislation on herbal medicine products is described.

[Utilization of methylphenidate(Ritalin) in France].

PubMed

Frances, C; Hoizey, G; Millart, H; Trenque, T

2002-01-01

Methylphenidate (Ritalin) is the only psychostimulant approved in France and indicated in attention deficit hyperactivity disorder in children over 6 years. It is under restricted prescription and distribution conditions. As such, it requires a hospital initiated prescription from either a neurology, psychiatry or pediatric specialist and it is covered by the "narcotics" schedule. The French Pharmacovigilance database spontaneous adverse drug reactions reporting, since it was approved in 1995, were analyzed. 21 adverse drug reactions were reported. In 16 cases, methylphenidate was suspected. They were generally non-serious, mild side effects and in most cases promptly resolved. These results do not suggest methylphenidate misuse in France or an overuse in between 1300 and 4000 treated children, to date. Until more information is available concerning the long-term effects of methylphenidate, and in order to limit misuse, inappropriate or overuse, the current prescription and dispensing regulation should be maintained in France, and could well be developed in other countries.

Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.

PubMed

Chung, Jong Yoon; Lee, Jong Hee; Lee, Joo Heung

2016-08-01

Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.

Pain difference associated with injection of abobotulinumtoxinA reconstituted with preserved saline and preservative-free saline: a prospective, randomized, side-by-side, double-blind study.

PubMed

Allen, Shawn B; Goldenberg, Neil A

2012-06-01

The Food and Drug Administration has approved the reconstitution of botulinum toxin A with preservative-free saline. Reconstitution of onabotulinumtoxinA with preserved saline has been previously reported to decrease the pain of injections. We present the first split-face study investigating differences in subjective pain when using preserved and preservative-free saline as the reconstituent of choice for abobotulinumtoxinA. To determine whether patients notice a difference in pain when injecting abobotulinumtoxinA diluted with preserved saline versus preservative-free saline. A prospective, randomized, double-blind, side-by-side trial was conducted in a private practice dermatology office in Boulder, Colorado. Twenty volunteer patients received injections on one side of their face with abobotulinumtoxinA reconstituted with preservative-free saline and with abobotulinumtoxinA reconstituted with preserved saline on the other side. Patients reported their pain on a 10-point visual analogue pain scale after each side was injected. Patients kept a diary for the first 48 hours after treatment to track any continued pain, onset of action, or adverse events. Patients were seen at a follow-up visit at 2 weeks, and any adverse events were recorded. Ninety percent of patients reported less pain on the side injected with preserved saline than on the side injected with preservative-free saline. Pain on the preserved saline side was 60% less than on the preservative-free side. Neither the patients nor the investigators noted any difference in onset of action between the two sides. Reconstitution of abobotulinumtoxinA with preserved saline results in significantly less pain on injection than with preservative-free saline. Preserved saline may be the reconstituent of choice for reconstitution of abobotulinumtoxinA. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Geospatial analysis of creeks evolution in the Indus Delta, Pakistan using multi sensor satellite data

NASA Astrophysics Data System (ADS)

Ijaz, Muhammad Wajid; Mahar, Rasool Bux; Siyal, Altaf Ali; Anjum, Muhammad Naveed

2018-01-01

Sea level rise (SLR) in response to looming climate change is being considered as a major impediment to coastal areas. Acute wave activities and tidal propagations of semi-diurnal to mixed type are impairing the morphology of the Indus Delta in Pakistan. In this study a synthetic approach has been adopted using multi sensor satellite and ground data in order to integrate the individual effect of topography, oceanic activities and vegetative canopy for deduction of a synergic impact over the morphology of the Indus Delta creeks system from 1972 to 2017. Geomorphologic anomalies in the planform of fourteen major creeks were explored. Spatiotemporal variations suggested that a substantial amount of the delta alluvium had been engulfed by the Arabian Sea. On average, the creeks located on the right side of the Indus River were relatively less wide (3.9 km) than those of on the left side (5.2 km). Zonal statistics calculated with topographic position index (TPI) enabled to understand the tide induced inundation extents. The mangrove canopy on the right side was found greater, which is why tidal basins on that side experienced less erosive activities. Thus, it could be maintained that the coastal sedimentary processes may be monitored effectively with the remotely sensed data and temporal pattern of changes can be quantified for future planning and mitigation of adverse effects.

Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Deng, Jiaqi; Yan, Qiong; Yang, Chun; Xia, Guodong; Zhou, Xian

2016-01-01

Background Traditional Helicobacter pylori (H. pylori) eradication therapies have shown efficacies below 80% in several studies, and their use has been accompanied by antibiotic-related side effects. Some recent studies have reported that supplementing standard therapies with probiotics can improve the efficacy and tolerability of Helicobacter pylori eradication therapy. Objective To assess the effects of probiotic supplementation on the eradication rates and therapy-related adverse event rates of anti-Helicobacter pylori regimens. Methods We searched PubMed, Medline, the Cochrane Central Registry of Controlled Trials and the Chinese Biomedical Database for eligible randomized controlled trials published through July, 2015. Review Manager 5.3 was used for all statistical analyses. Results Thirteen randomized controlled trials involving a total of 2306 patients were included in our analysis. Intent-to-treat (ITT) analysis performed using a fixed-effects model (test for heterogeneity I2 = 45%) showed that the pooled relative risk (RR) of eradication was significantly higher in the probiotic supplementation group than in the control group [RR 1.15, 95% confidence interval (CI): 1.10–1.20, P<0.00001]. The incidence of total antibiotic-related side effects was lower in the probiotic supplementation group than in the control group, and the pooled RR (studies n = 9) was 0.71 (95% CI: 0.54–0.94, P = 0.02), as determined using a random-effects model (heterogeneity test I2 = 59%). Certain adverse events, such as nausea and vomiting (RR = 0.58, 95% CI 0.35–0.95, P = 0.03), diarrhea (RR = 0.51, 95% CI: 0.31–0.84, P = 0.008) and constipation (RR = 0.47, 95% CI: 0.28–0.80, P = 0.005), were reported at lower rates in the probiotic supplementation group than in the control group. Subgroup analysis showed that eradication rates were significantly improved in both adults (RR = 1.14, 95% CI: 1.09–1.19, P<0.00001) and children (RR = 1.24, 95% CI: 1.05–1.47, P = 0.01) in the probiotic supplementation group and that no regional differences between Europe (RR = 1.17, 95% CI: 1.09–1.24, P<0.00001) and Asia were present (RR = 1.14, 95% CI: 1.06–1.22, P = 0.0002). However, the total adverse event rate was not decreased in the adult group (RR = 0.80, 95% CI: 0.61–1.04, P = 0.1) or the Asian group (RR = 0.68, 95% CI: 0.39–1.18, P = 0.17). Subgroup analyses examining therapy regimens and treatment durations showed that probiotic supplementation increased eradication rates in the triple-therapy (RR = 1.18, 95% CI: 1.12–1.25, P<0.00001), seven-day treatment (RR = 1.21, 95% CI: 1.12–1.31, P<0.00001) and fourteen-day treatment (RR = 1.13, 95% CI: 1.06–1.20, P = 0.0002) groups. The incidence of antibiotic-related side effects was significantly reduced in all groups, with the exception of the quadruple-therapy subgroup (RR = 1.13, 95% CI: 0.60–2.13, P = 0.07) and the fourteen-day therapy subgroup (RR = 0.96, 95% CI 0.61–1.51, P = 0.86). Supplementation with Lactobacillus alone (RR = 1.24, 95% CI: 1.12–1.38, P<0.0001) or multi-strain probiotics (RR = 1.12, 95% CI 1.07–1.18, P<0.00001) was effective at improving H. pylori eradication rates. However, supplementation with Lactobacillus alone did not significantly decrease the overall incidence of side effects (RR = 0.61, 95% CI: 0.11–3.51, P = 0.58). Our study also showed that probiotic supplementation before, during or after H. pylori eradication therapy improved eradication rates, regardless of supplementation duration. Furthermore, probiotic supplementation during H. pylori treatment reduced the incidence of side effects. Conclusion Probiotic supplementation during anti-Helicobacter pylori treatment may be effective for improving H. pylori eradication rates, minimizing the incidence of therapy-related adverse events and alleviating most disease-related clinical symptoms. However, our results should be interpreted with caution because of the presence of heterogeneity across the trials included in this analysis. PMID:27723762

Evaluation of perampanel in patients with intellectual disability and epilepsy.

PubMed

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

2017-01-01

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

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

PubMed

Park, Subin; Kim, Bung-Nyun; Kim, Jae-Won; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

2014-03-01

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Emotionality' and 'Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Proneness to crying' and 'Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration

PubMed Central

Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V.; Glick, Stanley D.; Ron, Dorit

2013-01-01

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action. PMID:21040239

Medicinal plants combating against cancer--a green anticancer approach.

PubMed

Sultana, Sabira; Asif, Hafiz Muhammad; Nazar, Hafiz Muhammad Irfan; Akhtar, Naveed; Rehman, Jalil Ur; Rehman, Riaz Ur

2014-01-01

Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

Differential Patient-Caregiver Opinions of Treatment and Care For Advanced Lung Cancer Patients

PubMed Central

Zyzanski, Stephen J; Siminoff, Laura A

2010-01-01

This study examined the differences of opinion between cancer patients and caregivers with regard to treatment and care decisions. 184 advanced lung cancer patients and 171 primary caregivers were recruited as a convenience sample from clinics in Cleveland, Ohio. A telephone interview was conducted to collect data using a semi-structured questionnaire. Nonparametric tests and regression analysis were performed. The findings showed that patients and caregivers reported significant disagreement on three main issues: trade-off between treatment side effects and benefits; reporting treatment side effects to physicians, and hospice care. Caregivers were more concerned about patient’s quality of life and more willing to discuss hospice issues than were patients. Perceived family disagreement is associated with depression in both patients and caregivers. The study provided empirical evidence for patient-caregiver disagreement about treatment and care decisions and its significant adverse impact on both patients and caregivers. PMID:20137849

Neuroendocrine tumor of cecum in patient treated with imatinib mesylate for blastic phase of chronic myeloid leukemia.

PubMed

Novaković, Sabina; Kovač Peić, Anamarija; Holik, Hrvoje; Coha, Božena

2017-12-01

Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of a NET as a secondary malignancy (SM) after IM treatment. SM have been described in patients on IM before. It is unclear whether these tumors are caused by imatinib or found more easily because of close follow-up.

Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?

PubMed Central

Tan, Eng Chai; Aziz, Noor Azah; Ahmad, Saharuddin

2012-01-01

A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding neuropsychiatric symptoms because they can adversely affect the patient's quality of life as well as impede rehabilitation efforts. PMID:22907854

Intractable epilepsy: management and therapeutic alternatives.

PubMed

Schuele, Stephan U; Lüders, Hans O

2008-06-01

More than half of patients with newly diagnosed epilepsy achieve complete seizure control without major side-effects. Patients who continue to have seizures after initial medical therapy should have an early and detailed assessment to confirm the diagnosis, to determine the underlying cause and epilepsy syndrome, and to choose an adequate treatment strategy. The risks and potential benefits of surgical procedures or experimental therapy have to be weighed against the chance of improvement and the potential side-effects of additional medical therapy. Surgery for temporal lobe epilepsy, the most common cause of focal epilepsy, can control seizures and improve quality of life in appropriately selected patients. However, around 20-30% of patients do not respond to medical or surgical treatment. The management of chronic intractable epilepsy requires comprehensive care to address the adverse events of medical treatment, quality of life issues, and comorbid disorders. Much research focuses on the experimental treatment options that offer hope of seizure reduction or cure.

Tinidazole versus Metronidazole for the Treatment of Bacterial Vaginosis

PubMed Central

SCHWEBKE, Jane R.; DESMOND, Renee A.

2010-01-01

Objective To compare the efficacy of two different doses of tinidazole with metronidazole for treatment of bacterial vaginosis and compare side effects of the drugs. Study design Women were randomized to metronidazole 500 mg BID, tinidazole 500 mg BID, or tinidazole 1 gm BID all for 7 days. Follow-up visits were conducted at day 14 and day 28. Results 593 women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at one month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have BV at follow-up. There were no significant differences in adverse events across treatment arms. Conclusions There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens studied. In addition, there were no important differences in the side effect profiles of metronidazole and tinidazole. PMID:21167471

Pharmacogenomic Challenges in Cardiovascular Diseases: Examples of Drugs and Considerations for Future Integration in Clinical Practice.

PubMed

Chatelin, Jerome; Stathopoulou, Maria G; Arguinano, Alex-Ander A; Xie, Ting; Visvikis-Siest, Sophie

2017-01-01

Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remains the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD. Areas Covered: The complexity of pharmacogenetics and pharmacogenomics of CVD drugs are presented though examples of medications such as statins, with a focus on their effectiveness and adverse effects. Expert Opinion: The application of personalised medicine in the CVD medical practice requires the study of human genome with regard to drugs pharmacokinetics, pharmacodynamics, interactions and tolerance profile. The existing state -of-the-art of CVD drugs gives hopes for a future revolution in the drug development that will maximise cardiovascular patients benefit while decreasing their risks for adverse effects. Article Highlights Box: • Coronary heart disease (CHD) remains the first cause of death worldwide. • Cardiovascular treatment has a significant percentage of insufficient efficacy, poor tolerance and compliance. • Predicting the response to therapy while diminishing the side effects is the basis of personalised medicine; pharmacogenomics is leading towards this direction. • The response to CVD therapy and side effects are in the heart of CVD pharmacogenomics and significant progress has been noted. • The application of pharmacogenomics in the CVD medical practice is facing many methodological, technical, ethical, behavioral and financial issues, while cost-effectiveness is the main prerequisite. • The consideration of gene × gene × environment interactions and the inclusion of "omics" data in pharmacogenomic studies of CVD drugs will facilitate the generation of reliable results and will promote tailored treatments and new strategies of drug research and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthetic cannabinoids: the hidden side of Spice drugs.

PubMed

Pintori, Nicholas; Loi, Barbara; Mereu, Maddalena

2017-09-01

Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs. The absence of validated testing procedures in the clinical field makes difficult the adoption of a therapeutic approach effective in coping with the synthetic cannabinoid phenomenon, posing a significant challenge for prevention, treatment and public health in general. The aim of this review is to gain insights into the epidemiological, pharmacological and toxicological properties of synthetic cannabinoids, aiming to provide a reliable background needed for the management of synthetic cannabinoid-related adverse effects. Consumers, competent authorities and medical care professionals should be aware of the risks associated with synthetic cannabinoid use.

Challenges to Integrating Pharmacogenetic Testing into Medication Therapy Management

PubMed Central

Allen LaPointe, Nancy M.; Moaddeb, Jivan

2015-01-01

Background Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatment(s) to reduce risk of adverse responses and improve efficacy. PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify ineffective and/or harmful drugs or drug combinations. This “enhanced” MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing two key factors that impact patient adherence - concern and necessity. However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined. Objectives In this paper, we consider some of the challenges to the integration and delivery of PGx testing in MTM services. What is already known about this subject While the addition of pharmacogenetic testing has been suggested, little literature exists exploring the challenges or feasibility of doing so. PMID:25803768

Interpretation of Biochemical Tests Using the Reference Change Value in Monitoring Adverse Effects of Oral Isotretinoin in 102 Ethnic Turkish Patients.

PubMed

Bugdayci, Guler; Polat, Mualla; Oguzman, Hamdi; Cinpolat, Havva Yasemin

2016-08-01

The aim of this study was to model the use of reference change values (RCVs) for the follow-up of 4 parameters of patients using oral isotretinoin which is gaining widespread popularity for monitoring the side effects of the treatment. 102 patients received 30 mg/day oral isotretinoin for 24 weeks for the diagnosis of acne vulgaris. Repetitive measurements of the patients were interpreted with RCVs, after comparing the first and second doses based on RCVs: TC, TG, AST and ALT results increased in 12%, 20%, 14% and 12% of the patients respectively. When the first dose was compared with the last dose, the increases were 20%, 29%, 22% and 18% respectively interpreted as significant changes based on laboratory medicine. A more sensitive follow-up is possible in the monitorization of adverse effects by using RCVs method. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

PubMed

Eichstadt, L R; Moore, G E; Childress, M O

2017-12-01

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer. © 2016 John Wiley & Sons Ltd.

Improving platelet transfusion safety: biomedical and technical considerations

PubMed Central

Garraud, Olivier; Cognasse, Fabrice; Tissot, Jean-Daniel; Chavarin, Patricia; Laperche, Syria; Morel, Pascal; Lefrère, Jean-Jacques; Pozzetto, Bruno; Lozano, Miguel; Blumberg, Neil; Osselaer, Jean-Claude

2016-01-01

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the “material” itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing - after years of exhaustive haemovigilance - that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. PMID:26674828

Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

PubMed

Ahern, Terence L; Herring, Andrew A; Miller, Steve; Frazee, Bradley W

2015-07-01

Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events. Wiley Periodicals, Inc.

Underlying Rheumatic Disease: An Important Determinant of Outcome in Tricuspid Valve Repair.

PubMed

Munasur, Mandhir; Naidoo, Datshana

2016-03-01

Tricuspid regurgitation (TR) accompanying severe left-sided valve disease occurs on a functional basis, secondary to pulmonary hypertension and tricuspid annular dilatation. In the context of endemic left-sided rheumatic heart disease, non-recognition of organic disease of the tricuspid valve may adversely influence surgical decision-making, resulting in suboptimal outcomes. A retrospective analysis of the perioperative and follow up data of 30 patients who underwent tricuspid valve surgery with concomitant left-sided valve replacement was undertaken. Preoperative evaluation by two-dimensional transthoracic echocardiography was routinely employed. Outcomes were analyzed by evaluation of the perioperative and two-year follow up clinical and echocardiographic data. All subjects had severe TR. Mixed tricuspid valve disease occurred in 11 subjects (36.7%). Tricuspid valve repair was performed in 28 patients. A significant improvement (p <0.05) in the following parameters occurred at six weeks postoperatively: NYHA functional class, tricuspid annular diameter, systolic pulmonary artery pressure, severity of TR and tricuspid transvalvular gradient. Severe residual postoperative TR occurred in 26.7% of patients, but there were no identifiable predictors for this phenomenon. Severe residual postoperative TR was not associated with major adverse cardiovascular events. Preoperative (p = 0.013) and postoperative (p<0.002) pulmonary hypertension were associated with the development of major adverse cardiovascular events. The technique of tricuspid valve repair was not associated with the occurrence of major adverse cardiovascular events, nor with the development of severe residual postoperative TR. A satisfactory outcome was observed in only 40% of the study population. The coexistence of mixed tricuspid valve disease in rheumatic heart disease patients undergoing left-sided valve surgery is an important determinant of outcome in tricuspid valve repair. The persistence of severe TR contributes to poor long-term outcomes, and its incidence may be lowered by the adoption of appropriate perioperative imaging techniques to delineate valve morphology.

Efficacy of Intense Pulsed Light Therapy in the Treatment of Facial Acne Vulgaris: Comparison of Two Different Fluences

PubMed Central

Patidar, Monika V; Deshmukh, Ashish Ramchandra; Khedkar, Maruti Yadav

2016-01-01

Background: Acne vulgaris is the most common disease of the skin affecting adolescents and young adults causing psychological distress. The combination of antibiotic resistance, adverse effects of topical and systemic anti acne medications and desire for high tech approaches have all led to new enthusiasm for light based acne treatment. Intense pulse light (IPL) therapy has three modes of action in acne vulgaris i.e., photochemical, photo thermal and photo immunological. Aims: (1) to study efficacy of IPL therapy in facial acne vulgaris. (2) To compare two fluences - one normal and other subnormal on right and left side of face respectively. Methods: (Including settings and design and statistical analysis used). Total 45 patients in age group 16 to 28 years with inflammatory facial acne vulgaris were included in prospective study. Baseline data for each patient was recorded. All patients were given 4 sittings of IPL at 2 weeks interval and were followed for 2 months every 2 weeks. Fluence used was 35J/cm2 on right and 20J/cm2 on left side. Percentage reduction in lesion count was calculated at each sitting and follow up and graded as mild (0-25%), moderate (26-50%), good (51-75%) and excellent (76-100%). Side effects were noted. The results were analysed using Mann-Whitney Test. Results: On right side, excellent results were achieved in 10(22%), good in 22(49%) and moderate in 13(29%) patients. On left side excellent were results achieved in 7(15%), good in 19(42%) and moderate in 16(43%) patients. There was no statically significant difference noted in efficacy of two fluences used in treatment of facial acne vulgaris. Conclusions: IPL is a effective and safe option for inflammatory acne vulgaris with minimal reversible side effects. Subnormal fluence is as effective as normal fluence in Indian skin. PMID:27688446

Efficacy of Intense Pulsed Light Therapy in the Treatment of Facial Acne Vulgaris: Comparison of Two Different Fluences.

PubMed

Patidar, Monika V; Deshmukh, Ashish Ramchandra; Khedkar, Maruti Yadav

2016-01-01

Acne vulgaris is the most common disease of the skin affecting adolescents and young adults causing psychological distress. The combination of antibiotic resistance, adverse effects of topical and systemic anti acne medications and desire for high tech approaches have all led to new enthusiasm for light based acne treatment. Intense pulse light (IPL) therapy has three modes of action in acne vulgaris i.e., photochemical, photo thermal and photo immunological. (1) to study efficacy of IPL therapy in facial acne vulgaris. (2) To compare two fluences - one normal and other subnormal on right and left side of face respectively. (Including settings and design and statistical analysis used). Total 45 patients in age group 16 to 28 years with inflammatory facial acne vulgaris were included in prospective study. Baseline data for each patient was recorded. All patients were given 4 sittings of IPL at 2 weeks interval and were followed for 2 months every 2 weeks. Fluence used was 35J/cm(2) on right and 20J/cm(2) on left side. Percentage reduction in lesion count was calculated at each sitting and follow up and graded as mild (0-25%), moderate (26-50%), good (51-75%) and excellent (76-100%). Side effects were noted. The results were analysed using Mann-Whitney Test. On right side, excellent results were achieved in 10(22%), good in 22(49%) and moderate in 13(29%) patients. On left side excellent were results achieved in 7(15%), good in 19(42%) and moderate in 16(43%) patients. There was no statically significant difference noted in efficacy of two fluences used in treatment of facial acne vulgaris. IPL is a effective and safe option for inflammatory acne vulgaris with minimal reversible side effects. Subnormal fluence is as effective as normal fluence in Indian skin.

A case of vemurafenib-induced polyarhritis in a patient with melanoma: how to manage it?

PubMed

Babacan, Taner; Türkbeyler, Ibrahim Halil; Balakan, Ozan; Pehlivan, Yavuz; Suner, Ali; Kısacık, Bunyamin

2017-03-01

Vemurafenib is an inhibitor of the BRAF V600E mutation which is associated with tumor responses in patients with metastatic melanoma. Although it is generally well tolerated, common side effects of vemurafenib have been reported. Arthralgia is one of the more common adverse event associated with vemurafenib. We herein report a 49-year-old woman diagnosed with metastatic melanoma harboring the BRAF V600E mutation with severe polyarthritis associated with vemurafenib after 7 days of treatment. Sonographic examination of affected joints revealed synovitis and the patient's articular symptoms were improved by analgesic and anti-inflammatory treatment, including corticosteroids. During therapy with selective BRAF inhibitors, arthritis represents a new adverse event that can require dose reduction. In case of this adverse event, treatment with anti-inflammatory drugs, such as ibuprofen and prednisone, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Impact of physical exercise in cancer survivors during and after antineoplastic treatments

PubMed Central

Ferioli, Martina; Zauli, Giorgio; Martelli, Alberto M.; Vitale, Marco; McCubrey, James A.; Ultimo, Simona; Capitani, Silvano; Neri, Luca M.

2018-01-01

Cancer patients experience symptoms and adverse effects of treatments that may last even after the end of treatments. Exercise is a safe, non-pharmacological and cost-effective therapy that can provide several health benefits in cancer patient and survivors, reducing cancer symptoms and cancer treatment side effects. The purpose of this review is to describe how the physical exercise is capable to reduce cancer symptoms and cancer treatment side effects. We realized a pragmatic classification of symptoms, dividing them into physical, psychological and psycho-physical aspects. For each symptom we discuss causes, therapies, we analyse the effects of physical exercise and we summarize the most effective type of exercise to reduce the symptoms. This review also points out what are the difficulties that patients and survivors face during the practice of physical activity and provides some solutions to overcome these barriers. Related to each specific cancer, it emerges that type, frequency and intensity of physical exercise could be prescribed and supervised as a therapeutic program, like it occurs for the type, dose and duration of a drug treatment. PMID:29568412

Adverse reactions of trivalent influenza vaccine in HIV-infected individuals.

PubMed

Hajiabdolbaghi, Mahboube; Jam, Sara; SeyedAlinaghi, SeyedAhmad; Jafari, Sirous; Badie, Banafshe Moradmand; Sabzvari, Duman

2010-01-01

In this study, we assessed the adverse reactions to influenza vaccination in HIV-infected individuals. From November 2006 to January 2007, a total of 203 HIV-infected persons were recruited. Demographic data were collected. Subjects were evaluated 48 h and 15 days after vaccination for symptoms and significant health events as possible side effects. Participants were instructed to measure their temperature in the morning and evening for 2 days post-immunization and to assess injection site and systemic adverse reactions. 80.3% of the subjects were male. The mean age of the subjects was 36.9 +/- 7.9 years. Local and systemic reactions were reported by 61 (30%) and 62 (30.5%) persons, respectively. The most common adverse reactions to the influenza vaccine included skin redness (37 cases), induration (32 cases), and pain (55 cases) as local reactions, and fever (22 cases), myalgia (46 cases), headache (12 cases) and weakness (35 cases) as general reactions. 1.4 % of the subjects had fever over 38.5 degrees C. There were significant associations between myalgia and flushing with CD4 counts (P<0.05). We found no relationship between adverse reactions and sex, history of smoking, allergy, alcohol, and drug usage, stage of HIV infection, anti-retroviral therapies, anti-TB medication and previous vaccination. We concluded that inactivated influenza vaccine administered in HIV-infected adults did not result in potential adverse events in this study population.

Splenic trauma as an adverse effect of torso-protecting side airbags: biomechanical and case evidence.

PubMed

Hallman, Jason J; Brasel, Karen J; Yoganandan, Narayan; Pintar, Frank A

2009-10-01

Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis.

Splenic Trauma as an Adverse Effect of Torso-Protecting Side Airbags: Biomechanical and Case Evidence

PubMed Central

Hallman, Jason J.; Brasel, Karen J.; Yoganandan, Narayan; Pintar, Frank A.

2009-01-01

Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis. PMID:20184829

Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.

PubMed

Kashani, Ladan; Esalatmanesh, Sophia; Eftekhari, Farzaneh; Salimi, Samrand; Foroughifar, Tahereh; Etesam, Farnaz; Safiaghdam, Hamideh; Moazen-Zadeh, Ehsan; Akhondzadeh, Shahin

2018-03-01

Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes. Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study. Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly different between the two groups. Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.

Toxicity of bioactive and probiotic marine bacteria and their secondary metabolites in Artemia sp. and Caenorhabditis elegans as eukaryotic model organisms.

PubMed

Neu, Anna Katrin; Månsson, Maria; Gram, Lone; Prol-García, María J

2014-01-01

We have previously reported that some strains belonging to the marine Actinobacteria class, the Pseudoalteromonas genus, the Roseobacter clade, and the Photobacteriaceae and Vibrionaceae families produce both antibacterial and antivirulence compounds, and these organisms are interesting from an applied point of view as fish probiotics or as a source of pharmaceutical compounds. The application of either organisms or compounds requires that they do not cause any side effects, such as toxicity in eukaryotic organisms. The purpose of this study was to determine whether these bacteria or their compounds have any toxic side effects in the eukaryotic organisms Artemia sp. and Caenorhabditis elegans. Arthrobacter davidanieli WX-11, Pseudoalteromonas luteoviolacea S4060, P. piscicida S2049, P. rubra S2471, Photobacterium halotolerans S2753, and Vibrio coralliilyticus S2052 were lethal to either or both model eukaryotes. The toxicity of P. luteoviolacea S4060 could be related to the production of the antibacterial compound pentabromopseudilin, while the adverse effect observed in the presence of P. halotolerans S2753 and V. coralliilyticus S2052 could not be explained by the production of holomycin nor andrimid, the respective antibiotic compounds in these organisms. In contrast, the tropodithietic acid (TDA)-producing bacteria Phaeobacter inhibens DSM17395 and Ruegeria mobilis F1926 and TDA itself had no adverse effect on the target organisms. These results reaffirm TDA-producing Roseobacter bacteria as a promising group to be used as probiotics in aquaculture, whereas Actinobacteria, Pseudoalteromonas, Photobacteriaceae, and Vibrionaceae should be used with caution.

Toxicity of Bioactive and Probiotic Marine Bacteria and Their Secondary Metabolites in Artemia sp. and Caenorhabditis elegans as Eukaryotic Model Organisms

PubMed Central

Neu, Anna Katrin; Månsson, Maria; Prol-García, María J.

2014-01-01

We have previously reported that some strains belonging to the marine Actinobacteria class, the Pseudoalteromonas genus, the Roseobacter clade, and the Photobacteriaceae and Vibrionaceae families produce both antibacterial and antivirulence compounds, and these organisms are interesting from an applied point of view as fish probiotics or as a source of pharmaceutical compounds. The application of either organisms or compounds requires that they do not cause any side effects, such as toxicity in eukaryotic organisms. The purpose of this study was to determine whether these bacteria or their compounds have any toxic side effects in the eukaryotic organisms Artemia sp. and Caenorhabditis elegans. Arthrobacter davidanieli WX-11, Pseudoalteromonas luteoviolacea S4060, P. piscicida S2049, P. rubra S2471, Photobacterium halotolerans S2753, and Vibrio coralliilyticus S2052 were lethal to either or both model eukaryotes. The toxicity of P. luteoviolacea S4060 could be related to the production of the antibacterial compound pentabromopseudilin, while the adverse effect observed in the presence of P. halotolerans S2753 and V. coralliilyticus S2052 could not be explained by the production of holomycin nor andrimid, the respective antibiotic compounds in these organisms. In contrast, the tropodithietic acid (TDA)-producing bacteria Phaeobacter inhibens DSM17395 and Ruegeria mobilis F1926 and TDA itself had no adverse effect on the target organisms. These results reaffirm TDA-producing Roseobacter bacteria as a promising group to be used as probiotics in aquaculture, whereas Actinobacteria, Pseudoalteromonas, Photobacteriaceae, and Vibrionaceae should be used with caution. PMID:24141121

Efficacy of topical azathioprine and betamethasone versus betamethasone-only emollient cream in 2-18 years old patients with moderate-to-severe atopic dermatitis: A randomized controlled trial

PubMed Central

Iraji, Fariba; Farhadi, Sadaf; Faghihi, Gita; Mokhtari, Fatemeh; Basiri, Akram; Jafari-Koshki, Tohid; Nilforoushzadeh, Mohammad Ali

2015-01-01

Background: Atopic dermatitis is a chronic skin disease with increasing prevalence worldwide and a considerable burden especially among children. To circumvent the problems related to oral azathioprine (AZT) we aimed to evaluate its topical variant and assess its efficacy in patients aged 2–18. Materials and Methods: In a single-blind trial, we randomized the patients into two groups, one treated with topical emollient containing AZT and betamethasone (BM), and the other treated solely with topical emollient of BM. The treatments were administered twice a day for 8 weeks in both groups. The efficacy, recurrence, and the presence of side effects were evaluated using SPSS 20. Results: The amount of reduction in severity scoring for atopic dermatitis (SCORAD) score was significantly greater in the group treated with the topical AZT (P = 0.024). Incidentally, there were no difference between two treatments in difference in proportions of recurrence and adverse effects as well as SCORAD reduction in subgroups of sex and age (all P > 0.05). Conclusions: Our results showed the superiority of topical AZT over BM with a low recurrence and adverse effects. No expectation of severe side effects, like those of oral AZT, is the major advantage of topical AZT. The sample size was an issue in uncovering the value of AZT in the subgroups. Conducting prolonged studies of quality-of-life and comparing the topical AZT potency relative to the common alternatives are recommended areas of future work. PMID:26623403

Impact Factors Analysis of the Hot Side Temperature of Thermoelectric Module

NASA Astrophysics Data System (ADS)

Zhang, Xingyu; Tan, Gangfeng; Yang, Bo

2018-03-01

The thermoelectric generator (TEG) plays a crucial role in converting the waste energy of exhaust into electricity, which ensures energy saving and increased fuel utilization efficiency. In the urban driving cycle, frequent vehicle operation, like deceleration or acceleration, results in continuous variation of the exhaust temperature. In order to make the operating performance stable, and to weaken the adverse effects of the frequent variation of the exhaust temperature on the lifetime and work efficiency of the electronic components of TEG systems, the output voltage of the thermoelectric (TE) module should stay more stable. This article provides an improved method for the temperature stability of the TE material hot side based on sandwiching material. From the view of the TEG system's average output power and the hot side temperature stability of the TE material, the analyzing factors, including the fluctuation frequency of the exhaust temperature and the physical properties and thickness of the sandwiching material are evaluated, respectively, in the sine and new European driving cycle (NEDC) fluctuation condition of the exhaust temperature. The results show few effects of sandwiching material thickness with excellent thermal conductivity on the average output power. During the 150-170 s of the NEDC test condition, the minimum hot side temperatures with a BeO ceramic thickness of 2 mm and 6 mm are, respectively, 537.19 K and 685.70 K, which shows the obvious effect on the hot side temperature stability of the BeO ceramic thickness in the process of acceleration and deceleration of vehicle driving.

Impact Factors Analysis of the Hot Side Temperature of Thermoelectric Module

NASA Astrophysics Data System (ADS)

Zhang, Xingyu; Tan, Gangfeng; Yang, Bo

2017-12-01

The thermoelectric generator (TEG) plays a crucial role in converting the waste energy of exhaust into electricity, which ensures energy saving and increased fuel utilization efficiency. In the urban driving cycle, frequent vehicle operation, like deceleration or acceleration, results in continuous variation of the exhaust temperature. In order to make the operating performance stable, and to weaken the adverse effects of the frequent variation of the exhaust temperature on the lifetime and work efficiency of the electronic components of TEG systems, the output voltage of the thermoelectric (TE) module should stay more stable. This article provides an improved method for the temperature stability of the TE material hot side based on sandwiching material. From the view of the TEG system's average output power and the hot side temperature stability of the TE material, the analyzing factors, including the fluctuation frequency of the exhaust temperature and the physical properties and thickness of the sandwiching material are evaluated, respectively, in the sine and new European driving cycle (NEDC) fluctuation condition of the exhaust temperature. The results show few effects of sandwiching material thickness with excellent thermal conductivity on the average output power. During the 150-170 s of the NEDC test condition, the minimum hot side temperatures with a BeO ceramic thickness of 2 mm and 6 mm are, respectively, 537.19 K and 685.70 K, which shows the obvious effect on the hot side temperature stability of the BeO ceramic thickness in the process of acceleration and deceleration of vehicle driving.

Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells.

PubMed

Kim, Jeong Hwan; Jeong, Soo-Jin; Kwon, Hee-Young; Park, Sang Yoon; Lee, Hyo-Jung; Lee, Hyo-Jeong; Lieske, John Charles; Kim, Sung-Hoon

2010-01-01

Adverse effects, nephrotoxicity and hepatotoxicity, of anticancer drugs such as cisplatin have limited the usage for cancer therapy. Therefore, development or identification of supplement agents in anticancer drugs is attractive to reduce side effects and enhance antitumor activity. Here, we found that decursin isolated from Angelica gigas showed protective effects of cisplatin-induced damage in normal human primary renal epithelial cells (HRCs). We found that decursin significantly blocked cisplatin-induced cytotoxicity by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HRCs. Further, we found that decursin inhibited sub-G1 and cell death by suppression of cleavage of caspase-3, -9 and poly(ADP-ribose) polymerase (PARP) induced by cisplatin treatment in HRCs. Importantly, decursin effectively restored the activities of Cu/Zn superoxide dismutase (SOD), catalase and glutathione peroxidase in cisplatin-treated HRCs. Taken together, our findings demonstrate that decurcin prevents cisplatin-induced cytotoxicity and apoptosis through the activation of antioxidant enzymes in HRCs and suggest further that combination of decursin might suppressed adverse effects of anticancer drugs in cancer patients.

Safety of antiobesity drugs

PubMed Central

Cheung, Tommy Tsang; Samaranayake, Nithushi Rajitha

2013-01-01

Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn. Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves. Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of significant psychiatric adverse effects. Orlistat was approved in Europe and the United States for long-term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects. Phentermine and diethylpropion can only be used for less than 12 weeks because the long-term safety of these drugs is unknown. Ephedrine and caffeine are natural substances but the effects on weight reduction are modest. As a result there is a huge unmet need for effective and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long-term safety data are lacking. PMID:25114779

Safety of antimalarial medications for use while scuba diving in malaria Endemic Regions.

PubMed

Petersen, Kyle; Regis, David P

2016-01-01

Recreational diving occurs annually in areas of the world where malaria is endemic. The safety and efficacy of antimalarials for travelers in a hyperbaric environment is unknown. Of particular concern would be medications with adverse effects that could either mimic diving related illnesses such as barotrauma, decompression sickness (DCS) and gas toxicities, or increase the risk for such illnesses. We conducted a review of PubMed and Cochrane databases to determine rates of neurologic adverse effects or other effects from antimalarials that may be a problem in the diving environment. One case report was found on diving and mefloquine. Multiple case reports and clinical trials were found describing neurologic adverse effects of the major chemoprophylactic medications atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine. Of the available literature, atovaquone/proguanil and doxycycline are most likely the safest agents and should be preferred; atovaquone/proguanil is superior due to reduced rates of sunburn in the marine environment. Primaquine also appears to be safe, but has reduced efficacy against P. falciparum ; mefloquine possesses the highest rate of neurologic side effects and therefore these agents should be limited to extreme cases of patients intolerant to other agents. Chloroquine appears unsafe in the hyperbaric environment and should be avoided. More studies are required to include database reviews of returned divers traveling to malaria endemic areas and randomized controlled trials in the hyperbaric environments.

Orthodontic space closure without contralateral extraction through mesial movement of lower molars in patients with aplastic lower second premolars.

PubMed

Zimmer, B; Guitard, Y

2001-09-01

A method is presented that allows unilateral space closure in patients with aplastic lower second premolars. Based on a straight-wire appliance, space closure was achieved with a combination of "push mechanics" using the second molar as an anchorage unit and Class II "pull mechanics", thus avoiding the application of any distalizing force on the lower incisors. The results from 13 consecutively treated subjects (five boys, eight girls, mean age 12 years and 6 months) were analyzed. Complete bodily space closure was achieved in all 13 cases within a mean treatment time of 2 years and 7 months. The desired Angle Class III molar relationship of one premolar width (+/- 1/4 premolar width) on the aplastic side was successful in eleven patients, an additional 4.7 mm of space being created for the third molar on the aplastic side compared with the contralateral side (p < or = 0.01). However, adverse effects could be kept to a minimum, with no method-dependent side effects being recorded with regard to canine and molar relationships on the contralateral side, or to overbite, overjet, or upper and lower incisor inclination. The mean lower midline shift of 0.8 mm was in accordance with the mean distal canine relationship of 1/3 premolar width on the aplastic side. These results confirm that orthodontic space closure in cases of unilateral aplastic lower second premolars can be performed successfully with the presented treatment method without the need for additional premolar extractions, prosthodontic treatment or implants. Furthermore, the prognosis for the lower wisdom tooth on the aplastic side is improved.

Treatment of molluscum contagiosum with an East Indian sandalwood oil product.

PubMed

Haque, Malika; Coury, Daniel L

2017-11-22

To evaluate the safety and efficacy of an East Indian sandalwood oil (EISO) product as a topical treatment for molluscum contagiosum. Ten subjects ranging in age from 22 months to 29 years were recruited. Subjects were instructed to apply an EISO product to the lesions twice daily. Subjects were monitored every two to three weeks during the study and were questioned regarding local or systemic side effects. Assessment of response was recorded by counting lesions and documented by photographs. Nine of ten subjects (90%) experienced complete resolution of molluscum lesions within the twelve week study period. Response was unrelated to lesion size or number, how long the molluscum rash had been present, or patient age or gender. There were no complaints of side effects, skin irritation, pain, or other adverse events reported in any subjects. In this pilot open label study, an EISO product proved to be an effective treatment for molluscum contagiosum lesions with resolution of lesions typically occurring within twelve weeks of therapy.

[Vedolizumab (Entyvio®) for the treatment of inflammatory bowel diseases].

PubMed

Van Kemseke, C; Louis, E; Reenaers, C

2015-11-01

Anti-TNF agents are highly effective in treating inflammatory bowel diseases, but loss of response and side-effects leading to drug interruption are often reported. New molecules are needed to treat these patients. Vedolizumab is a fully humanized anti-body inhibiting the migration of circulating lymphocytes to the gut by binding the integrin α4β7. In ulcerative colitis, clinical response, remission and mucosal healing were observed at 6 weeks in 47%, 17% and 40% of the patients, respectively. The maintenance study demonstrated 42% and 52% of clinical remission and response at week 52. In Crohn's disease, clinical response and remission were respectively observed in 15% and 31% of the patients at 6 weeks. Clinical remission at week 52 was 39%. The time to clinical response was longer in patients who had failed anti-TNF. The safety profile is excellent with the same proportion of side-effects in the placebo and in the treated groups. The most frequently reported adverse events were pharyngitis and headaches.

[Analysis of after-vacination side-effects occurred in Teresina].

PubMed

de Araújo, Telma Maria Evangelista; de Carvalho, Patrícia Maria Gomes; Vieira, Raimunda Damasceno Ferreira

2007-01-01

This study focuses the profile of the adverse events after-vaccine occurrences in Teresina in 2006. The data had been collected by means of the form application with 73 participants in 18 Basic Units of Health. The results show that the vaccines that had more produced events adverse had been tetravalente, BCG and DPT The events most frequent had been: fever, hiporresponsivo hipotonic episode, moderate irritability and local manifestations. Amongst the behaviors adopted for the health professionals, 80% had been approximately adjusted. The year minors had been accomitted by the events. All the events had evolved for the cure. It was concluded that the action of vaccination still continues requiring constant qualification of the professionals of the area. It is suggested to deepen the knowledge with relation to the handling, diagnosis, inquiry and treatment.

Association of Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium

PubMed Central

Ito, Tetsuhide; Jensen, Robert T.

2010-01-01

Proton pump inhibitors (PPI) are now one of the most widely used classes of drugs. PPIs have proven to have a very favorable safety profile and it is unusual for a patient to stop these drugs because of side effects. However, increasing numbers of patients are chronically taking PPIs for gastroesophageal reflux disease and a number of other common persistent conditions, therefore the long-term potential adverse effects are receiving increasing attention. One area that is receiving much attention and generally has been poorly studied, is the long-term effects of chronic acid suppression on the absorption of vitamins and nutrients. This area has received increased attention because of the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. This has led to an increased examination of the effects of PPIs on calcium absorption/metabolism as well as numerous cohort, case control and prospective studies of their ability to affect bone density and cause bone fractures. In this article these studies are systematically examined, as well as the studies of the effects of chronic PPI usage on VB12, iron and magnesium absorption. In general the studies in each of thee areas have led to differing conclusions, but when examined systematically, a number of the studies are showing consistent results that support the conclusion that long-term adverse effects on these processes can have important clinical implications. PMID:20882439

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

PubMed

Chen, Shu-Huey; Yang, Shang-Hsien; Chu, Sung-Chao; Su, Yu-Chieh; Chang, Chu-Yu; Chiu, Ya-Wen; Kao, Ruey-Ho; Li, Dian-Kun; Yang, Kuo-Liang; Wang, Tso-Fu

2011-05-01

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/μL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/μL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 μg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

Skin Color, Cultural Capital, and Beauty Products: An Investigation of the Use of Skin Fairness Products in Mumbai, India

PubMed Central

Shroff, Hemal; Diedrichs, Phillippa C.; Craddock, Nadia

2018-01-01

The use of skin fairness products that frequently contain toxic ingredients is associated with significant adverse health side effects. Due to the high prevalence of use in Asian and African countries, skin fairness product use is recognized as a growing public health concern. The multi-million-dollar skin fairness product industry has also been criticized for perpetuating racism and social inequalities by reinforcing beliefs about the benefits of skin fairness for cultural capital. No quantitative studies have assessed people’s beliefs about fairness and reasons for using or not using these products in India, one of the largest global markets for skin fairness products. The current study explored skin fairness product use among 1,992 women and men aged 16–60 years in the city of Mumbai, India using a self-report questionnaire. A total of 37.6% of the sample reported currently using skin fairness products, with women being two times more likely to use these products. Among current users, 17% reported past experiences of adverse side effects, and “Media/TV/Adverts” were the most common prompts for using fairness products, followed by “Friends” and “Family.” Men were significantly more likely than women to endorse beliefs about fairness being more attractive and were more likely to perceive family and peers as viewing fairness as beneficial for cultural capital. There were no differences between women and men currently using products in their desire to look as fair as media celebrities. Among non-users, women were significantly more likely than men to report concerns about product efficacy and side effects as reasons for non-use, while men were significantly more likely to report socioeconomic reasons for non-use. Implications of these findings are discussed in light of growing public health concerns about the use of fairness products, and potential for advocacy and public health interventions to address the use of skin fairness products. PMID:29410952

[Pharmacovigilance center --internal medicine interactions: A useful diagnostic tool].

PubMed

Rochoy, M; Gautier, S; Bordet, R; Caron, J; Launay, D; Hachulla, E; Hatron, P-Y; Lambert, M

2015-08-01

Patients hospitalized in internal medicine often have unexplained clinical symptoms for which a drug origin can be considered. The prevalence of patients hospitalized for iatrogenic is estimated between 4-22%. We wanted to evaluate the diagnostic value of the regional center of pharmacovigilance to identify or confirm an iatrogenic disease in the department of internal medicine of Lille and characterize factors associated with drug-related side effect. This is a single-center prospective diagnostic study. We included all subsequent requests from the department of internal medicine with the Nord-Pas-de-Calais regional pharmacovigilance center between 2010 and 2012. The opinion of the regional pharmacovigilance centre was held on the record of the adverse drug reaction in the national pharmacovigilance database and analyzed according to the conclusion of iatrogenic used by clinicians in internal medicine (reference diagnosis) with a follow-up to June 2013. The variables relating to the patient, medication and adverse events were analyzed by binary logistic regression. We analyzed 160 contacts: 118 concordant cases, 38 false-positives (drug-related side effect retained by the regional pharmacovigilance center only), 4 false negatives. Registration in the national pharmacovigilance database had a sensitivity of 96% (95% CI [0.92 to 0.99]), a specificity of 46% (95% CI [0.38 to 0.53]), a value positive predictive of 69% (95% CI [0.62 to 0.76]), a negative predictive value of 89% (95% CI [0.84 to 0.94]) and a negative likelihood ratio of 0.1. False-positive had chronological and semiological accountabilities questionable (adjusted RR=2.1, 95% CI [1.2 to 2.8]). In our study, the regional pharmacovigilance center confirms the clinician's suspicion of drug-related side effects and helps to exclude drug-induced with a high negative predictive value. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Skin Color, Cultural Capital, and Beauty Products: An Investigation of the Use of Skin Fairness Products in Mumbai, India.

PubMed

Shroff, Hemal; Diedrichs, Phillippa C; Craddock, Nadia

2017-01-01

The use of skin fairness products that frequently contain toxic ingredients is associated with significant adverse health side effects. Due to the high prevalence of use in Asian and African countries, skin fairness product use is recognized as a growing public health concern. The multi-million-dollar skin fairness product industry has also been criticized for perpetuating racism and social inequalities by reinforcing beliefs about the benefits of skin fairness for cultural capital. No quantitative studies have assessed people's beliefs about fairness and reasons for using or not using these products in India, one of the largest global markets for skin fairness products. The current study explored skin fairness product use among 1,992 women and men aged 16-60 years in the city of Mumbai, India using a self-report questionnaire. A total of 37.6% of the sample reported currently using skin fairness products, with women being two times more likely to use these products. Among current users, 17% reported past experiences of adverse side effects, and "Media/TV/Adverts" were the most common prompts for using fairness products, followed by "Friends" and "Family." Men were significantly more likely than women to endorse beliefs about fairness being more attractive and were more likely to perceive family and peers as viewing fairness as beneficial for cultural capital. There were no differences between women and men currently using products in their desire to look as fair as media celebrities. Among non-users, women were significantly more likely than men to report concerns about product efficacy and side effects as reasons for non-use, while men were significantly more likely to report socioeconomic reasons for non-use. Implications of these findings are discussed in light of growing public health concerns about the use of fairness products, and potential for advocacy and public health interventions to address the use of skin fairness products.

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

PubMed Central

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

2016-01-01

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

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

PubMed

Badawi, Alaa; Shering, Maria; Rahman, Shusmita; Lindsay, L Robbin

2017-04-20

Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p < 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 μg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p < 0.001). The current study further validates that the monovalent and multivalent LB vaccines result in mild local side effects and self-limiting systemic adverse effects, with the multivalent vaccine slightly more tolerable than the monovalent one. Both vaccine classes were similarly highly immunogenic. A new vaccine with high safety standards, better efficacy, low cost, and public acceptance is yet to be developed. Meanwhile, personal protection limiting exposure to ticks is recommended.

Imipenem-cilastatin-induced psychosis: a case report.

PubMed

Ninan, Jacob; George, Gemy Maria

2016-04-27

Elderly patients, in particular, have been reported to develop psychiatric side effects from antibiotics. Clarithromycin, quinolones, sulfamethoxazole-trimethoprim, isoniazid, penicillin, and cephalosporins have been reported to cause psychosis. This case report bridges a void in the medical literature with regards to the psychiatric adverse effects of imipenem-cilastatin. A 64-year-old Hispanic man in septic shock due to urinary tract infection was initiated on imipenem-cilastatin and mechanically ventilated, following admission to hospital. His mentation was normal for 72 hours after extubation and discontinuation of sedatives and opioids, following which he was noted to be in acute psychosis. Our patient's imipenem-cilastatin dose had been increased 24 hours prior to his violent visual and auditory hallucinations because his renal function had improved. The physical examination and laboratory tests did not reveal evidence of a new central nervous infection or endocrinopathy. His mentation improved after his antibiotic was switched to ceftriaxone, based on culture and sensitivity testing. Similar psychiatric symptoms developed 2 months later when he was treated with imipenem for a recurrent urinary tract infection. His symptoms again resolved with modification of his antibiotic regimen. Endocrine dysfunctions (thyroid, adrenal, and pituitary disorders) and toxic ingestions are medical disorders known to cause brief psychotic episodes. Fluoroquinolones, penicillins, and trimethoprim-sulfamethoxazole are common antibiotics associated with this rare adverse effect. Several pharmacokinetic hypotheses have been proposed for this adverse effect: (1) N-methyl-D-aspartate receptor hypofunctioning, (2) sequential blockade of folic acid production, (3) inhibition of prostaglandin E2 and proinflammatory cytokine production, (4) increased central dopamine turnover, and (5) accumulation of toxic levels of the drug. Pre-existing psychopathology, relevant comorbidities, slow acetylation status, and increased permeability of the blood-brain barrier have been suggested to make patients more prone to developing psychosis. According to the literature, this psychiatric manifestation resolves within 2 weeks of discontinuing the offending agent. There appears to be underreporting of the psychiatric manifestations of imipenem-cilastatin, contrary to post-marketing surveillance data. It is imperative that physicians recognize these psychiatric side effects of antibiotics, because they are a fundamental treatment option.

Hypothyroidism Side Effect in Patients Treated with Sunitinib or Sorafenib: Clinical and Structural Analyses

PubMed Central

Shu, Mao; Zai, Xiaoli; Zhang, Beina; Wang, Rui; Lin, Zhihua

2016-01-01

Tyrosine kinase inhibitors (TKIs) provide more effective targeted treatments for cancer, but are subject to a variety of adverse effects, such as hypothyroidism. TKI-induced hypothyroidism is a highly complicated issue, because of not only the unrealized toxicological mechanisms, but also different incidences of individual TKI drugs. While sunitinib is suspected for causing thyroid dysfunction more often than other TKIs, sorafenib is believed to be less risky. Here we integrated clinical data and in silico drug-protein interactions to examine the pharmacological distinction between sunitinib and sorafenib. Statistical analysis on the FDA Adverse Event Reporting System (FAERS) confirmed that sunitinib is more concurrent with hypothyroidism than sorafenib, which was observed in both female and male patients. Then, we used docking method and identified 3 proteins specifically binding to sunitinib but not sorafenib, i.e., retinoid X receptor alpha, retinoic acid receptors beta and gamma. As potential off-targets of sunitinib, these proteins are well known to assemble with thyroid hormone receptors, which can explain the profound impact of sunitinib on thyroid function. Taken together, we established a strategy of integrated analysis on clinical records and drug off-targets, which can be applied to explore the molecular basis of various adverse drug reactions. PMID:26784451

Humic Acids as Therapeutic Compounds in Lead Intoxication.

PubMed

Krempaská, Klára; Vaško, Ladislav; Vašková, Janka

2016-01-01

The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

Efficacy and safety of oral baclofen in the management of spasticity: A rationale for intrathecal baclofen.

PubMed

Ertzgaard, Per; Campo, Claudia; Calabrese, Alessandra

2017-03-06

Oral baclofen has long been a mainstay in the management of spasticity. This review looks at the clinical evidence for the efficacy and safety of oral baclofen in patients with spasticity of any origin or severity, to determine whether there is a rationale for the use of intrathecal baclofen. Results suggest that oral baclofen may be effective in many patients with spasticity, regardless of the underlying disease or severity, and that it is at least comparable with other antispasmodic agents. However, adverse effects, such as muscle weakness, nausea, somnolence and paraesthesia, are common with oral baclofen, affecting between 25% and 75% of patients, and limiting its usefulness. Intrathecal baclofen may be an effective alternative as the drug is delivered directly into the cerebrospinal fluid, thus bypassing the blood-brain barrier and thereby optimizing the efficacy of baclofen while minimizing drug-related side-effects. Intrathecal baclofen is a viable option in patients who experience intolerable side-effects or who fail to respond to the maximum recommended dose of oral baclofen.

Phytochemicals and PI3K Inhibitors in Cancer—An Insight

PubMed Central

Suvarna, Vasanti; Murahari, Manikanta; Khan, Tabassum; Chaubey, Pramila; Sangave, Preeti

2017-01-01

In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies are expensive and are associated with adverse side effects. Thus, considering the current status of cancer treatment there is scope to search for efficient therapies which are cost-effective and are associated with lesser and milder side effects. Phytochemicals have been utilized for many decades to prevent and cure various ailments and current evidences indicate use of phytochemicals as an effective treatment for cancer. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling cascades is a common phenomenon in most types of cancers. Thus, natural substances targeting PI3K pathway can be of great therapeutic potential in the treatment of cancer patients. This chapter summarizes the updated research on plant-derived substances targeting PI3K pathway and the current status of their preclinical studies and clinical trials. PMID:29311925

Outcome of cancer-related seizures in patients treated with lacosamide.

PubMed

Toledo, M; Molins, A; Quintana, M; Santamarina, E; Martinez-Ricarte, F; Martínez-Saez, E; Salas-Puig, J

2018-01-01

Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events. Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of NSAIDs in triathletes: prevalence, level of awareness and reasons for use.

PubMed

Gorski, T; Cadore, E Lusa; Pinto, S Santana; da Silva, E Marczwski; Correa, C Silva; Beltrami, F Gabe; Kruel, L F Martins

2011-02-01

to determine the level of awareness regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and the prevalence and reasons for their consumption among athletes competing at the 2008 Brazil Ironman Triathlon (3.8 km swim, 180 km cycle and 42.2 km run). survey study. 2008 Brazil Ironman Triathlon, Florianópolis, Brazil, May 2008. 327 Of the 1250 athletes competing at the 2008 Brazil Ironman Triathlon were enrolled in the study. athletes answered a questionnaire about NSAID effects, side effects and consumption at the bike checkout or awards lunch. 196 (59.9%) Athletes reported using NSAIDs in the previous 3 months; of these, 25.5% (n=50), 17.9% (n=35) and 47.4% (n=93) consumed NSAIDs the day before, immediately before and during the race, respectively. Among NSAID users, 48.5% (n=95) consumed them without medical prescription. The main reason given for NSAID consumption in the previous 3 months was the treatment of injuries, while the main reason given for consuming NSAIDs during the race was pain prevention. Despite anti-inflammatory and analgesic effects, most athletes were unaware of the effects of NSAIDs, and the only adverse effects known by most athletes were the gastrointestinal complications. this study found a high prevalence of NSAID consumption, limited awareness of the effects and side effects of them and a high rate of nonprescribed use. It is suggested that long-distance triathlon events include in their programmes educational devices such as talks or folders about NSAID use, effects and side effects.

World apheresis registry report.

PubMed

Stegmayr, Bernd; Ptak, Jan; Wikström, Björn

2007-02-01

The establishment of national apheresis registries has been helpful to learn about therapeutic profiles and adverse event incidences. During 2003, the World Apheresis Registry was established and centers from all countries were invited to participate to register their apheresis activities (at www.iml.umu.se/medicin). In this paper, we will report and analyze the first data retrieved from three centers, in 2 European countries, that registered a total of 388 therapeutic apheresis treatments in 122 patients, 95% due to acute indications. Statistical analyses were performed using an independent Student t-test and Fisher's test. A p-value of less than 0.05 was considered significant. Fifty percent of the treated patients were women. The mean age of the patients was 51 years (+/-17, range 16-84) and there was no difference between genders (w 50.4, m 51.6 years). Diagnoses for treatment were mainly neurological and vasculitis. In 63% peripheral access was used with a central double lumen catheter, 22% in the jugular vein, 8% in the subclavian vein and 6% the femoral vein. Significant inter-center differences were seen in regard to the access used. The main technique used was centrifugation for conventional plasma exchange (86%), while other modes were leukapheresis, erythrapheresis, platelet apheresis, LDL-apheresis and adsorption of antibodies. Citrate was the only anticoagulant in 92%. During plasma exchange procedures using centrifugation, replacement was by albumin only (58%) or plasma, the latter often in combination with albumin (42%). Adverse events (AEs) were noted in 11% of the procedures. Patients with hypocalcaemia side effects with tingling sensations were included in those data as mild AE and as moderate AEs if they received calcium (Ca) medication. No patient died due to adverse effects. A mild AE was present in 1.8% and moderate in 8.5%. During two procedures (0.5%), the AE was considered severe and therefore the procedure was interrupted. If those with AEs due to lower calcium were removed from analyses, 6.4% had AEs. Significantly more AEs were found when plasma was used as a replacement fluid (p=0.017, RR 2.05, CI 1.17-3.60). There were no differences in the incidence of AEs between genders. The number of procedures was too small to allow sub analyses of AEs in relation to the diagnoses. Adverse events were not related to the procedure used (p=0.095). Those who received additional Ca infusion during the procedure had no AEs (40 sessions) while the others who received no prophylactic Ca had an AE on 45 occasions (p=0.0141, RR 1.116, CI 1.08-1.15). Data from the registry shows that centers have various approaches to apheresis. One can learn from each other's experience to reduce side effects and improve efficacy. From these data we noted that prophylactic Ca infusion reduced side effects.

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review.

PubMed

Teles, Kaian Amorim; Medeiros-Souza, Patricia; Lima, Francisco Aires Correa; Araújo, Bruno Gedeon de; Lima, Rodrigo Aires Correa

Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

PubMed

Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

2014-12-01

How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Nitrous oxide for the management of labor pain: a systematic review.

PubMed

Likis, Frances E; Andrews, Jeffrey C; Collins, Michelle R; Lewis, Rashonda M; Seroogy, Jeffrey J; Starr, Sarah A; Walden, Rachel R; McPheeters, Melissa L

2014-01-01

We systematically reviewed evidence addressing the effectiveness of nitrous oxide for the management of labor pain, the influence of nitrous oxide on women's satisfaction with their birth experience and labor pain management, and adverse effects associated with nitrous oxide for labor pain management. We searched the MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for articles published in English. The study population included pregnant women in labor intending a vaginal birth, birth attendees or health care providers who may be exposed to nitrous oxide during labor, and the fetus/neonate. We identified a total of 58 publications, representing 59 distinct study populations: 2 studies were of good quality, 11 fair, and 46 poor. Inhalation of nitrous oxide provided less effective pain relief than epidural analgesia, but the quality of studies was predominately poor. The heterogeneous outcomes used to assess women's satisfaction with their birth experience and labor pain management made synthesis of studies difficult. Most maternal adverse effects reported in the literature were unpleasant side effects that affect tolerability, such as nausea, vomiting, dizziness, and drowsiness. Apgar scores in newborns whose mothers used nitrous oxide were not significantly different from those of newborns whose mothers used other labor pain management methods or no analgesia. Evidence about occupational harms and exposure was limited. The literature addressing nitrous oxide for the management of labor pain includes few studies of good or fair quality. Further research is needed across all of the areas examined: effectiveness, satisfaction, and adverse effects.

An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia.

PubMed

Arca, Ercan; Açikgöz, Gürol; Taştan, Halis Bülent; Köse, Osman; Kurumlu, Zafer

2004-01-01

Androgenetic alopecia (AGA) is undoubtedly the most common form of hair loss in males. It is a condition which may cause cosmetic and psychosocial problems in androgen-dependent cases. In this open, randomized and comparative study we evaluated the efficacy of oral finasteride and 5% topical minoxidil treatment for 12 months in 65 male patients with mild to severe AGA. We randomly assigned 40 (61.53%) patients to receive 1 mg/day oral finasteride for 12 months, and 25 (38.47%) patients applied 5% topical minoxidil solution twice daily for 12 months. There were no significant differences between the 2 groups considering age, age of onset of hair loss, family history and type of hair loss (p > 0.05). In the clinical evaluation at the endpoint of treatment, the clinical cure rates (i.e. increased intensity of hair) were 80% (32/40) for the oral finasteride group and 52% (13/25) for the 5% topical minoxidil group. Encountered side effects were all mild, and there was no need to stop the treatment. In the group given oral finasteride, side effects were noted in 7 patients: 6 patients suffered from loss of libido, and 1 patient had an increase in other body hairs; irritation of the scalp was seen in 1 patient in the group administered 5% minoxidil. These adverse events disappeared as soon as the treatment was stopped. The laboratory data on both drug groups did not show any statistically or clinically significant intragroup changes from baseline values to the endpoint (p > 0.05), except the level of serum total testosterone which was increased, and free testosterone and serum prostate-specific antigen in the finasteride group which were statistically decreased from baseline values to the endpoint (p < 0.05). In this comparative study of systemic finasteride and topical minoxidil, it was concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although oral finasteride treatment was more effective (p < 0.05). Adverse events were not considered important either, and these side effects disappeared as soon as the treatment was stopped.

Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

PubMed

Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

2009-11-01

To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

[Blood donor hemovigilance: impact for donor and recipient safety].

PubMed

Hauser, L; Beyloune, A; Simonet, M; Bierling, P

2013-05-01

Since its creation in 1993, hemovigilance has an important place for blood safety. The part concerning donors, as the name suggests, targeted on improvement of donor's safety covers in fact the two points of the transfusion chain with serious adverse events in donor, epidemiologic survey for recipients and post-donation information on the two sides. Organized management and close collaboration between the actors of the transfusion chain are necessary to ensure the effectiveness of the system. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Brazilian keratin hair treatment: a review.

PubMed

Weathersby, Courtney; McMichael, Amy

2013-06-01

Brazilian keratin treatments are widely available products that are used by women all over the world to straighten hair. Marketers of these products claim that the keratin treatments render naturally curly hair more manageable and frizz-free while enhancing color and shine, giving the hair a healthier appearance. Although widely used, there have been virtually no reports of adverse side effects. Unfortunately, many of the products that are applied by salon professionals contain formaldehyde or its derivatives and are being marketed as safe. © 2013 Wiley Periodicals, Inc.

"Diazepam loading": ¿Can a strategy for preventing alcohol withdrawal be used to treat benzodiazepine use disorder?

PubMed

Oliveras, Clara; Fortea, Adriana; Espinosa, Laura; Barrio, Pablo; Lligoña, Anna; Balcells-Olivero, Mercè

2018-04-15

Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are widely used to treat insomnia and anxiety, despite having long-term adverse side effects. (Fortea González, Oriolo, Balcells Oliveró, Sánchez Del Valle & Castellvi, 2017). As with alcohol, continued use can lead to tolerance and dependence phenomena. Discontinuation in such cases can produce abstinence symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y Murnion, 2015).

Dermatotoxicologic clinical solutions: hair dying in hair dye allergic patients?

PubMed

Edwards, Ashley; Coman, Garrett; Blickenstaff, Nicholas; Maibach, Howard

2015-03-01

This article describes how to identify allergic contact dermatitis resulting from hair dye, and outlines interventions and prevention principles for those who wish to continue dyeing their hair despite being allergic. Hair dye chemicals thought to be the most frequent sensitizers are discussed with instructions for health care providers on how to counsel patients about techniques to minimize exposure to allergenic substances. This framework should allow many patients to continue dyeing their hair without experiencing adverse side effects.

Evaluation of nonmemory cognitive parameters in psychiatric patients' pre- and post-electroconvulsive therapy: An observational study.

PubMed

Prakash, Jyoti; Srivastava, Kalpana; Manandhar, Pradeep; Saha, Amitabh

2015-01-01

Possibility of cognitive side effects has made electroconvulsive therapy (ECT) questionable. Variable deficits have been debated in memory cognition. Pattern of changes in nonmemory cognition pre- and post-ECT is not clear. Forty patients undergoing ECT were studied on nonmemory cognitive parameters before ECT, after a course of ECT, and after 4 weeks of last. ECT. Nonmemory cognition improved during the course of ECT and over 4 weeks of ECT. ECT does not affect the nonmemory cognition adversely.

Heat pipes for use in a magnetic field

DOEpatents

Werner, Richard W.; Hoffman, Myron A.

1983-01-01

A heat pipe configuration for use in a magnetic field environment of a fusion reactor. Heat pipes for operation in a magnetic field when liquid metal working fluids are used are optimized by flattening of the heat pipes having an unobstructed annulus which significantly reduces the adverse side region effect of the prior known cylindrically configured heat pipes. The flattened heat pipes operating in a magnetic field can remove 2--3 times the heat as a cylindrical heat pipe of the same cross sectional area.

Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects.

PubMed

Wehling, Martin

2014-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, and this widespread use is complicated by safety issues. A Literature review was conducted. NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. Most adverse effects are related to generalized inhibition of the major targets of NSAIDs: cyclooxygenases I and II. These enzymes are not only involved in pain and inflammation pathogenesis but are also required in the gastrointestinal (GI) tract for mucosal protection and gut motility, and in the kidneys for functional integrity. Thus, the mechanisms of NSAID toxicity are well understood, but the consequences are largely uncontrolled in clinical practice. GI ulcers, including bleeding ulcers, may occur in several percent of all chronic unprotected, high-dose NSAID users. Renal side effects may precipitate renal failure, resulting in acute dialysis and chronic retention. This includes sodium retention, resulting in arterial hypertension, heart failure, and atherosclerotic events. Cardiovascular risk may be tripled by chronic high-dose NSAID use in long-term clinical trials though "real-life studies" indicate lower risk ratios. Off-target side effects include allergic reactions, drug-induced liver injury, and central nervous system effects. Management of pain and inflammation must consider those risks and find alternative drugs or approaches to limit the negative impact of NSAIDs on mortality and morbidity. Alternative drugs, low-dose/short-term use, but especially non-pharmacologic approaches, such as physiotherapy, exercise, neurophysiologic measures, and local therapies, need to be further utilized. The appalling equation "less pain-more deaths/morbidity" ultimately necessitates treatment optimization in the individual patient.

Comparing the effects of cryotherapy with nitrous oxide gas versus topical corticosteroids in the treatment of oral lichen planus.

PubMed

Amanat, Dariush; Ebrahimi, Hooman; Zahedani, Maryam Zahed; Zeini, Nasim; Pourshahidi, Sara; Ranjbar, Zahra

2014-01-01

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa with treatment challenges for clinicians. The objective of this study is to compare the effects of cryotherapy as a new modality with topical corticosteroids as a conventional therapy in the treatment of OLP. Thirty patients with bilateral OLP lesions were selected. From each patient a lesion on one side was chosen randomly for a single session of cryotherapy with nitrous oxide gas and the lesion on the other side received triamcinolone acetonide 0.1% ointment in orabase. Treatment outcome was measured by means of an appearance score, pain score (visual analogue scale), and severity of lesions before treatment and after 2, 4 and 6 weeks of treatment. Paired samples t-test and Wilcoxon test. In both methods of treatment sign score, pain score and severity of lesions was significantly reduced in all follow-up sessions (P<0.05). But the treatment outcome and relapse was not significantly different between the two treatment methods (P>0.05). Cryotherapy with nitrous oxide gas is as effective as topical triamcinolone acetonide in the treatment of OLP with no systemic side effects and needs less patient compliance. It can be considered as an alternative or adjuvant therapy in OLP patients to reduce the use of treatments with adverse effects.

Preferences for 'New' Treatments Diminish in the Face of Ambiguity.

PubMed

Harrison, Mark; Marra, Carlo A; Bansback, Nick

2017-06-01

New products usually offer advantages over existing products, but in health care, most new drugs are 'me-too', comparable in effectiveness and side effects to existing drugs, but with a more ambiguous evidence base around adverse effects. Despite this, new treatments drive increased health care spending, suggesting a preference for 'newness' in this setting. We explore (1) whether preferences for treatments labeled 'new' exist and (2) persist once the ambiguity in the evidence base reflecting newness is described. We use a Canadian general population sample (n = 2837) characterized by their innovativeness in adopting new products in normal markets. We found that innovators/early adopters (n = 173) had significant preferences for 'newer' treatments (B = 0.162, p = 0.038) irrespective of comparable benefits and side effects and all respondents had significant preferences for less ambiguity in benefit/side effect estimates. Notably, when 'newness' was combined with ambiguity, no significant preferences for new treatments were observed regardless of respondent innovativeness. We conclude that preferences for new products exist for some people in health care markets but disappear when the implication of ambiguity in the evidence base for new treatments is communicated. Physicians should avoid describing treatments as 'new' or be mindful to qualify the implications of 'new' treatments in terms of evidence ambiguity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Localized intestinal perforations as a potential complication of brain hypothermic therapy for perinatal asphyxia.

PubMed

Nishizaki, Naoto; Maiguma, Atsuko; Obinata, Kaoru; Okazaki, Tadaharu; Shimizu, Toshiaki

2016-01-01

Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT.

Therapeutic potential of functional selectivity in the treatment of heart failure.

PubMed

Christensen, Gitte Lund; Aplin, Mark; Hansen, Jakob Lerche

2010-10-01

Adrenergic and angiotensin receptors are prominent targets in pharmacological alleviation of cardiac remodeling and heart failure, but their use is associated with cardiodepressant side effects. Recent advances in our understanding of seven transmembrane receptor signaling show that it is possible to design ligands with "functional selectivity," acting as agonists on certain signaling pathways while antagonizing others. This represents a major pharmaceutical opportunity to separate desired from adverse effects governed by the same receptor. Accordingly, functionally selective ligands are currently pursued as next-generation drugs for superior treatment of heart failure. Copyright © 2010 Elsevier Inc. All rights reserved.

A Phase 2 Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2014-10-01

number/communicate to site coordinator N/A Task V.5 (mo 6-47): implement methods to educate/monitor participants on aspects of vit D3 and calcium...potential side effects of vit D3 supplementation CRFs for adverse event reporting have been developed and included in the protocols submitted for IRB...Task VI.3 (mo 6-47): document acceptance of storage sample in the CGRP database and vit D3 study database The process for storage of sample in the

New antibiotics for healthcare-associated pneumonia.

PubMed

Neuner, Elizabeth A; Ritchie, David J; Micek, Scott T

2009-02-01

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

PubMed

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study. Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain. © 2017 by the Society for Academic Emergency Medicine.

Chloral hydrate sedation for magnetic resonance imaging in newborn infants.

PubMed

Finnemore, Anna; Toulmin, Hilary; Merchant, Naz; Arichi, Tom; Tusor, Nora; Cox, David; Ederies, Ash; Nongena, Phumza; Ko, Christopher; Dias, Ryan; Edwards, Anthony D; Groves, Alan M

2014-02-01

The aim of this study was to look for clinically significant adverse effects of chloral hydrate used in a large cohort of infants sedated for magnetic resonance imaging. Case notes of infants who underwent magnetic resonance imaging (MRI) scanning from 2008 to 2010 were reviewed, with patient demographics, sedation dose, comorbidities, time to discharge, and side effects of sedation noted. Four hundred and eleven infants (median [range] postmenstrual age per weight at scan 42 [31(+4) -60] weeks per 3500 g [1060-9900 g]) were sedated with chloral hydrate (median [range] dose 50 [20-80] mg·kg(-1)). In three cases (0.7%), desaturations occurred which prompted termination of the scan. One infant (0.2%) was admitted for additional observation following sedation but had no prolonged effects. In 17 (3.1%) cases, infants had desaturations which were self-limiting or responded to additional inspired oxygen such that scanning was allowed to continue. When adhering to strict protocols, MRI scanning in newborn infants in this cohort was performed using chloral hydrate sedation with a relatively low risk of significant adverse effects. © 2013 John Wiley & Sons Ltd.

Efficacy of Complementary Therapies in the Quality of Life of Breast Cancer Survivors

PubMed Central

Zaidi, Sahar; Hussain, Showket; Verma, Shalini; Veqar, Zubia; Khan, Asiya; Nazir, Sheeraz Un; Singh, Neha; Moiz, Jamal Ali; Tanwar, Pranay; Srivastava, Anurag; Rath, G. K.; Mehrotra, Ravi

2018-01-01

Breast cancer (BC) is the most common cancer diagnosed in women and the second most common cancer overall, ranking as the fifth cause of death from cancer. The chronicity of the disease produces long-term physiological and psychological manifestations, which adversely affect the quality of life of the individual. The primary treatment while managing cancer presents with various debilitating side effects. With the recent advances in treatment techniques that have improved the survival rate, patients suffer from continuing posttreatment complications. Patients seem to cope well with the stress of treatment of BC and sustain a normal life; however, the deterioration in physical well-being makes the patient functionally inefficient. Exercise has been proven to be an effective, safe, and feasible tool in combating the adverse effects of treatment, prevents complications and decreases the risk of BC-specific mortality. This review briefly presents an overview of the burden of the disease and its management strategies. Owing to the heterogeneity of the population and the multitude of therapies they receive, the response of each patient to treatment is different and so is the magnitude of adverse effects. The review discusses the late sequelae following treatment and evidence supporting the role of physical activity in their management. In conclusion, there is a need for personalized physical activity plans to be developed to suit the individual and their circumstances. PMID:29376027

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PubMed

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

PubMed Central

Seyedan, Atefehalsadat; Alshawsh, Mohammed Abdullah; Alshagga, Mustafa Ahmed; Koosha, Sanaz

2015-01-01

Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity. PMID:26640503

The Safety of Intravenous Cyclophosphamide in the Treatment of Rheumatic Diseases.

PubMed

Woytala, Patryk J; Morgiel, Ewa; Łuczak, Anna; Czesak-Woytala, Katarzyna; Wiland, Piotr

2016-01-01

The therapeutic effects of cyclophosphamide (CP) in the treatment of systemic rheumatic diseases are related to its immune suppressive activity. However effective, the application of CP is restricted due to multiple adverse effects. This retrospective study was conducted to determine the frequency of adverse effects attributed to CP toxicity. The study involved 65 patients (17 male; 48 female) receiving intravenous CP between October 2007 and December 2010. The mean age at onset was 51.2 years (range 19-77 years). The most common diagnoses were systemic sclerosis (20), systemic lupus erythematosus (13) and vasculitis (13). The indications for treatment with CP were interstitial lung disease in the course of systemic diseases (33), vasculitis (24), glomerulonephritis (5) and changes in the central nervous system (3). The patients were administered 400-1000 mg CP in intravenous infusions at 2-16 week intervals, with the addition of sodium 2-sulfanylethanesulfonate (mesna) before and after each pulse. Out of 65 patients 40 (60%) reported adverse effects: infections in 24 (37%), nausea in 19 (29%), vomiting in 11 (17%), abdominal pain in 7 (11%) and pancytopenia in one, leading to cessation of the therapy. No association was found between the frequency of side effects and the treatment duration (p = 0.632), age (p = 0.852), diagnosis (p = 0.171) or nominal dose (p = 0.321). As knowledge about CP continues to increase, this medication remains a safe way to treat many rheumatic diseases.

Efficacy of ketamine in improving pain after tonsillectomy in children: meta-analysis.

PubMed

Cho, Hye Kyung; Kim, Kyu Won; Jeong, Yeon Min; Lee, Ho Seok; Lee, Yeon Ji; Hwang, Se Hwan

2014-01-01

The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis. The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.

Six Months of Diazoxide Treatment at Bedtime in Newly Diagnosed Subjects With Type 1 Diabetes Does Not Influence Parameters of β-Cell Function and Autoimmunity but Improves Glycemic Control

PubMed Central

Radtke, Maria Anita; Nermoen, Ingrid; Kollind, Magnus; Skeie, Svein; Sørheim, Jan Inge; Svartberg, Johan; Hals, Ingrid; Moen, Torolf; Dørflinger, Gry Høst; Grill, Valdemar

2010-01-01

OBJECTIVE Continuous β-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control, and autoimmunity markers in the absence of side effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients were randomized to 6 months of treatment with placebo or 100 mg diazoxide at bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3+ regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention. RESULTS Of six dropouts, three were due to perceived side effects; one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3, and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean −0.30 and −0.18 nmol/l in the diazoxide arm and −0.08 and −0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms and remained stable during intervention but was significantly lower compared with nondiabetic subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects and did not measurably affect insulin production but was associated with improved metabolic control. PMID:20028939

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis.

PubMed

Lee, Eun Nam; Lee, Jae Hoon

2016-01-01

Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37-3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85-39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05-1.01, P = 0.05). The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

PubMed Central

2016-01-01

Objectives Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. Methods The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. Results A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37–3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85–39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05–1.01, P = 0.05). Conclusions The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids. PMID:27788221

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

Recent advances in the development of 14-alkoxy substituted morphinans as potent and safer opioid analgesics.

PubMed

Spetea, M; Schmidhammer, H

2012-01-01

Morphine and other opioid morphinans produce analgesia primarily through μ opioid receptors (MORs), which mediate beneficial but also non-beneficial actions. There is a continued search for efficacious opioid analgesics with reduced complications. The cornerstone in the development of 14-alkoxymorphinans as novel analgesic drugs was the synthesis of the highly potent MOR agonist 14-O-methyloxymorphone. This opioid showed high antinociceptive potency but also the adverse effects associated with morphine type compounds. Further developments represent the introduction of a methyl and benzyl group at position 5 of 14-O-methyloxymorphone leading to the strong opioid analgesics 14-methoxymetopon and its 5-benzyl analogue, which exhibited less pronounced side effects than morphine although interacting selectively with MORs. Introduction of arylalkyl substituents such as phenylpropoxy in position 14 led to a series of extremely potent antinociceptive agents with enhanced affinities at all three opioid receptor types. During the past years, medicinal chemistry and opioid research focused increasingly on exploring the therapeutic potential of peripheral opioid receptors by peripheralization of opioids in order to minimize the occurrence of centrally-mediated side effects. Strategies to reduce penetration to the central nervous system (CNS) include chemical modifications that increase hydrophilicity. Zwitterionic 6-amino acid conjugates of 14-Oalkyloxymorphones were developed in an effort to obtain opioid agonists that have limited access to the CNS. These compounds show high antinociceptive potency by interacting with peripheral MORs. Opioid drugs with peripheral site of action represent an important target for the treatment of severe and chronic pain without the adverse actions of centrally acting opioids.

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.

PubMed

Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V; Glick, Stanley D; Ron, Dorit

2010-10-01

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.

Topical Mitomycin C in functional endoscopic sinus surgery.

PubMed

Venkatraman, Vaidyanathan; Balasubramanian, Deepak; Gopalakrishnan, Suria; Saxena, Sunil Kumar; Shanmugasundaram, Nirmal

2012-07-01

In recent literature, there has been an interest in the use of Mitomycin C to reduce post-operative complications following endoscopic sinus surgery. We report our results on a prospective, randomized controlled trial involving 50 patients with chronic bilateral rhino sinusitis. We eliminated various confounding factors by studying a single group of patients, with symmetrical disease, without pre-existing gross anatomical abnormalities. Patients requiring revision sinus surgery were excluded. On completion of the surgery, a cotton pledget soaked in Mitomycin C was placed in one nostril (test) and saline-soaked pledget (control) was placed in the other side of the nose, both in the middle meatus. The side of the nasal cavity receiving the topical Mitomycin C was randomized. The patients were assessed periodically (first week, first month, third month and sixth month) for synechiae formation and presence or absence of their symptoms. At the first week follow up, there was a statistically significant difference in the incidence of synechiae between the saline and Mitomycin C side. Furthermore, there was a statistically significant improvement with regards to patient symptoms (nasal block and discharge) in the Mitomycin C side when compared to the saline side. At the third and sixth month, there was no difference between the two groups. The incidence of adverse tissue reaction (granulation, discharge, polypoidal mucosa and crusting) was less in the Mitomycin C side when compared to the saline side at the first month follow up. Topically applied Mitomycin C reduces the incidence of synechiae in the immediate post-operative period in patients undergoing endoscopic sinus surgery. There is also an improvement in nasal obstruction and discharge with a reduction in the incidence of adverse tissue reaction in the early post-operative period.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

Nicotine Withdrawal, Relapse of Mental Illness, or Medication Side-Effect? Implementing a Monitoring Tool for People With Mental Illness Into Quitline Counseling.

PubMed

Segan, Catherine J; Baker, Amanda L; Turner, Alyna; Williams, Jill M

2017-01-01

Smokers with mental illness and their health care providers are often concerned that smoking cessation will worsen mental health. Smokers with mental illness tend to be more nicotine-dependent and experience more severe symptoms of nicotine withdrawal, some of which are difficult to distinguish from psychiatric symptoms. In addition, smoking cessation can increase the blood levels and hence side effects of some psychotropic medications. Improved monitoring of nicotine withdrawal and medication side effects may help distinguish temporary withdrawal symptoms from psychiatric symptoms and facilitate targeted treatment to help smokers with mental illness manage the acute phase of nicotine withdrawal. The aim of this research was to examine the acceptability and feasibility to quitline counselors of implementing structured assessments of nicotine withdrawal and common medication side effects in people with mental illness who are quitting smoking using a telephone smoking cessation service. Monitoring involves administering (once pre-cessation and at each contact post-cessation) (1) the Minnesota Nicotine Withdrawal Scale, assessing eight symptoms: anger, anxiety, depression, cravings, difficulty concentrating, increased appetite, insomnia, and restlessness and (2) an adverse side effects checklist of 5 to 10 symptoms, for example, dry mouth and increased thirst. Following a 1-day update training in mental health, quitline counselors were asked to offer these assessments to callers disclosing mental illness in addition to usual counseling. Group interviews with counselors were conducted 2 months later to examine implementation barriers and benefits. Barriers included awkwardness in integrating a new structured practice into counseling, difficulty in limiting some callers to only the content of new items, and initial anxieties about how to respond to changes in some symptoms. Benefits included the ability to provide objective feedback on changes in symptoms, as this identified early benefits of quitting, provided reassurance for clients, and provided an opportunity for early intervention where symptoms worsened. Structured monitoring of withdrawal symptoms and medication side effects was able to be integrated into the quitline's counseling and was valued by counselors and clients. Given evidence of its benefits in this limited pilot study, we recommend it be considered for larger-scale adoption by quitlines.

Lesson of the month 2: An unusual adverse reaction associated with pramipexole.

PubMed

Tashkent, Yasmina; Aiyappan, Vinod

2018-06-01

Dopamine agonists such as pramipexole are commonly used in the treatment of restless legs syndrome (RLS) as well as Parkinson's disease. Pramipexole's common side effects are well documented; however, adverse skin reactions are less well known. In this case, a 45-year-old male farmer presented with excessive daytime tiredness and reported a history suggestive of RLS. He was initiated on pramipexole but developed a maculopapular erythematous rash in sun-exposed areas 8 days after its commencement. The skin rash resolved following pramipexole's cessation and it is thought the patient experienced a drug-induced photosensitivity reaction to pramipexole. This case highlights the potential for photosensitivity reactions to pramipexole, which is especially significant in countries like Australia where UV solar radiation is especially high. © Royal College of Physicians 2018. All rights reserved.

Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro.

PubMed

Johnson, Laura P; Walton, Gemma E; Psichas, Arianna; Frost, Gary S; Gibson, Glenn R; Barraclough, Timothy G

2015-06-04

Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation--another method used to modulate gut composition and function--could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

[Local effects of transdermal treatment with rotigotine].

PubMed

Bermejo, Pedro Emilio; Zea, María Ascensión; Alba-Alcántara, Lucía; Ruiz-Huete, Cristina

2013-04-01

Rotigotine is the first transdermal non-ergolinic dopaminergic agonist used in the treatment of Parkinson's disease. It has several important advantages such as once-daily administration, absence of interactions with food, steady levels in plasma and continuous dopaminergic stimulation. Although its systemic side effects are similar to those seen in other dopaminergic agonists, rotigotine also has local side effects derived from the site of application. The aim of this paper is to review those local problems. A retrospective analysis was carried out in order to identify the first 165 patients treated with rotigotine. Patients with intracranial lesions, psychiatric pathology or dementia were excluded. Patients were evaluated before and at two, four and six months after beginning treatment with rotigotine. In all, 94 males and 71 females were identified, with an average age of 65.2 and an average rotigotine daily dose of 11.3 mg. Local side effects were present in 21 patients and they were usually mild. Two patients abandoned the treatment because of these local adverse events, presenting erythema and prurigo. Thirty patients complained about lack of adherence of the patch, specially when it was hot, and 36 about the formation of wrinkles in the patch. None of these problems was associated to motor fluctuations or other complications. Local complications of transdermal rotigotine are mild but frequent. We consider it is necessarily to take them into account to get a better treatment of patients suffering from Parkinson's disease.

Immune checkpoint inhibitor colitis: the flip side of the wonder drugs.

PubMed

Assarzadegan, Naziheh; Montgomery, Elizabeth; Anders, Robert A

2018-01-01

Immune checkpoint inhibitors block the co-inhibitory receptors on T cells to activate their cytotoxic immune function and are rapidly being explored for the treatment of various advanced-stage malignancies. These novel drugs have already significantly increased survival rates. The first available immune checkpoint inhibitors were cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors (such as ipilimumab), followed by programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors (such as pembrolizumab and nivolumab). Anti-PD-1 and anti-PD-L1 therapies have demonstrated better efficacy and tolerability and less severe adverse effects compared to anti-CTLA-4 agents. Idelalisib, a PI3Kδ isoform inhibitor, is another immunotherapeutic agent that is often classified separately and is currently used in treatment of chronic lymphocytic leukemia and non-Hodgkin lymphomas. Despite successful therapeutic responses, immune-related adverse events have been reported with the use of these agents. The gastrointestinal side effects, particularly diarrhea, are among the most commonly reported symptoms. The histologic features of immune checkpoint inhibitor-associated colitis show a spectrum of patterns of injury among various drug classes. There is significant overlap between immune checkpoint inhibitor-associated colitis and other colitides, making the differential diagnosis difficult-especially in the absence of clinical history. The histopathology data on immune checkpoint inhibitor-associated colitis are limited. Here we review clinical features as well as various histologic patterns of colitis associated with these groups of medications.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

PubMed

Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

2016-10-01

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peripheral μ-opioid receptor mediated inhibition of calcium signaling and action potential-evoked calcium fluorescent transients in primary afferent CGRP nociceptive terminals.

PubMed

Baillie, Landon D; Schmidhammer, Helmut; Mulligan, Sean J

2015-06-01

While μ-opioid receptor (MOR) agonists remain the most powerful analgesics for the treatment of severe pain, serious adverse side effects that are secondary to their central nervous system actions pose substantial barriers to therapeutic use. Preclinical and clinical evidence suggest that peripheral MORs play an important role in opioid analgesia, particularly under inflammatory conditions. However, the mechanisms of peripheral MOR signaling in primary afferent pain fibres remain to be established. We have recently introduced a novel ex vivo optical imaging approach that, for the first time, allows the study of physiological functioning within individual peripheral nociceptive fibre free nerve endings in mice. In the present study, we found that MOR activation in selectively identified, primary afferent CGRP nociceptive terminals caused inhibition of N-type Ca(2+) channel signaling and suppression of action potential-evoked Ca(2+) fluorescent transients mediated by 'big conductance' Ca(2+)-activated K(+) channels (BKCa). In the live animal, we showed that the peripherally acting MOR agonist HS-731 produced analgesia and that BKCa channels were the major effectors of the peripheral MOR signaling. We have identified two key molecular transducers of MOR activation that mediate significant inhibition of nociceptive signaling in primary afferent terminals. Understanding the mechanisms of peripheral MOR signaling may promote the development of pathway selective μ-opioid drugs that offer improved therapeutic profiles for achieving potent analgesia while avoiding serious adverse central side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Pain management in home hospice care].

PubMed

Sakai, T; Sato, A

1998-12-01

Among 35 cases with terminal home care cancer patients, 23 (65.7%) cases developed pain. Twenty of these cases (87%) were treated with morphine. MS-contin and Anpec (suppositorium) were given to the patients. The two forms were jointly administered in 20% of them. NSAIDS and other adjuvant analgesics were given to 85% of them. Average dose of morphine were 173.5 +/- 357.5 mg. Adverse morphine side effects were treated with medication. In any case morphine administration was not discontinued due to its adverse effects. Some 82% of the patients died at home. No case dropped out of home care due to unsuccessful pain management. Successful pain management is necessary to implement home terminal care, and both patient and family should fully understand the status and prognosis of the incurable disease. Moreover, medical professionals (home care doctors, home care nurses and hospital doctors) should collaborate to form the temporal, adequate and seamless networking in caring and supporting terminal patients and their families.

Comparative analysis of Lacistema pubescens and dexamethasone on topical treatment of skin inflammation in a chronic disease model and side effects.

PubMed

da Silva, Josiane M; Conegundes, Jéssica L M; Pinto, Nícolas C C; Mendes, Renata F; Castañon, Maria Christina M N; Scio, Elita

2018-04-01

This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases. © 2018 Royal Pharmaceutical Society.

Reverse saphenous conduit flap in small animals: Clinical applications and outcomes.

PubMed

Elliott, Ross C

2014-08-20

Due to the lack of skin elasticity defects of the distal hind limb can be a challenge to close. This article assesses a well-described, but completely under-used technique for closure of wounds on the distal tarsus. The technique was used with good success in six cases presenting to the Bryanston Veterinary Hospital with a wide range of underlying pathology ranging from trauma to neoplastic disease of the tarsus. All six cases were treated with a reverse saphenous conduit flap and two of them underwent radiation therapy with no adverse side effects. All cases showed excellent results with a very low degree of flap necrosis that never exceeded 15% of the total flap area. This skin flap provides an excellent treatment method that is reliable in closure of defects of the distal tarsus with few adverse effects. To the author's knowledge there has been only one previously published report on the clinical use of this type of skin flap, even though the flap is well described in most texts.

Kinetic studies of L-asparaginase from Penicillium digitatum.

PubMed

Shrivastava, Abhinav; Khan, Abdul Arif; Shrivastav, Archana; Jain, Sudhir K; Singhal, Pradeep K

2012-01-01

L-Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and other related malignancies. Its further use includes reduction of asparagine concentration in food products, which may lead to formation of acrylamide. Currently bacterial asparaginase is produced at industrial scale, but the enzyme isolated from bacterial origin is often associated with adverse reactions. These side effects require development of asparaginase from alternative sources. In the present study, Penicillium digitatum was explored for the production of extracellular L-asparaginase using modified Czapek-Dox media. The enzyme was purified about 60.95-fold and then kinetic study showed that the Km value of the enzyme was 1 × 10⁻⁵ M. The optimum pH and temperature for the enzyme were 7.0 and 30°C, respectively. The optimum incubation period for L-asparaginase was 15 min. This work concludes that this enzyme can be a suitable candidate due to its strong kinetic properties, and further research can usher into development of asparaginase formulation from fungal origin with less adverse effects.

Considerations of sex and gender differences in preclinical and clinical trials.

PubMed

Raz, Limor; Miller, Virginia M

2012-01-01

Women continue to be underrepresented in clinical trials, particularly in Phases I and II of experimental drug studies in spite of legislative guidelines in the USA, Canada, the European Union, Australia, and Japan requiring the inclusion of women in clinical trials. As such, women remain a vulnerable population subject to the adverse effects of pharmacological therapies. Thus, women experience higher rates of adverse drug reactions than do men and for women of reproductive age or who may be pregnant, therapeutic options may be limited. This chapter provides a brief history of inclusion of sex and gender as variables in clinical trials, summarizes governmental legislation for consideration of sex and gender in clinical trials and provides specific examples of drugs which have been withdrawn from the market because of side effects in women. Additional information related to sex and gender in preclinical testing, trial design, challenges to recruitment of women for clinical trials and statistical methods for analysis of data also is considered.

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

Rediscovering Chirality - Role of S-Metoprolol in Cardiovascular Disease Management.

PubMed

Mohan, Jagdish C; Shah, Siddharth N; Chinchansurkar, Sunny; Dey, Arindam; Jain, Rishi

2017-06-01

The process of drug discovery and development today encompass a myriad of paths for bringing a new therapeutic molecule that has minimal adverse effects and of optimal use to the patient. Chirality was proposed in the direction of providing a purer and safer form of drug [Ex- cetrizine and levocetrizine]. Decades have passed since the introduction of this concept and numerous chiral molecules are in existence in therapeutics, yet somehow this concept has been ignored. This review aims to rediscover the ignored facts about chirality, its benefits and clear some common myths considering the example of S-Metoprolol in the management of Hypertension and other cardiovascular diseases. Relevant articles from Pubmed, Embase, Medline and Google Scholar were searched using the terms "Chiral", "Chirality", "Enantiomers", "Isomers", "Isomerism", "Stereo-chemistry", and "S-Metoprolol". Out of 103 articles found 17 articles mentioning in general about the concept of chirality and articles on study of S-metoprolol in various cardiovascular diseases were then reviewed. Many articles mention about the importance of chirality yet the concept has not been highlighted much. Clear benefits with chiral molecules have been documented for various drug molecules few amongst them being anaesthetics, antihypertensives, antidepressants. Benefits of S-metoprolol over racemate are also clear in terms of responder rates, dose of administration and adverse effects profile in various cardiovascular diseases. Chirality is a good way forward in providing a new drug molecule which is safe with lesser pharmacokinetic and pharmacodynamics variability, lesser side effects and more potent action. S-metoprolol is chirally pure form of racemate metoprolol and has lesser side effects, is safer in patients of COPD and Diabetes who also have hypertension and comparable responder rates at half the doses when compared to racemate.

The pharmacokinetics of colistin in patients with cystic fibrosis.

PubMed

Reed, M D; Stern, R C; O'Riordan, M A; Blumer, J L

2001-06-01

The safety and pharmacokinetics of colistin were determined after first dose (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t1/2), mean residence time (MRT), steady-state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first-dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first-dose and steady-state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty-one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin-induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin-induced nephrotoxicity. No relationship between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.

N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease

PubMed Central

Olivares, David; Deshpande, Varun K.; Shi, Ying; Lahiri, Debomoy K.; Greig, Nigel H.; Rogers, Jack T.; Huang, Xudong

2016-01-01

Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer’s disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson’s disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine—as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine’s therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine’s tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy. PMID:21875407

Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis.

PubMed

Alomar, Soha; King, Nicolas K K; Tam, Joseph; Bari, Ausaf A; Hamani, Clement; Lozano, Andres M

2017-01-01

The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems. This review summarizes the data on the development of speech problems after thalamic surgery. A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014. Of a total of 2,320 patients, 19.8% (confidence interval: 14.8-25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8-22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5-52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1-27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4-13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6-50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients. Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1% hydrocortisone ointment in the treatment of childhood atopic dermatitis: a pilot study.

PubMed

Udompataikul, Montree; Limpa-o-vart, Dipenn

2012-03-01

Atopic dermatitis (AD) is a common chronic relapsing disease particularly affecting children. The emollient used for protection of skin barrier function is the standard treatment for patients with AD. Currently, there is a growing interest in the use of nonsteroidal anti-inflammatory agents such as dexpanthenol (vitamin B5) as an alternative treatment. To compare the effectiveness of 5% dexpanthenol (DT) ointment with 1% hydrocortisone (HC) ointment in childhood AD therapy. Patients were treated topically with 5% DT ointment on the right side of the body and 1% HC ointment on the other side twice daily for 4 weeks. The clinical responses were evaluated by SCORAD (Scoring Atopic Dermatitis index) with statistical analysis using paired t-test. Of the 30 children enrolled, 26 completed the protocol; mean age was 7.19 years. The average baseline SCORAD score of the DT-treated side and the HC-treated side was 30.95 and 30.54, respectively. There was no statistically significant difference in SCORAD score reduction between the 2 agents. The edematous score of the HC-treated side exhibited faster resolution than that of the DT-treated side, with a statistically significant difference at week 1 and without a statistically significant difference at weeks 2 to 4. The lichenification response rate of HC treatment was more rapid than that of DT treatment; however, there was no statistical group difference. No adverse events were observed with either agent. The effectiveness of 5% DT ointment is equal to that of 1% HC ointment. DT ointment may be used as alternative treatment in mild to moderate childhood AD therapy.

Effects of first premolar extraction on maxillary and mandibular third molar angulation after orthodontic therapy

PubMed Central

Gohilot, Avinash; Pradhan, Tejashri; Keluskar, Kanhoba Mahabaleshwar

2012-01-01

Background/Aims To compare the change in the angulation of developing mandibular third molar in both first premolar extraction and non-extraction cases and to determine whether premolar extraction results in a more mesial movement of the mandibular buccal segment and causes favorable rotational changes in the mandibular third molar tilt, which can enhance later eruption of the third molars. Materials and methods Pretreatment (T1) and post treatment (T2) panoramic radiographs were taken of 25 subjects (age 14–19 years) who had been treated by the extraction of all the first premolars and 25 subjects who had been treated with non-extraction. The horizontal reference plane was used to measure and compare the changes in the angles of the developing mandibular third molars. Results The mean uprighting of the maxillary third molars seen in the extraction group was 4 ± 9° on the left side and −17 ± 13° on the right side following treatment (T2 _ T1). For the non-extraction group the mean difference was −16 ± 12° on the left side and 2 ± 13° on the right side. There was a statistically significant difference between the groups (P _ 0.021 on the right side and P _ 0.041 on the left side). Mandibular 3rd molars in extraction group showed no statistical significant change in the angulation. Conclusion Premolar extractions had a positive influence on the developing maxillary third molar angulations both on right and left. Mandibular 3rd molar have shown change in the angulation but not statistically significant. Non-extraction therapy did not have any adverse effect. PMID:25737843

Effects of first premolar extraction on maxillary and mandibular third molar angulation after orthodontic therapy.

PubMed

Gohilot, Avinash; Pradhan, Tejashri; Keluskar, Kanhoba Mahabaleshwar

2012-01-01

To compare the change in the angulation of developing mandibular third molar in both first premolar extraction and non-extraction cases and to determine whether premolar extraction results in a more mesial movement of the mandibular buccal segment and causes favorable rotational changes in the mandibular third molar tilt, which can enhance later eruption of the third molars. Pretreatment (T1) and post treatment (T2) panoramic radiographs were taken of 25 subjects (age 14-19 years) who had been treated by the extraction of all the first premolars and 25 subjects who had been treated with non-extraction. The horizontal reference plane was used to measure and compare the changes in the angles of the developing mandibular third molars. The mean uprighting of the maxillary third molars seen in the extraction group was 4 ± 9° on the left side and -17 ± 13° on the right side following treatment (T2 _ T1). For the non-extraction group the mean difference was -16 ± 12° on the left side and 2 ± 13° on the right side. There was a statistically significant difference between the groups (P _ 0.021 on the right side and P _ 0.041 on the left side). Mandibular 3rd molars in extraction group showed no statistical significant change in the angulation. Premolar extractions had a positive influence on the developing maxillary third molar angulations both on right and left. Mandibular 3rd molar have shown change in the angulation but not statistically significant. Non-extraction therapy did not have any adverse effect.

The non-target impact of spinosyns on beneficial arthropods.

PubMed

Biondi, Antonio; Mommaerts, Veerle; Smagghe, Guy; Viñuela, Elisa; Zappalà, Lucia; Desneux, Nicolas

2012-12-01

Spinosyn-based products, mostly spinosad, have been widely recommended by extension specialists and agribusiness companies; consequently, they have been used to control various pests in many different cropping systems. Following the worldwide adoption of spinosad-based products for integrated and organic farming, an increasing number of ecotoxicological studies have been published in the past 10 years. These studies are primarily related to the risk assessment of spinosad towards beneficial arthropods. This review takes into account recent data with the aim of (i) highlighting potentially adverse effects of spinosyns on beneficial arthropods (and hence on ecosystem services that they provide in agroecosystems), (ii) clarifying the range of methods used to address spinosyn side effects on biocontrol agents and pollinators in order to provide new insights for the development of more accurate bioassays, (iii) identifying pitfalls when analysing laboratory results to assess field risks and (iv) gaining increasing knowledge on side effects when using spinosad for integrated pest management (IPM) programmes and organic farming. For the first time, a thorough review of possible risks of spinosad and novel spinosyns (such as spinetoram) to beneficial arthropods (notably natural enemies and pollinators) is provided. The acute lethal effect and multiple sublethal effects have been identified in almost all arthropod groups studied. This review will help to optimise the future use of spinosad and new spinosyns in IPM programmes and for organic farming, notably by preventing the possible side effects of spinosyns on beneficial arthropods. Copyright © 2012 Society of Chemical Industry.

Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects.

PubMed

Strauss, W E; Parisi, A F

1988-10-01

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

Enalapril and diltiazem co-administration and respiratory side effects of enalapril.

PubMed

Franová, S; Nosál'ová, G; Antosová, M; Nosál', S

2005-01-01

A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatory neuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administration of enalapril and the defense reflexes (cough and bronchoconstriction) of the airways in experimental animals, as well as the possibility of their pharmacological restriction with simultaneous diltiazem administration. Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchial area in non-anesthetized cats. The reactivity of tracheal smooth muscles of the airways to bronchoconstrictor mediators (histamine 10 nM - 1 mM, acetylcholine 10 nM - 1 mM and KCl 1 mM - 100 mM) was evaluated by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days. The results showed that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to histamine and KCl. Simultaneous administration of enalapril together with diltiazem significantly decreased the enalapril induced cough, and decreased enalapril induced hyperreactivity of tracheal smooth muscles to KCl. The results showed a partially protective effect of diltiazem and enalapril co-administration on the respiratory adverse effects induced by enalapril therapy.

Rescue pre-operative treatment with Lugol's solution in uncontrolled Graves' disease.

PubMed

Calissendorff, Jan; Falhammar, Henrik

2017-05-01

Graves' disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol's solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005-2015 and treated with Lugol's solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Twenty-seven patients were included. Lugol's solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5-9 days of iodine therapy (free T4 53-20 pmol/L, P  = 0.0002; free T3 20-6.5 pmol/L, P  = 0.04; heart rate 87-76 beats/min P  = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n  = 2, rash and vomiting n  = 1, swelling of fingers n  = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Treatment of uncontrolled hyperthyroidism with Lugol's solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol's solution could be recommended pre-operatively in Graves' disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred. © 2017 The authors.

Efficacy and side-effects of a semi-individualized Chinese herb mixture "Tiáo Gēng Tāng" for menopausal syndrome in China.

PubMed

Jia, Man; Kluwe, Lan; Liu, Hui-Cong; Tang, Qian-Jue; Liu, Lian; Wang, Zhen-Zhen; Tian, Li-Xia; Zhao, Li; Chen, Ying-Chao; Friedrich, Reinhard E; Sun, Zhuo-Jun; Xu, Lian-Wei

2015-01-01

Chinese herbal medicine is an alternative therapy for menopausal problems and is widely practiced in China and many other Asian countries. However, efficacies and side-effects are rarely assessed according to the standards of evidence-based medicine. This is a prospective observatory study following efficacy and side-effects of a semi-individualized Chinese herbal mixture "Tiáo Gēng Tāng (TGT)" in 30 patients for 3 months. Another group of 30 patients receiving hormone therapy with tibolone was included as a positive comparison. Common questionnaire-based measuring instruments were: modified Kupperman index, menopause rating scale, life quality and Chinese medical symptom scale (CMSS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were determined before and three months after the treatments. Significant improvement was seen in overall scores of all the four measurements in both groups. For some symptoms, including dry mouth, tinnitus, poor appetite and constipation, TGT was more effective than tibolone. For psychosocial and sexual sub-scales of life quality, tibolone has a slightly higher remedy rate than TGT. TGT lowered FSH and LH significantly, as tibolone did, but elevated E2 significantly less than tibolone. Various adverse events, including body weight increase, abdomen discomfort, nausea/vomiting, emotional instability, pressure in breasts and dizziness, were reported by patients treated with tibolone, whereas only diarrhea was observed in two patients treated with TGT. TGT alleviates menopausal symptoms with similar efficacy as tibolone but has fewer side effects. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparison of efficacy and side-effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36-week prospective study.

PubMed

Singh, S; Khandpur, S; Sharma, V K; Ramam, M

2013-11-01

Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator's global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Thirty five patients were recruited- 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36 weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P = 0.06), mean PGA score in PUVA was 4.58 ± 2.23 and in PUVA sol group was 6 ± 2.08 (P = 0.13), mean IGA score was 3.08 ± 1.68 in PUVA and 1.79 ± 0.57 in PUVA sol group (P = 0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P = 0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis.

PubMed

Luo, L; Yuan, X; Huang, W; Ren, F; Zhu, H; Zheng, Y; Tang, L

2015-05-01

Hypercholesterolaemia is a pivotal risk factor for cardiovascular and cerebrovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with ezetimibe. Combination therapy is more effective because of its complementary approach, which has major benefits for patients with unmanageable lipid levels. Extensive application of combination therapy has resulted in an increased incidence of side-effects, which has raised our concern. To evaluate the evidence associated with the safety of coadministration of ezetimibe with statins. Three electronic databases were searched (PubMed, EMBASE and Cochrane Library) from January 2002 to October 2014. Two independent reviewers critically identify randomised controlled trials (RCT), extracted the data and assessed trial quality. A total ot 20 RCT met inclusion criteria, including 14,856 patients. A fixed-effects model was used for meta-analysis to assess the safety of combination therapy. Coadministration of ezetimibe and statins did not result in significant increases in total adverse events (30% vs 29%, P = 0.34), serious adverse events (2% vs 1.6%, P = 0.81), treatment discontinuations (3.5% vs 2.9%, P = 0.22), gastrointestinal adverse events (5% vs 4%, P = 0.08), allergic reactions or rashes (0.9% vs 1.3%, P = 0.33), creatine kinase > 10 × upper limit of normal (ULN) (0.2% vs 0.2%, P = 0.86), alanine aminotransferase > 3 × ULN (0.5% vs 0.4%, P = 0.96) and aspartate aminotransferase > 3 × ULN (0.4% vs 0.4%, P = 0.58). The incidence of adverse events was similar between ezetimibe-statin combination therapy and statin monotherapy; thus, we recommend combination therapy for patients with hypercholesterolaemia at high risk for cardiovascular and cerebrovascular disease. © 2015 Royal Australasian College of Physicians.

Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

PubMed

Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

2011-04-01

Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced. Copyright © 2011. Published by Elsevier Ltd.

Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

PubMed Central

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-01-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients. PMID:24716172

Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis

PubMed Central

Iborra, Marisa; Álvarez-Sotomayor, Diego; Nos, Pilar

2014-01-01

Ulcerative colitis (UC) is a chronic, relapsing, and remitting inflammatory disease involving the large intestine (colon). Treatment seeks to break recurrent inflammation episodes by inducing and maintaining remission. Historically, oral systemic corticosteroids played an important role in inducing remission of this chronic disease; however, their long-term use is limited and can lead to adverse events. Budesonide is a synthetic steroid with potent local anti-inflammatory effects and low systemic bioavailability due to high first-pass hepatic metabolism. Several studies have demonstrated oral budesonide’s usefulness in treating active mild to moderate ileocecal Crohn’s disease and microscopic colitis and in an enema formulation for left sided UC. However, there is limited information regarding oral budesonide’s efficacy in UC. A novel oral budesonide formulation using a multimatrix system (budesonide-MMX) to extend drug release throughout the colon has been developed recently and seems to be an effective treatment in active left sided UC patients. This article summarizes budesonide’s long-term safety and efficacy in treating UC. PMID:24523594

Autophagy therapeutic potential of garlic in human cancer therapy.

PubMed

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-07-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

Managing atrial fibrillation in the elderly: critical appraisal of dronedarone.

PubMed

Trigo, Paula; Fischer, Gregory W

2012-01-01

Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.

Efficacy of functional microarray of microneedles combined with topical tranexamic acid for melasma

PubMed Central

Xu, Yang; Ma, Renyan; Juliandri, Juliandri; Wang, Xiaoyan; Xu, Bai; Wang, Daguang; Lu, Yan; Zhou, Bingrong; Luo, Dan

2017-01-01

Abstract To evaluate the efficacy of a functional microarray of microneedles (MNs) plus topical tranexamic acid (TA) for melasma in middle-aged women in China. Thirty female subjects with melasma were enrolled in this study. The left or right side of the face was chosen randomly to be pretreated with a functional microarray of MNs, followed by topical 0.5% TA solution once per week for 12 weeks. The other half-face was the control, treated with a sham device plus topical 0.5% TA solution. At baseline and at weeks 4, 8, and 12 of treatment, clinical (photographic) evaluations and parameters determined by Visia were recorded. At baseline and week 12, patient satisfaction scores and the biophysical parameters measured by Mexameter were also recorded. Side effects were evaluated at baseline and at the end of the 12 weeks. In total, 28 women (93.3%) completed the study. The brown spots’ scores measured by Visia were significantly lower on the combined therapy side than on the control side at 12 weeks after starting treatment; there was no significant difference between sides at 4 or 8 weeks. After 12 weeks, melanin index (MI) decreased significantly in both 2 groups, and the MI was significantly less on the combined side at week 12. Transepidermal water loss, roughness, skin hydration, skin elasticity, and erythema index showed no significant differences between 2 sides at baseline, 4, 8, and 12 weeks after treatment. Physicians’ evaluations of photographs showed better results at week 12 with combined therapy: >25% improvement was observed in the MNs plus TA side in 25 patients, and in the TA side in only 10 patients. Subjective satisfaction scores on both sides increased significantly. The participants were more satisfied with the results of the combined therapy side than the control side. No obvious adverse reactions were observed throughout the study. Combined therapy with a functional microarray of MNs and topical TA solution is a promising treatment for melasma. PMID:28489798

Mosquito bite anaphylaxis: immunotherapy with whole body extracts.

PubMed

McCormack, D R; Salata, K F; Hershey, J N; Carpenter, G B; Engler, R J

1995-01-01

Adverse reactions to mosquito bites have been recognized for some time. These usually consist of large local swellings and redness, generalized urticaria, angioedema and less easily definable responses such as nausea, dizziness, headaches, and lethargy. We report two patients who experienced systemic anaphylaxis from mosquito bites. Both were skin tested and given immunotherapy using whole body mosquito extracts. Skin testing using whole body mosquito extracts was positive to Aedes aegypti at 1/1,000 weight/volume (wt/vol) in one patient and to Aedes aegypti at 1/100,000 wt/vol, and Culex pipiens at 1/10,000 wt/vol in the other. Skin testing of ten volunteers without a history of adverse reactions to mosquito bites was negative. Immunotherapy using these extracts resulted in resolution of adverse reactions to mosquito bites in one patient and a decrease in reactions in the other. Immunotherapy with whole body mosquito extracts is a viable treatment option that can play a role in patients with mosquito bite-induced anaphylaxis. It may also result in severe side effects and one must determine the benefit versus risks for each individual patient.

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

PubMed

Sunara, Petra; Krnic, Darko; Puljak, Livia

2017-11-01

Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PubMed

Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

2001-06-01

To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

Neuropsychiatric Effects of Antimicrobial Agents.

PubMed

Zareifopoulos, Nicholas; Panayiotakopoulos, George

2017-05-01

Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system. The neuropsychiatric effects of antimicrobial drugs are extensively documented in the literature. A number of antimicrobial drugs have the potential to exert CNS effects and many are associated with stimulant, psychotomimetic and epileptogenic properties, mediated by GABA antagonism (beta-lactams, quinolones and clarithromycin), NMDA agonism (D-cycloserine, aminoglycosides, and perhaps quinolones), MAO inhibition (linezolid, metronidazole and isoniazid weakly) as well as more exotic mechanisms, as in the case of trimethoprim, isoniazid, ethambutol, rifampicin and the tetracyclines. While those effects are generally undesirable, they may also under certain circumstances be beneficial, and further research is warranted in that direction.

Efficacy of Slimming Cream Containing 3.5% Water-Soluble Caffeine and Xanthenes for the Treatment of Cellulite: Clinical Study and Literature Review

PubMed Central

Byun, Sang-Young; Kwon, Soon-Hyo; Heo, Su-Hak; Shim, Jae-Seong; Du, Mi-Hee

2015-01-01

Background Cellulite is a 'cottage cheese-like' cutaneous change caused by subcutaneous fat bulging into the dermis that usually leads to cosmetic problems. Slimming cream containing 3.5% water-soluble caffeine and xanthenes exhibits a lipolytic effect with penetration into the dermis. Objective To evaluate the efficacy and safety of slimming cream for the treatment of cellulite. Methods Fifteen subjects with cellulite applied slimming cream to the thighs and inner side of the upper arms twice daily for 6 weeks. Efficacy was assessed using a standard visual scale, changes in the circumferences of the thighs and upper arms, and patient satisfaction by a questionnaire at baseline, week 3, and week 6. Safety was assessed by inquiring about adverse events through questionnaires. Results The standard visual scale score improved significantly by 0.49 points (19.8%) at week 6. Thigh and upper-arm circumferences decreased by 0.7 cm (1.7%) and 0.8 cm (2.3%), respectively, at week 6. Slight itching and transient flushing were commonly reported, but no serious adverse event occurred. Conclusion The slimming cream tested appears to be effective for the treatment of cellulitis without serious adverse effects. However, additional large clinical trials are required to confirm the efficacy and safety of slimming cream for the treatment of cellulitis. PMID:26082579

Solar Array Hysteresis and its Interaction with the MPPT System

NASA Astrophysics Data System (ADS)

Fernandez, A.; Baur, C.; Gomez-Carpintero, F.

2014-08-01

It is well known that solar cells have a capacitance in parallel which value changes with the voltage. Depending on the section arrangement on the Solar Array, the power conversion unit connected to it will see a smaller or larger capacitance value and will have to cope with its adverse effects. In the case of converters with an MPPT, this capacitance gives place to an hysteresis effect that might shift the tracking point, reducing the power extracted from the Solar Array. This paper explores the different sides of this issue, from capacitance modelling to the effects on the MPPT. Additionally, this paper analyses a similar interaction between MPPTs and commercial SAS.

Effects of antihypertensive agents on sexual function.

PubMed

Weiss, R J

1991-12-01

Patient compliance with antihypertensive therapy can be improved by minimizing drug-induced sexual dysfunction. Impotence, decreased libido, impaired ejaculation and gynecomastia are potential side effects, depending on the agent prescribed. Centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers and potassium-sparing diuretics are the drugs most often associated with sexual dysfunction. Thiazide diuretics cause impotence but may otherwise play a minimal role in sexual dysfunction. Alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel blockers have little adverse effect on sexual function. It is important to obtain an adequate history before and after initiating therapy. If sexual dysfunction develops in a patient, a different class of medication can be tried.

Designing Safer Analgesics via μ-Opioid Receptor Pathways.

PubMed

Chan, H C Stephen; McCarthy, Dillon; Li, Jianing; Palczewski, Krzysztof; Yuan, Shuguang

2017-11-01

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. It is therefore imperative that both academia and industry develop novel μOR analgesics which retain their opioid analgesic properties but with fewer or no adverse effects. In this review we outline recent progress towards the discovery of safer opioid analgesics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Designing Safer Analgesics via μ-Opioid Receptor Pathways

PubMed Central

Chan, H.C. Stephen; McCarthy, Dillon; Li, Jianing; Palczewski, Krzysztof; Yuan, Shuguang

2017-01-01

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. It is therefore imperative that both academia and industry develop novel μOR analgesics which retain their opioid analgesic properties but with fewer or no adverse effects. In this review we outline recent progress towards the discovery of safer opioid analgesics. PMID:28935293

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.

Adherence to malaria prophylaxis among Peace Corps Volunteers in the Africa region, 2013.

PubMed

Landman, Keren Z; Tan, Kathrine R; Arguin, Paul M

2015-01-01

Although malaria can be prevented with prophylaxis, it is diagnosed in over 100 Africa-region Peace Corps Volunteers annually. This suggests that prophylaxis non-adherence is a problem in these non-immune travelers. We investigated Volunteers' knowledge, attitudes, and practices regarding prophylaxis using an internet-based survey during August 19-September 30, 2013. Adherence was defined as taking doxycycline or atovaquone-proguanil daily, or taking mefloquine doses no more than 8 days apart. The survey was sent to 3248 Volunteers. Of 781 whose responses were analyzed, 514 (73%) reported adherence to prophylaxis. The most common reasons for non-adherence were forgetting (n = 530, 90%); fear of long-term adverse effects (LTAEs; n = 316, 54%); and experiencing adverse events that Volunteers attributed to prophylaxis (n = 297, 51%). Two hundred fourteen (27%) Volunteers reported not worrying about malaria. On multivariate analysis controlling for sex and experiencing adverse events Volunteers attributed to prophylaxis, the factor most strongly associated with non-adherence was being prescribed mefloquine (OR 5.4, 95% confidence interval 3.2-9.0). We found moderate adherence and a prevailing fear of LTAEs among Volunteers. Strategies to improve prophylaxis adherence may include medication reminders, increasing education about prophylaxis safety and malaria risk, and promoting prompt management of prophylaxis side effects. Published by Elsevier Ltd.

Comparison of the Efficacy, Side Effects, and Cost of Modafinil and Intranasal Mometasone Furoate in Obstructive Sleep Apnea-Hypopnea Syndrome: A Preliminary Clinical Study

PubMed Central

Zhang, Shujia; Duan, Zhongnin

2018-01-01

Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated episodes of reduction in airflow due to the collapse of the upper airway during sleep. The aim of this study was to compare clinical outcome, side effects, and cost of treatment between modafinil and intranasal mometasone furoate in patients with OSAHS. Material/Methods Patients with OSAHS (N=250) were divided into two groups: the modafinil group (MG) (N=125) were treated with 100 mg modafinil twice a day; the intranasal mometasone furoate group (IMFG) (N=125) were treated with 100 μg of intranasal mometasone furoate in the evening. Quality of life, grading of OSAHS, plain-film radiography, the adenoidal-nasopharyngeal ratio (AN ratio), side effects, cost of treatment, and beneficial effects after discontinuation of treatment were evaluated for all patients. Results Duration of sleep apnea was significantly reduced in the IMFG compared with the MG (p=0.0145, q=9.262). Modafinil and intranasal mometasone furoate both had moderate effects on improvement of the OSAHS score. The IMFG showed a significantly greater beneficial effect on the AN ratio when compared with the MG (p=0.0001, q=6.584). No adverse events of treatment with modafinil and intranasal mometasone furoate were reported. Cost of treatment and beneficial effect after discontinuation were both significantly greater for the IMFG compared with the MG. Conclusions The findings of this preliminary clinical study were that for patients diagnosed with OSAHS, night-time treatment with intranasal mometasone furoate was more effective than modafinil. PMID:29749371