[Thyroid and treatment with amiodarone diagnosis, therapy and clinical management].

PubMed

Mikosch, Peter

2008-01-01

Amiodarone is a frequently used antiarrhythmic drug with a high antiarrhythmic potency. However, beside its antiarrhythmic effects Amiodarone also reveals a variety of adverse effects and drug-related complications. The affected organs include the eyes, skin, lungs, nervous system, liver, gastrointestinal tract and the thyroid. The thyroid is one of the most frequently affected organs by Amiodarone. An altered hormone equilibrium always occurs and has to be distinguished from Amiodarone induced hyperthyroidism and hypothyroidism. The differentiation of these states frequently causes problems and may even be a diagnostic and therapeutic challenge in certain cases. The article gives an overview on the interactions between Amiodarone and the thyroid, the diagnostic and therapeutic options and management strategies of patient on Amiodarone therapy in the view of thyroid function.

Peripheral amiodarone-related phlebitis: an institutional nursing guideline to reduce patient harm.

PubMed

Spiering, Mary

2014-01-01

Intravenous amiodarone is one of the most widely used antiarrythmics for the treatment of atrial fibrillation with rapid ventricular response. Peripheral amiodarone infusion, however, often causes pain during infusion and subsequent phlebitis.Data collection on a cardiac telemetry unit revealed a high rate of phlebitis. A multidisciplinary team developed and implemented amiodarone peripheral infusion guidelines. The pre-guideline phlebitis rate was 85% and post-guideline rate was 38%, representing a 47% change or improvement. An additional finding was that the severity of phlebitis was reduced, as well. The results of this study suggest that the implementation of a peripheral amiodarone infusion guideline reduced the incidence and severity of amiodarone-related phlebitis in the cardiac population.

Concurrent Chagas’ disease and borderline disseminated cutaneous leishmaniasis: The role of amiodarone as an antitrypanosomatidae drug

PubMed Central

Paniz-Mondolfi, Alberto E; Pérez-Álvarez, Alexandra M; Reyes-Jaimes, Oscar; Socorro, Gustavo; Zerpa, Olga; Slova, Denisa; Concepción, Juan L

2008-01-01

The occurrence of mixed infections of Trypanosoma cruzi and Leishmania spp. is becoming a common feature in Central and South America due to overlapping endemic areas. Unfortunately, the possibilities for treating flagellated kinetoplastid infections are still very limited and most of the available drugs exhibit severe side effects. Although the development of new drugs for Leishmania has markedly improved in the last years, the tendency is still to employ antimonial compounds. On the other hand, treatment for Chagas’ disease is only available for the acute phase with no effective therapeutical options for chronic stage disease. The following case report substantiates the recently discovered effect of amiodarone as a nonconventional antiparasitic drug, particularly against Leishmania, breaching a new perspective in the therapeutic management of these important infectious parasitic diseases. PMID:18827865

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.

The effect of amiodarone on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population.

PubMed

Holm, J; Lindh, J D; Andersson, M L; Mannheimer, B

2017-03-01

Essentials Data on the effect of introducing amiodarone in patients already using warfarin regime are scarce. Information on 754 patients was extracted from three nationwide registers in Sweden. With amiodaron, 37% of patients had an international normalized ratio (INR) over 3.0 To avoid bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring. Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as co-medication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. Objectives An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nationwide registries. Patients/Methods In a retrospective cohort study including 754 patients, warfarin doses were compared between two 4-week periods, before and 18-21 weeks after initiating co-treatment with amiodarone. In addition, warfarin doses and international normalized ratio (INR) values were calculated week-by-week after the initiation of amiodarone. Results The initiation of amiodarone increased the mean INR from 2.6 to 3.1. The proportion of patients with a supratherapeutic INR over 3.0 and 4.0 increased from 12% to 37% and 0.9% to 5.5%, respectively. The subsequent mean decrease in warfarin dose was 24.6% (95% confidence interval [CI], 23.5, 25.6). The frequency of INR monitoring within 1 and 2 weeks after initiation of amiodarone was 67% and 90%. Conclusions Although warfarin doses in most patients were within the therapeutic range, more than one in three patients initiating co-treatment with amiodarone were exposed to a supratherapeutic anticoagulative effect within 3 weeks. In order to further avoid severe unnecessary bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring, anticipating an average dose reduction of 25%. © 2017 International Society on Thrombosis and Haemostasis.

Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA)

PubMed

Doval, H C; Nul, D R; Grancelli, H O; Perrone, S V; Bortman, G R; Curiel, R

1994-08-20

In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias. The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure. Our prospective multicentre trial included 516 patients on optimal standard treatment for heart failure. Patients were randomised to 300 mg/day amiodarone (260) or to standard treatment (256). Intention-to-treat analysis showed 87 deaths in the amiodarone group (33.5%) compared with 106 in the control group (41.4%) (risk reduction 28%; 95% CI 4%-45%; log rank test p = 0.024). There were reductions in both sudden death (risk reduction 27%; p = 0.16) and death due to progressive heart failure (risk reduction 23%; p = 0.16). Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure (119 versus 149 in the control group; risk reduction 31%; 95% CI 13-46%; p = 0.0024). The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia. Side-effects were reported in 17 patients (6.1%); amiodarone was withdrawn in 12. Low-dose amiodarone proved to be an effective and reliable treatment, reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias.

Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.

PubMed

Giannattasio, Francesco; Salvio, Antonio; Varriale, Maria; Picciotto, Francesco Paolo; Di Costanzo, Giovan Giuseppe; Visconti, Mario

2002-01-01

Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.

Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2014-01-01

Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

In vitro anti-Trypanosoma cruzi activity of dronedarone, a novel amiodarone derivative with an improved safety profile.

PubMed

Benaim, Gustavo; Hernandez-Rodriguez, Vanessa; Mujica-Gonzalez, Sheira; Plaza-Rojas, Lourdes; Silva, May Li; Parra-Gimenez, Nereida; Garcia-Marchan, Yael; Paniz-Mondolfi, Alberto; Uzcanga, Graciela

2012-07-01

Amiodarone, a commonly used antiarrhythmic, is also a potent and selective anti-Trypanosoma cruzi agent. Dronedarone is an amiodarone derivative in which the 2,5-diiodophenyl moiety of the parental drug has been replaced with an unsubstituted phenyl group aiming to eliminate the thyroid toxicity frequently observed with amiodarone treatment. Dronedarone has been approved by the Food and Drug Administration (FDA), and its use as a safe antiarrhythmic has been extensively documented. We show here that dronedarone also has potent anti-T. cruzi activity, against both extracellular epimastigotes and intracellular amastigotes, the clinically relevant form of the parasite. The 50% inhibitory concentrations against both proliferative stages are lower than those previously reported for amiodarone. The mechanism of action of dronedarone resembles that of amiodarone, as it induces a large increase in the intracellular Ca(2+) concentration of the parasite, which results from the release of this ion from intracellular storage sites, including a direct effect of the drug on the mitochondrial electrochemical potential, and through alkalinization of the acidocalcisomes. Our results suggest a possible future repurposed use of dronedarone for the treatment of Chagas' disease.

Minimally Invasive Delivery of Hydrogel-Encapsulated Amiodarone to the Epicardium Reduces Atrial Fibrillation.

PubMed

Garcia, Jose R; Campbell, Peter F; Kumar, Gautam; Langberg, Jonathan J; Cesar, Liliana; Deppen, Juline N; Shin, Eric Y; Bhatia, Neal K; Wang, Lanfang; Xu, Kai; Schneider, Frank; Robinson, Brian; García, Andrés J; Levit, Rebecca D

2018-05-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter. Implantation of amiodarone-containing gel significantly reduced the duration of sustained AF at 21 and 28 days; inducibility of AF was reduced 14 and 21 days post-delivery. Off-target organ drug levels in the liver, lungs, thyroid, and fat were significantly reduced in animals treated with epicardial amiodarone gel compared with systemic controls in small-animal distribution studies. The pericardium is an underutilized therapeutic site and may be a new treatment strategy for AF and other cardiovascular diseases. © 2018 American Heart Association, Inc.

Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

PubMed

Oryan, A; Bemani, E; Bahrami, S

2018-04-22

Leishmaniasis is a group of human and animal diseases causing 20,000-40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

PubMed

White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

2016-03-01

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

Amiodarone and Catheter Ablation as Cardiac Resynchronization Therapy for Children with Dilated Cardiomyopathy and Wolff-Parkinson-White Syndrome

PubMed Central

Kim, Sung Hoon; Jeong, Soo In; Kang, I-Seok; Lee, Heung Jae

2013-01-01

Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children. PMID:23407697

Amiodarone in the treatment of refractory supraventricular and ventricular arrhythmias

PubMed Central

Wheeler, P. J.; Ingram, D. V.; Puritz, R.; Chamberlain, D. A.

1979-01-01

Amiodarone is an antiarrhythmic agent unrelated to other drugs in current use. It has been little used in Britain, and no formal clinical trials have been possible because the drug has not been licensed by the Committee on Safety of Medicines. Nevertheless it has unique properties which can be valuable in the treatment of a wide spectrum of arrhythmias, particularly supraventricular tachycardias. Amiodarone has a slow onset of action and is cumulative. A sustained action is therefore achieved without the need for frequent maintenance dosage. Fifty patients have been treated with amiodarone in maintenance doses ranging from 200 mg on alternate days to 200 mg twice daily either alone, or in combination with conventional therapy. All were resistant to conventional therapy alone or could not be treated with usual agents because of unwanted drug effects. Of 27 patients with supraventricular arrhythmias, 18 were completely controlled and the other 9 were markedly improved. Six of 8 patients with recurrent life-threatening ventricular arrhythmias were well controlled symptomatically. Results were predictably less satisfactory in 15 high risk post-infarction patients with malignant arrhythmias and severe myocardial damage, but 6 were probably improved as a result of amiodarone. All patients on maintenance therapy for 3 months or more developed corneal microdeposits. None has any visual symptoms or other ocular defect, and treatment has not been curtailed as a result of this well recognized effect which is believed to be reversible and benign. Amiodarone can control patients with otherwise refractory arrhythmias including some which are life-threatening. Formal clinical trials are needed to define accurately its future role in the prevention and treatment of serious rhythm disorders of the heart. PMID:432163

Amiodarone affects Ebola virus binding and entry into target cells.

PubMed

Salata, Cristiano; Munegato, Denis; Martelli, Francesco; Parolin, Cristina; Calistri, Arianna; Baritussio, Aldo; Palù, Giorgio

2018-03-02

Ebola Virus Disease is one of the most lethal transmissible infections characterized by a high fatality rate. Several research studies have aimed to identify effective antiviral agents. Amiodarone, a drug used for the treatment of arrhythmias, has been shown to inhibit filovirus infection in vitro by acting at the early step of the viral replication cycle. Here we demonstrate that amiodarone reduces virus binding to target cells and slows down the progression of the viral particles along the endocytic pathway. Overall our data support the notion that amiodarone interferes with Ebola virus infection by affecting cellular pathways/targets involved in the viral entry process.

Effect of amiodarone-induced hyperthyroidism on left ventricular outflow obstruction after septal myectomy for hypertrophic cardiomyopathy.

PubMed

Pokorney, Sean D; Stone, Neil J; Passman, Rod; Oyer, David; Rigolin, Vera H; Bonow, Robert O

2010-12-01

Patients with obstructive hypertrophic cardiomyopathy who undergo septal myectomy are at risk for developing postoperative atrial fibrillation. Amiodarone is effective in treating this arrhythmia but is associated with multiple adverse effects, often with delayed onset. A novel case is described of a patient who developed type 2 amiodarone-induced hyperthyroidism that presented as recurrence of outflow obstruction after septal myectomy. The patient's symptoms and echocardiographic findings of outflow obstruction resolved substantially with the treatment of the amiodarone-induced hyperthyroidism. Amiodarone-induced hyperthyroidism of delayed onset can be a subtle diagnosis, requiring a high index of suspicion. In conclusion, recognition of this diagnosis in patients with recurrence of outflow obstruction by symptoms and cardiac imaging after septal myectomy may avoid unnecessary repeat surgical intervention. Copyright © 2010 Elsevier Inc. All rights reserved.

Amiodarone Versus Lidocaine for Pediatric Cardiac Arrest Due to Ventricular Arrhythmias: A Systematic Review.

PubMed

McBride, Mary E; Marino, Bradley S; Webster, Gregory; Lopez-Herce, Jesús; Ziegler, Carolyn P; De Caen, Allan R; Atkins, Dianne L

2017-02-01

We performed a systematic review as part of the International Liaison Committee on Resuscitation process to create a consensus on science statement regarding amiodarone or lidocaine during pediatric cardiac arrest for the 2015 International Liaison Committee on Resuscitation's Consensus on Science and Treatment Recommendations. Studies were identified from comprehensive searches in PubMed, Embase, and the Cochrane Library. Studies eligible for inclusion were randomized controlled and observational studies on the relative clinical effect of amiodarone or lidocaine in cardiac arrest. Studies addressing the clinical effect of amiodarone versus lidocaine were extracted and reviewed for inclusion and exclusion criteria by the reviewers. Studies were rigorously analyzed thereafter. We identified three articles addressing lidocaine versus amiodarone in cardiac arrest: 1) a prospective study assessing lidocaine versus amiodarone for refractory ventricular fibrillation in out-of-hospital adults; 2) an observational retrospective cohort study of inpatient pediatric patients with ventricular fibrillation or pulseless ventricular tachycardia who received lidocaine, amiodarone, neither or both; and 3) a prospective study of ventricular tachycardia with a pulse in adults. The first study showed a statistically significant improvement in survival to hospital admission with amiodarone (22.8% vs 12.0%; p = 0.009) and a lack of statistical difference for survival at discharge (p = 0.34). The second article demonstrated 44% return of spontaneous circulation for amiodarone and 64% for lidocaine (odds ratio, 2.02; 1.36-3.03) with no statistical difference for survival at hospital discharge. The third article demonstrated 48.3% arrhythmia termination for amiodarone versus 10.3% for lidocaine (p < 0.05). All were classified as lower quality studies without preference for one agent. The confidence in effect estimates is so low that International Liaison Committee on Resuscitation felt that a recommendation to use of amiodarone over lidocaine is too speculative; we suggest that amiodarone or lidocaine can be used in the setting of pulseless ventricular tachycardia/ventricular fibrillation in infants and children.

Acute amiodarone promotes drift and early termination of spiral wave re-entry.

PubMed

Nakagawa, Harumichi; Honjo, Haruo; Ishiguro, Yuko S; Yamazaki, Masatoshi; Okuno, Yusuke; Harada, Masahide; Takanari, Hiroki; Sakuma, Ichiro; Kamiya, Kaichiro; Kodama, Itsuo

2010-07-01

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 microM) caused prolongation of action potential duration (APD) by 5.6%-9.1%, whereas lidocaine (15 microM) caused APD shortening by 5.0%-6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.

2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction.

PubMed

Bartalena, Luigi; Bogazzi, Fausto; Chiovato, Luca; Hubalewska-Dydejczyk, Alicja; Links, Thera P; Vanderpump, Mark

2018-03-01

Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

Evaluation of the Hemodynamic Effects of Intravenous Amiodarone Formulations During the Maintenance Phase Infusion.

PubMed

Lindquist, Desirae E; Rowe, A Shaun; Heidel, Eric; Fleming, Travis; Yates, John R

2015-12-01

Two of the excipients in intravenous formulations of amiodarone, polysorbate 80 and benzyl alcohol, have been shown to cause hypotension. A newer formulation of amiodarone, which contains cyclodextrin, is devoid of these excipients. To evaluate the change in mean arterial pressure when utilizing 2 intravenous amiodarone formulations. This was a retrospective cohort analysis conducted at an academic medical center. Patients received intravenous amiodarone containing either polysorbate 80/benzyl alcohol (control) or cyclodextrin (cyclodextrin). Patients received these formulations based on a standard institutional protocol of 1 mg/min for 6 hours, followed by 0.5 mg/min for at least 18 hours or until discontinued by the provider. All data were collected from the medical record and included changes in blood pressures, time to lowest systolic blood pressure, concurrent antihypertensive use, and number of patients requiring treatment for hypotension. A total of 160 patients (120 control, 40 cyclodextrin) were included. There was a statistically significant difference in mean arterial pressure between the groups receiving the control formulation of amiodarone compared with the cyclodextrin formulation across the 24-hour maintenance phase infusion (P < 0.001). There was a significant difference between formulations with regard to the change in mean arterial pressure during the 0- to 6-hour and 12- to 18-hour time blocks. There was a statistically significant difference in the number of patients receiving fluid boluses for treatment of hypotension (P = 0.001). The excipients in the formulation of intravenous amiodarone may have a significant role in the hypotensive effects seen throughout the duration the maintenance phase infusion. © The Author(s) 2015.

Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells.

PubMed

Sato, Toshiaki; Takizawa, Taichi; Saito, Tomoaki; Kobayashi, Satoru; Hara, Yukio; Nakaya, Haruaki

2003-12-01

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.

Severe congestive heart failure patient on amiodarone presenting with myxedemic coma: a case report.

PubMed

Shaheen, Mazen

2009-01-01

This is a case report of myxedema coma secondary to amiodarone-induced hypothyroidism in a patient with severe congestive heart failure (CHF). To our knowledge and after reviewing the literature there is one case report of myxedema coma during long term amiodarone therapy. Myxedema coma is a life threatening condition that carries a mortality reaching as high as 20% with treatment. The condition is treated with intravenous thyroxine (T4) or intravenous tri-iodo-thyronine (T3). Patients with CHF on amiodarone may suffer serious morbidity and mortality from hypothyroidism, and thus may deserve closer follow up for thyroid stimulating hormone (TSH) levels. This case report carries an important clinical application given the frequent usage of amiodarone among CHF patients. The myriad clinical presentation of myxedema coma and its serious morbidity and mortality stresses the need to suspect this clinical syndrome among CHF patients presenting with hypotension, weakness or other unexplained symptoms.

Dronedarone for the treatment of atrial fibrillation and atrial flutter: approval and efficacy.

PubMed

Wolbrette, Deborah; Gonzalez, Mario; Samii, Soraya; Banchs, Javier; Penny-Peterson, Erica; Naccarelli, Gerald

2010-08-09

Dronedarone, a new Class III antiarrhythmic agent, has now been approved by the US Food and Drug Administration for use in patients with atrial fibrillation or atrial flutter. Approval came in March 2009 due to the positive results of the ATHENA trial showing significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. However, due to safety concerns in the heart failure population in the earlier ANDROMEDA trial, dronedarone is not recommended for patients with an ejection fraction <35% and recent decompensated heart failure. Dronedarone is an amiodarone analog with multichannel blocking electrophysiologic properties similar to those of amiodarone, but several structural differences. Dronedarone's lack of the iodine moiety reduces its potential for thyroid and pulmonary toxicity. Preliminary data from the DIONYSOS trial, and an indirect meta-analysis comparing amiodarone with dronedarone, showed amiodarone to be more effective in maintaining sinus rhythm, while dronedarone was associated with fewer adverse effects resulting in early termination of the drug. Dronedarone is the first antiarrhythmic drug for the treatment of atrial fibrillation and atrial flutter shown to reduce cardiovascular hospitalizations. In patients with structural heart disease who have an ejection fraction >35% and no recent decompensated heart failure, dronedarone should be considered earlier than amiodarone in the treatment algorithm.

Incidence and severity of phlebitis in patients receiving peripherally infused amiodarone.

PubMed

Boyce, Brenda A Brady; Yee, Barbara Homer

2012-08-01

Nurses noted that the rate of phlebitis was high when intravenous amiodarone was infused via a peripheral site. Hospital policy recommends a central vascular catheter, but this method is often not feasible because the drug is administered in emergent situations for short periods. To determine the rate and severity of phlebitis in patients given peripherally infused amiodarone. The literature, policy, and procedures for administration of amiodarone were reviewed; the pharmacy was consulted; and a data collection tool was developed. The tool was pilot tested and revised, and face validation was established. Data were collected during a 6-month period. A convenience sample was used. The study included a total of 12 patients. Each new infusion of intravenous amiodarone was considered a separate occurrence, for a total of 24 infusions. Various grades of phlebitis developed in 8 patients (67%). Phlebitis developed at 12 of the 24 infusion sites (50%). Patients receiving peripherally infused amiodarone are at high risk for phlebitis. This complication may lead to infection, additional medical intervention, delay in treatment, and prolonged hospitalization.

Efficacy and safety in pharmacological cardioversion of recent-onset atrial fibrillation: a propensity score matching to compare amiodarone vs class IC antiarrhythmic drugs.

PubMed

Bonora, Antonio; Turcato, Gianni; Franchi, Elena; Taioli, Gabriele; Dilda, Alice; Zerman, Germana; Maccagnani, Antonio; Pistorelli, Claudio; Olivieri, Oliviero

2017-09-01

The acute management of recent-onset (<48 h) atrial fibrillation (AF) is still debated. Aim of our study was to compare efficacy and safety of intravenously administered class IC antidysrhythmic agents vs amiodarone in a propensity score matched series of patients acutely treated for AF in the emergency department. During a 3-year period, we retrospectively evaluated all episodes of recent-onset (<48 h) AF pharmacologically treated for sinus rhythm restoration in the emergency department. By means of a propensity score matching considering the main statistically different covariates, we selected two accurately matched treatment groups. We analysed the differences between amiodarone and class IC group in terms of efficacy and safety that is conversion to sinus rhythm rates within 12 and 48 h after starting treatment, time to conversion, and adverse drug effects. An overall number of 817 episodes of recent-onset AF were collected (amiodarone group = 406, class IC group = 411). After matching, we obtained 358 episodes equally divided (amiodarone group = 179 and class IC group = 179). Conversion rates within 12 h were 139 (53.1 %) in amiodarone group and 95 (72.6 %) in class IC group (p < 0.05). Median time for cardioversion was 420 min (331.6-508.3 CI 95 %) in amiodarone and 55 min (44.9-65.1 CI 95 %) in class IC group (p < 0.05). The incidence of adverse events in both groups was very low and equally distributed (p = ns). Intravenously administration of class IC agents, when compared with amiodarone, proved to be more rapid and effective, and equally safe in the acute management of recent-onset AF.

Pulmonary hypertension and isolated right heart failure complicating amiodarone induced hyperthyroidism.

PubMed

Wong, Sean-Man; Tse, Hung-Fat; Siu, Chung-Wah

2012-03-01

Hyperthyroidism is a common side effect encountered in patients prescribed long-term amiodarone therapy for cardiac arrhythmias. We previously studied 354 patients prescribed amiodarone in whom the occurrence of hyperthyroidism was associated with major adverse cardiovascular events including heart failure, myocardial infarction, ventricular arrhythmias, stroke and even death [1]. We now present a case of amiodarone-induced hyperthyroidism complicated by isolated right heart failure and pulmonary hypertension that resolved with treatment of hyperthyroidism. Detailed quantitative echocardiography enables improved understanding of the haemodynamic mechanisms underlying the condition. Copyright © 2011 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.

A review of the pharmacokinetics, electrophysiology and clinical efficacy of dronedarone.

PubMed

Hynes, B John; Luck, Jerry C; Wolbrette, Deborah L; Khan, Mazhar; Naccarelli, Gerald V

2005-03-01

The results of major clinical trials and advances in pharmacologic and nonpharmacologic therapies are continuing to alter treatment approaches for both atrial and ventricular arrhythmias. Originally developed as an antianginal medication, amiodarone serves as the most effective antiarrhythmic drug in the treatment of both atrial and life-threatening ventricular arrhythmias. However, amiodarone has complex pharmacokinetics and is associated with serious extracardiac side effects, partially due to the presence of an iodine moiety. With a better understanding of the mechanisms of arrhythmias and antiarrhythmic drugs, new antiarrhythmic agents are currently under development with the hope that they will be more effective and safer than currently available drugs. One such drug that might potentially fulfill this hope is dronedarone. This amiodarone-like compound lacks the iodine moiety, and is similar in structure and electrophysiologic mechanisms of action to amiodarone, to date no evidence of liver, thyroid or pulmonary toxicity has been reported. Three clinical trials demonstrate efficacy in suppressing recurrences of atrial fibrillation and there is also evidence of a rate-slowing benefit during atrial fibrillation/flutter. However, the ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity Decrease (ANDROMEDA) study, performed in patients with left ventricular dysfunction, demonstrated excess noncardiac mortality in patients treated with dronedarone. Although effective in the treatment of atrial fibrillation, the future of this novel amiodarone-like drug remains uncertain until further clarification of the excess mortality in heart failure patients is better studied.

Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame?

PubMed

Petrou, Emmanouil; Iakovou, Ioannis; Boutsikou, Maria; Girasis, Chrysafios; Mavrogeni, Sophie; Pavlides, Gregory

2014-01-01

Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia. Copyright © 2014 Elsevier Inc. All rights reserved.

Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle?

PubMed Central

Rhodes, A; Eastwood, J B; Smith, S A

1993-01-01

A 72 year old white man developed acute hepatic impairment and renal failure within 24 hours of starting intravenous amiodarone for paroxysmal ventricular tachycardia. After normal initial investigations, there was a noticeable rise in serum transaminases as well as an increase in clotting times, a decrease in renal function and a thrombocytopenia. These changes returned to normal within seven days of withdrawal of the drug without specific treatment, and the patient was later treated with oral amiodarone without any further evidence of hepatotoxicity. Intravenous amiodarone has been implicated in acute hepatic disease on four previous occasions, but it is suggested that polysorbate 80, an organic surfactant added to the intravenous infusion, is a more likely cause of this complication. Similar reactions have been described with polysorbate 80 in association with the 'E-ferol' syndrome in infants. The occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth. PMID:8491409

Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle?

PubMed

Rhodes, A; Eastwood, J B; Smith, S A

1993-04-01

A 72 year old white man developed acute hepatic impairment and renal failure within 24 hours of starting intravenous amiodarone for paroxysmal ventricular tachycardia. After normal initial investigations, there was a noticeable rise in serum transaminases as well as an increase in clotting times, a decrease in renal function and a thrombocytopenia. These changes returned to normal within seven days of withdrawal of the drug without specific treatment, and the patient was later treated with oral amiodarone without any further evidence of hepatotoxicity. Intravenous amiodarone has been implicated in acute hepatic disease on four previous occasions, but it is suggested that polysorbate 80, an organic surfactant added to the intravenous infusion, is a more likely cause of this complication. Similar reactions have been described with polysorbate 80 in association with the 'E-ferol' syndrome in infants. The occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth.

Preoperative therapeutic apheresis for severe medically refractory amiodarone-induced thyrotoxicosis: a case report.

PubMed

Yamamoto, Jennifer; Dostmohamed, Hanifa; Schacter, Isanne; Ariano, Robert E; Houston, Donald S; Lewis, Brenda; Knoll, Colleen; Katz, Pamela; Zarychanski, Ryan

2014-06-01

Amiodarone is associated with thyroid dysfunction and life-threatening thyrotoxicosis. In medically refractory cases, or where medical therapy is contraindicated, thyroidectomy may be required. To decrease perioperative thyroid storm and to reduce overall surgical risk, apheresis may be considered preoperatively to restore euthyroidism. We report a 46-year-old female with a history of cardiac arrhythmia and tachycardia-induced cardiomyopathy for which she received amiodarone. Months after discontinuation of amiodarone, the patient presented with wide complex tachycardia and symptoms of thyrotoxicosis. Laboratory testing confirmed severe thyrotoxicosis which was subsequently refractory to medical therapy. Total thyroidectomy was required. Following a total of 10 apheresis treatments, thyroid hormone levels were reduced to near normal levels and the patient's symptoms improved. Thyroidectomy was performed without intraoperative or postoperative complication. In the setting of life-threatening, medically refractory amiodarone-induced thyrotoxicosis, therapeutic apheresis can effectively reduce thyroid hormone levels and restore a state of clinical and biochemical euthyroidism. © 2013 Wiley Periodicals, Inc.

Effects of injection-site splinting on the incidence of phlebitis in patients taking peripherally infused amiodarone: A randomized clinical trial.

PubMed

Ayat-Isfahani, Farah; Pashang, Mina; Davoudi, Bita; Sadeghian, Saeed; Jalali, Arash

2017-03-01

Intravenous amiodarone is considered an effective treatment option for cardiac ventricular and atrial arrhythmias. Peripheral infusion of amiodarone may cause blood vessels irritation and phlebitis that is the most common complication of this drug by this route even when it is administered within recommended dosing limits. The effect of injection-site splinting on the occurrence of phlebitis among a group of cardiac arrhythmia patients receiving peripherally infused amiodarone. This research is a clinical trial on patients of Tehran Heart Center who were hospitalized due to cardiac arrhythmias. A sample of 60 patients with mean age 65 ± 14 years were randomly divided into control and test groups. In the experimental group with close splint and restrict the movement of the injection site until the end of the infusion and control groups without closing brace, at the same time received amiodarone. Injection protocol was similar for both groups. The results were analyzed with Spss18. The results of this research still significantly reduced the incidence of amiodarone injection-site phlebitis in the injection time (P = .005). Copyright © 2016 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.

Adverse effects of oral amiodarone therapy.

PubMed

Sinha, P R; Dube, S; Sujata; Gupta, P R; Avasthey, P; Somani, P N

1992-04-01

Oral amiodarone was administered to 38 patients (25 males, 13 females) with mean age of 43.6 years. Ventricular and supraventricular arrhythmias were present in 30 and 8 patients respectively. Amiodarone was given as 400-1200 mg/day for 1-2 weeks as loading dose and then it was maintained as 100-600 mg/day. The mean duration of therapy was 12.4 months. Adverse effects were noted in 21 (55.3%) cases. The commonest adverse effects observed were asymptomatic corneal microdeposits followed by gastrointestinal, cardiac, neurological and cutaneous disturbances. The drug was withdrawn in 2 (5.3%) patients because of nausea and vomiting. One patient died of pulmonary infiltrations. It is concluded that adverse effects are common with amiodarone but are tolerated well, making this drug an excellent choice for treatment of cardiac arrhythmias.

Amiodarone-associated bilateral vestibulopathy.

PubMed

Gürkov, Robert; Manzari, Leonardo; Blödow, Alexander; Wenzel, Angela; Pavlovic, Dusan; Luis, Leonal

2018-03-01

Bilateral vestibulopathy (BVP) is a debilitating disorder characterized by the hypofunction of both vestibular end organs or nerves. The most frequent identifiable causes of BVP are ototoxic drug effects, infectious and autoimmune disorders. The majority of cases, however, remain idiopathic. Medical records of patients diagnosed with idiopathic BVP were examined in five dizziness clinics. We identified 126 patients with "idiopathic" BVP. Out of these, 15 patients had a history of Amiodarone treatment before the diagnosis of BVP, resulting in a 12% prevalence. The present report supports the hypothesis that Amiodarone can cause BVP. Vestibular examination in patients taking Amiodarone and suffering from balance-related symptoms are recommended, to recognize this adverse effect as early as possible and allow for an informed judgement on a potential dose reduction or withdrawal for recovery of the vestibular function.

Heart rate is a marker of amiodarone mortality reduction in severe heart failure. The GESICA-GEMA Investigators. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina-Grupo de Estudios Multicéntricos en Argentina.

PubMed

Nul, D R; Doval, H C; Grancelli, H O; Varini, S D; Soifer, S; Perrone, S V; Prieto, N; Scapin, O

1997-05-01

The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction < 35%) In the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up. Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival. The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR > or = 90 beats/min (control: n = 132; amiodarone: n = 122) and < 90 beats/min (control: n = 124; amiodarone: n = 138). Survival was also analyzed according to heart rate reduction at 6 months for 367 patients. For patients with a BHR > or = 90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p < 0.002). Both sudden death (RR 0.46, 95% CI 0.24 to 0.90, p < 0.02) and progressive heart failure death (RR 0.60, 95% CI 0.30 to 1.03, p < 0.06) were reduced, and functional capacity was improved. In patients with a BHR < 90 beats/min, amiodarone did not alter survival. Among 367 patients who completed 6 months of follow-up, amiodarone reduced 2-year mortality only in those with a BHR > or = 90 beats/min, which was reduced at 6 months. Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.

The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry.

PubMed

Gehring, Gerrit; Rohrmann, Katrin; Atenchong, Nkacheh; Mittler, Eva; Becker, Stephan; Dahlmann, Franziska; Pöhlmann, Stefan; Vondran, Florian W R; David, Sascha; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

2014-08-01

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds. We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant. The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hepatotoxicity After Continuous Amiodarone Infusion in a Postoperative Cardiac Infant

PubMed Central

Kicker, Jennifer S.; Haizlip, Julie A.; Buck, Marcia L.

2012-01-01

A former 34-week-old female infant with Down syndrome underwent surgical correction of a congenital heart defect at 5 months of age. Her postoperative course was complicated by severe pulmonary hypertension and junctional ectopic tachycardia. Following treatment with amiodarone infusion, she developed laboratory indices of acute liver injury. At their peak, liver transaminase levels were 19 to 35 times greater than the upper limit of normal. Transaminitis was accompanied by coagulopathy, hyperammonemia, and high serum lactate and lipid levels. Hepatic laboratory abnormalities began to resolve within 48 hr of stopping amiodarone infusion. Heart rate control was achieved concurrently with discovery of laboratory test result abnormalities, and no further antiarrhythmic therapy was required. The intravenous formulation of amiodarone contains the diluent polysorbate 80, which may have hepatotoxic effects. Specifically, animal studies suggest that polysorbate 80 may destabilize cell membranes and predispose to fatty change within liver architecture. Polysorbate was implicated in infant fatalities from E-ferol use in the 1980s. This case illustrates a possible adverse event by the Naranjo probability scale. Given the extent of clinically apparent hepatic injury, this patient was not rechallenged with amiodarone during the remainder of her hospitalization. With amiodarone now used as first-line pharmacologic therapy for critical tachyarrhythmia in this population, the number of children exposed to this drug should be expected to increase. Laboratory indices of liver function should be evaluated at initiation of amiodarone therapy, as well as frequently throughout duration of therapy. Consideration should be given to polysorbate-free formulation of intravenous amiodarone for use in the cohort with congenital cardiac disease. PMID:23118673

Hepatotoxicity after continuous amiodarone infusion in a postoperative cardiac infant.

PubMed

Kicker, Jennifer S; Haizlip, Julie A; Buck, Marcia L

2012-04-01

A former 34-week-old female infant with Down syndrome underwent surgical correction of a congenital heart defect at 5 months of age. Her postoperative course was complicated by severe pulmonary hypertension and junctional ectopic tachycardia. Following treatment with amiodarone infusion, she developed laboratory indices of acute liver injury. At their peak, liver transaminase levels were 19 to 35 times greater than the upper limit of normal. Transaminitis was accompanied by coagulopathy, hyperammonemia, and high serum lactate and lipid levels. Hepatic laboratory abnormalities began to resolve within 48 hr of stopping amiodarone infusion. Heart rate control was achieved concurrently with discovery of laboratory test result abnormalities, and no further antiarrhythmic therapy was required. The intravenous formulation of amiodarone contains the diluent polysorbate 80, which may have hepatotoxic effects. Specifically, animal studies suggest that polysorbate 80 may destabilize cell membranes and predispose to fatty change within liver architecture. Polysorbate was implicated in infant fatalities from E-ferol use in the 1980s. This case illustrates a possible adverse event by the Naranjo probability scale. Given the extent of clinically apparent hepatic injury, this patient was not rechallenged with amiodarone during the remainder of her hospitalization. With amiodarone now used as first-line pharmacologic therapy for critical tachyarrhythmia in this population, the number of children exposed to this drug should be expected to increase. Laboratory indices of liver function should be evaluated at initiation of amiodarone therapy, as well as frequently throughout duration of therapy. Consideration should be given to polysorbate-free formulation of intravenous amiodarone for use in the cohort with congenital cardiac disease.

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

PubMed

Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

1998-01-01

Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p < 0.001) in the heart rate values in comparison with diabetic patients, in whom a significant decrease (p < 0.001) was found only at the 4th day. A significant (p = 0.0004), more rapid onset of the antiarrhythmic response to the drug was found in nondiabetic patients (6.8 +/- 6.0 h) in comparison with diabetic patients (98.0 +/- 14.8 h). Our findings suggest that the antiarrhythmic effects of amiodarone in diabetic patients with uncontrolled atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

Recovery From Amiodarone-Induced Cornea Verticillata by Application of Topical Heparin.

PubMed

Frings, Andreas; Schargus, Marc

2017-11-01

To report a case of amiodarone-induced vortex keratopathy-associated anatomical findings and subjective visual perception before and after treatment with topical heparin eye drops. Case report. A 76-year-old man complained of halos in his vision in both his eyes due to prominent bilateral cornea verticillata. For treatment of cornea verticillata, we prescribed unpreserved eye drops of a sterile, phosphate-free solution of 0.1% sodium hyaluronate with 1300 IU/mL heparin sodium 3 times daily to the left eye, whereas the other side served as the control. The area of corneal deposits was measured by 2 examiners before and at the 1- and 3-month examination. At last follow-up, cornea verticillata had been reduced from 6 to 2 mm in area by approximately 66% from grade-III to grade-II amiodarone keratopathy. In patients using amiodarone, clearing of cornea verticillata may be achieved by topical use of unpreserved eye drops of a sterile, phosphate-free solution of 0.1% sodium hyaluronate with 1300 IU/mL heparin sodium.

Preclinical evaluation of amiodarone for the treatment of murine leukemia P388. In vivo and in vitro investigation.

PubMed

Papageorgiou, A D; Dalezis, P; Mourelatos, C; Lioutas, K; Sahpazidou, D; Geromichalou, E; Geromichalos, G; Lialiaris, Th; Athanasiadou, P; Athanasiadis, P

2010-01-01

The purpose of the present study was the investigation of antileukemic effect of amiodarone in leukemia P388 BDF1 bearing mice and its genotoxic and cytostatic effect in cultured normal human lymphocytes. Leukemia P388 was used in this study. BDF1 mice were used for chemotherapy evaluation in vivo. The antitumor activity was assessed by the oncostatic parameter T/C, representing the increase of life span of drug-treated animals vs. controls. Lymphocyte cultures were used to study the genotoxic and cytostatic effect in vitro, expressed by enhanced sister chromatid exchange (SCE) and reduced proliferation rate indices (PRIS). Amiodarone was found to exert antileukemic potency against leukemia P388 bearing mice at all three different treatment schedules used, yielding T/C values of 155%, 163% with one cure and 230%. In the in vitro cytogenic experiments, significant increase of SCE rates by amiodarone was observed at 0.2 μM, while at the same concentration significant suppression of PRIS was achieved. According to the National Cancer Institute (NCI), a compound is characterized as potential chemotherapeutic deserving further evaluation if it produces T/C values≥125%. On the other hand the SCE assay has predictive value as a clinical assay for drugs exhibiting a strong correlation between cell killing and induction of SCEs. Further studies are warranted to clarify the structure-activity relationship of amiodarone.

[Thyroid hormones and cardiovascular system].

PubMed

Límanová, Zdeňka; Jiskra, Jan

Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans.

PubMed

Gamarra, Soledad; Rocha, Elousa Maria F; Zhang, Yong-Qiang; Park, Steven; Rao, Rajini; Perlin, David S

2010-05-01

The antiarrhythmic drug amiodarone has been found to have fungicidal activity. In Saccharomyces cerevisiae, its antifungal activity is mediated by calcium overload stress, which leads to a rapid nuclear accumulation of the calcineurin-regulated transcription factor CRZ1. In addition, low doses of amiodarone have been reported to be synergistic with fluconazole in fluconazole-resistant Candida albicans. To establish its mechanism of toxicity in C. albicans, we used expression profiling of key pathway genes to examine cellular responses to amiodarone alone and in combination with fluconazole. Gene expression profiling of 59 genes was done in five C. albicans strains (three fluconazole-susceptible strains and two fluconazole-resistant strains) after amiodarone and/or fluconazole exposure. Of the 59 genes, 27 analyzed showed a significant change (>2-fold) in expression levels after amiodarone exposure. The up- or downregulated genes included genes involved in Ca(2+) homeostasis, cell wall synthesis, vacuolar/lysosomal transport, diverse pathway regulation, stress response, and pseudohyphal morphogenesis. As expected, fluconazole induces an increase in ergosterol pathway genes expression levels. The combination treatment significantly dampened the transcriptional response to either drug, suggesting that synergism was due to an inhibition of compensatory response pathways. This dampening resulted in a decrease in total ergosterol levels and decreased pseudohyphal formation, a finding consistent with decreased virulence in a murine candidiasis model.

Phlebitis in amiodarone administration: incidence, contributing factors, and clinical implications.

PubMed

Norton, Linda; Ottoboni, Linda K; Varady, Ann; Yang-Lu, Chia-Yu; Becker, Nancy; Cotter, Theresa; Pummer, Eileen; Haynes, Annette; Forsey, Lynn; Matsuda, Kelly; Wang, Paul

2013-11-01

Intravenous amiodarone is an important treatment for arrhythmias, but peripheral infusion is associated with direct irritation of vessel walls and phlebitis rates of 8% to 55%. Objectives To determine the incidence and factors contributing to the development of amiodarone-induced phlebitis in the coronary care unit in an academic medical center and to refine the current practice protocol. Medical records from all adult patients during an 18-month period who received intravenous amiodarone while in the critical care unit were reviewed retrospectively. Route of administration, location, concentration, and duration of amiodarone therapy and factors associated with occurrence of phlebitis were examined. Descriptive statistics and regression methods were used to identify incidence and phlebitis factors. In the final sample of 105 patients, incidence of phlebitis was 40%, with a 50% recurrence rate. All cases of phlebitis occurred in patients given a total dose of 3 g via a peripheral catheter, and one-quarter of these cases (n = 10) developed at dosages less than 1 g. Pain, redness, and warmth were the most common indications of phlebitis. Total dosage given via a peripheral catheter, duration of infusion, and number of catheters were significantly associated with phlebitis. Amiodarone-induced phlebitis occurred in 40% of this sample at higher drug dosages. A new practice protocol resulted from this study. An outcome study is in progress.

Management of amiodarone extravasation with intradermal hyaluronidase.

PubMed

Fox, Ashley N; Villanueva, Ruben; Miller, Jamie L

2017-10-01

The case of a patient who experienced extravasation while receiving amiodarone via a peripheral infusion and was treated with intradermal hyaluronidase is reported. A 60-year-old Caucasian man arrived at the emergency department after a motor vehicle collision. The patient was noted to have a subdural hematoma, multiple rib fractures, sternal body fracture, abdominal wall injury, left clavicle fracture, right humerus fracture, and vertebral fractures. His medical history included hypertension, atrial fibrillation, and stroke with residual right-sided weakness. On postoperative day 1, the patient developed atrial fibrillation and was started on i.v. amiodarone. Treatment resulted in conversion to sinus rhythm, but the patient again developed atrial fibrillation on postoperative day 5. During the morning hours of postoperative day 6, the patient experienced a peripheral i.v. line extravasation of amiodarone in his left arm. The amiodarone drip was discontinued, and amiodarone 400 mg orally twice daily was started. The nursing staff was instructed to treat the patient for the amiodarone extravasation with traditional nonpharmacologic measures, including warm compresses and elevation of the extremity. After extravasation, the patient reported severe pain at the site. Due to the patient's continued complaints of pain and the expanding area of induration, the interdisciplinary team elected to proceed with intradermal hyaluronidase. The patient reported significantly decreased pain and was discharged to inpatient rehabilitation on postoperative day 10 without any significant adverse effects. Administration of intradermal hyaluronidase after amiodarone extravasation was associated with decreased expansion of erythema and warmth as well as an improvement in patient-reported pain scores without any noted adverse effects. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulse less ventricular tachycardia or ventricular fibrillation☆

PubMed Central

Valdes, Santiago O.; Donoghue, Aaron J.; Hoyme, Derek B.; Hammond, Rachel; Berg, Marc D.; Berg, Robert A.; Samson, Ricardo A.

2015-01-01

Aim To determine the association between amiodarone and lidocaine and outcomes in children with cardiac arrest with pulse less ventricular tachycardia (pVT) and ventricular fibrillation (VF). Background Current AHA guidelines for CPR and emergency cardiovascular care recommend amiodarone for cardiac arrest in children associated with shock refractory pVT/VF, based on a single pediatric study and extrapolation from adult data. Methods Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients< 18 years old with pVT/VF cardiac arrest were included. Patients receiving amiodarone or lidocaine prior to arrest or whose initial arrest rhythm was unknown were excluded. Univariate analysis was performed to assess the association between patient and event factors and clinical outcomes. Multivariate analysis was performed to address independent association between lidocaine and amiodarone use and outcomes. Results Of 889 patients. 171 (19%) received amiodarone, 295 (33%) received lidocaine. and 82 (10%) received both. Return of spontaneous circulation (ROSC) occurred in 484/889 (54%), 24-h survival in 342/874 (39%), and survival to hospital discharge in 194/889 (22%}. Lidocaine was associated with improved ROSC (adjusted OR 2.02, 95% Cl 1.36-3 ). and 24-h survival (adjusted OR 1.66, 95% CI 1.11-2.49), but not hospital discharge. Amiodarone use was not associated with ROSC, 24 h survival, or survival to discharge. Conclusions For children with in-hospital pVT/VF, lidocaine use was independently associated with improved ROSC and 24-h survival. Amiodarone use was not associated with superior rates of ROSC, survival at 24 h. Neither drug was associated with survival to hospital discharge. PMID:24361455

Effect of prophylactic amiodarone on clinical and economic outcomes after cardiothoracic surgery: a meta-analysis.

PubMed

Gillespie, Effie L; Coleman, Craig I; Sander, Stephen; Kluger, Jeffrey; Gryskiewicz, Kristen A; White, C Michael

2005-09-01

Two previous meta-analyses of amiodarone for prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not evaluate total hospital cost, concluded that data on stroke are incomplete, and did not evaluate the effect of clinical heterogeneity between trials. To conduct a meta-analysis examining amiodarone's prophylactic impact on cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs. Three reviewers conducted a systematic literature search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were included if they met the following criteria: (1) randomized controlled trial versus placebo/routine treatment, (2) coronary artery bypass graft and/or valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Fifteen trials were identified, including 1512 and 1429 patients in the amiodarone and control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to 0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6) (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar 1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route of administration, use of a fixed-effects model, or exclusion of unblinded/unpublished studies did not affect the overall results. No statistical heterogeneity was observed for any endpoint evaluated (p > 0.22 for all comparisons). Prophylactic treatment with amiodarone decreases patients' risk of POAF and stroke while reducing LOS.

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

PubMed

Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

2015-12-25

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism of the Synergistic Effect of Amiodarone and Fluconazole in Candida albicans▿ †

PubMed Central

Gamarra, Soledad; Rocha, Elousa Maria F.; Zhang, Yong-Qiang; Park, Steven; Rao, Rajini; Perlin, David S.

2010-01-01

The antiarrhythmic drug amiodarone has been found to have fungicidal activity. In Saccharomyces cerevisiae, its antifungal activity is mediated by calcium overload stress, which leads to a rapid nuclear accumulation of the calcineurin-regulated transcription factor CRZ1. In addition, low doses of amiodarone have been reported to be synergistic with fluconazole in fluconazole-resistant Candida albicans. To establish its mechanism of toxicity in C. albicans, we used expression profiling of key pathway genes to examine cellular responses to amiodarone alone and in combination with fluconazole. Gene expression profiling of 59 genes was done in five C. albicans strains (three fluconazole-susceptible strains and two fluconazole-resistant strains) after amiodarone and/or fluconazole exposure. Of the 59 genes, 27 analyzed showed a significant change (>2-fold) in expression levels after amiodarone exposure. The up- or downregulated genes included genes involved in Ca2+ homeostasis, cell wall synthesis, vacuolar/lysosomal transport, diverse pathway regulation, stress response, and pseudohyphal morphogenesis. As expected, fluconazole induces an increase in ergosterol pathway genes expression levels. The combination treatment significantly dampened the transcriptional response to either drug, suggesting that synergism was due to an inhibition of compensatory response pathways. This dampening resulted in a decrease in total ergosterol levels and decreased pseudohyphal formation, a finding consistent with decreased virulence in a murine candidiasis model. PMID:20194694

Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone.

PubMed

Murata, Hiroshige; Miyauchi, Yasushi; Hayashi, Meiso; Iwasaki, Yu-Ki; Yodogawa, Kenji; Ueno, Akira; Hayashi, Hiroshi; Tsuboi, Ippei; Uetake, Shunsuke; Takahashi, Kenta; Yamamoto, Teppei; Maruyama, Mitsunori; Akutsu, Koichi; Yamamoto, Takeshi; Kobayashi, Yoshinori; Tanaka, Keiji; Atarashi, Hirotsugu; Katoh, Takao; Shimizu, Wataru

2015-01-01

Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation.

Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease--a cohort study.

PubMed

Stan, Marius N; Ammash, Naser M; Warnes, Carole A; Brennan, Michael D; Thapa, Prabin; Nannenga, Michael R; Bahn, Rebecca S

2013-08-10

Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD. At a tertiary care center we followed a historical cohort of amiodarone-treated CHD patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with last thyroid assessment on amiodarone. Cumulative incidence of AIT was calculated. AIT association with nutritional status was hypothesized a priori. AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO initiation compared with the rest of the cohort (mean ± standard deviation: 21.9 ± 2.9 vs. 25.1 ± 5.0; p<0.001). Patients with BMI<21 were more likely to develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%, p=0.059). On multivariate analysis body mass index and goiter remained independent predictors of outcome. BMI<21 at initiation of amiodarone therapy and presence of goiter are strong predictors of AIT in this population. Its incidence is time dependent. These predictors can be used clinically in assessing overall impact of amiodarone therapy in congenital heart disease patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Impact of dronedarone in atrial fibrillation and flutter on stroke reduction.

PubMed

Christiansen, Christine Benn; Torp-Pedersen, Christian; Køber, Lars

2010-04-07

Dronedarone has been developed for treatment of atrial fibrillation (AF) or atrial flutter (AFL). It is an amiodarone analogue but noniodinized and without the same adverse effects as amiodarone. This is a review of 7 studies (DAFNE, ADONIS, EURIDIS, ATHENA, ANDROMEDA, ERATO and DIONYSOS) on dronedarone focusing on efficacy, safety and prevention of stroke. There was a dose-finding study (DAFNE), 3 studies focusing on maintenance of sinus rhythm (ADONIS, EURIDIS and DIONYSOS), 1 study focusing on rate control (ERATO) and 2 studies investigating mortality and morbidity (ANDROMEDA and ATHENA). The target dose for dronedarone was established in the DAFNE study to be 400 mg twice daily. Both EURIDIS and ADONIS studies demonstrated that dronedarone was superior to placebo for maintaining sinus rhythm. However, DIONYSOS found that dronedarone is less efficient at maintaining sinus rhythm than amiodarone. ERATO concluded that dronedarone reduces ventricular rate in patients with chronic AF. The ANDROMEDA study in patients with severe heart failure was discontinued because of increased mortality in dronedarone group. Dronedarone reduced cardiovascular hospitalizations and mortality in patients with AF or AFL in the ATHENA trial. Secondly, according to a post hoc analysis a significant reduction in stroke was observed (annual rate 1.2% on dronedarone vs 1.8% on placebo, respectively [hazard ratio 0.66, confidence interval 0.46 to 0.96, P = 0.027]). In total, 54 cases of stroke occurred in 3439 patients (crude rate 1.6%) receiving dronedarone compared to 76 strokes in 3048 patients on placebo (crude rate 2.5%), respectively. Dronedarone can be used for maintenance of sinus rhythm and can reduce stroke in patients with AF who receive usual care, which includes antithrombotic therapy and heart rate control.

A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration

PubMed Central

Hashimoto, Koshi; Ota, Masaki; Irie, Tadanobu; Takata, Daisuke; Nakajima, Tadashi; Kaneko, Yoshiaki; Tanaka, Yuko; Matsumoto, Shunichi; Nakajima, Yasuyo; Kurabayashi, Masahiko; Oyama, Tetsunari; Takeyoshi, Izumi; Mori, Masatomo; Yamada, Masanobu

2015-01-01

Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT)) and destructive thyroiditis (type 2 AIT). We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone), the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration. PMID:25664188

[Inter-regional differences in dysthyroidism due to amiodarone: comparison of spontaneous notifications in Aquitaine, Midi-Pyrenees and Languedoc-Roussillon].

PubMed

Bagheri, H; Lapeyre-Mestre, M; Levy, C; Haramburu, F; Hillaire-Buys, D; Blayac, J P; Montastruc, J L

2001-01-01

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo.

PubMed

Grossman, M; Dobrev, D; Kirch, W

1998-09-01

Amiodarone, a class III antiarrhythmic agent, is a potent coronary vasodilator. However, direct evidence for its vasodilatory effects in human vasculature in vivo is not available. The aim of the study was to investigate the short-term effects of amiodarone in preconstricted human hand veins and to explore the underlying mechanisms. Thirty-one healthy male volunteers were studied with the use of the dorsal hand vein compliance technique. The hand veins of the subjects were preconstricted with the alpha 1-adrenergic receptor agonist phenylephrine, and amiodarone, inhibitors of nitric oxide formation (NG-monomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent potassium channels (glyburide [INN, glibenclamide]) were infused in the presence or absence of a cyclooxygenase inhibitor (acetylsalicylic acid), and the venodilator effect was measured. Furthermore, amiodarone was infused in prostaglandin F2 alpha (dinoprost)-preconstricted hand veins. Amiodarone produced dose-dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced venodilation was lower in dinoprost compared with phenylephrine-preconstricted veins. Pretreatment with acetylsalicylic acid reduced the amiodarone-induced venodilation by 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decreased the venodilatory response of amiodarone by 31% +/- 11%, whereas only a slight but not statistically significant additional reduction in venodilation was detected after pretreatment with acetylsalicylic acid. Infusion of the solvents of commercially available amiodarone (polysorbate 80 and benzyl alcohol) did not cause vasodilation in phenylephrine-preconstricted veins. Amiodarone dilates preconstricted human hand veins in vivo and acts as a venodilator through the cyclooxygenase pathway, activation of nitric oxide synthase, and blockade of alpha adrenergic mechanisms.

[Amiodarone and thyroid].

PubMed

Capraro, Joël; Thalmann, Sébastien

2011-06-01

Amiodarone is a widely used antiarrythmic drug and can lead either to hypothyroidism or hyperthyroidism due to its molecular structure which is similar to levothyroxin. Amiodarone induced hypothyroidism can be treated easely with hormonal subsitution. Hyperthyroidism is more challenging. There exist two forms of amiodarone-induced Hyperthyroidism (AIT): AIT type 1 is directly related to the iodine compound of amiodarone and responds to thyreostatic therapy. Type 2 is a consequence of the direct toxicity of amiodarone to the thyroid gland and is treated primarily with glucocorticoids. However, this differentiation often is impossible in clinical settings and a pragmatic approach is needed.

Severe acute hepatitis following intravenous amiodarone : a case report and review of the literature.

PubMed

Stratton, A; Fenderson, J; Kenny, P; Helman, D L

2015-06-01

Hepatotoxic complications of long-term oral amiodarone therapy have been well described ; however, liver injury secondary to parenteral infusion of amiodarone is uncommon, potentially fatal, and poorly understood. The hepatotoxicity is thought to result from the diluent polysorbate 80 and not the amiodarone its self. Theories suggest an allergic or immunologic response leading to alterations in the hepatocellular membrane while some propose that ischemia, not a drug reaction, is truly to blame. Both the PubMed and Embase databases were searched for cases of acute hepatitis implicating intravenous amiodarone with a total of 25 cases from 1986 to 2012 identified. Each case was then carefully evaluated to determine the connection between parenteral amiodarone and acute hepatotoxicity while assessing for evidence of potential ischemia. Of the 25 published cases of amiodarone induced acute hepatotoxicity available for review, only 10 provide evidence to conclusively implicate parenteral amiodarone as the etiology. We add the eleventh reported case of parenteral amiodarone induced acute severe hepatitis to the literature and report the most comprehensive review of this topic to date. There is sufficient evidence to support amiodarone induced acute hepatotoxicity as a unique entity separate from ischemic hepatitis. If suspected, parenteral amiodarone should be discontinued and held indefinitely. © Acta Gastro-Enterologica Belgica.

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality.

PubMed

Cooper, Lauren B; Mentz, Robert J; Edwards, Leah B; Wilk, Amber R; Rogers, Joseph G; Patel, Chetan B; Milano, Carmelo A; Hernandez, Adrian F; Stehlik, Josef; Lund, Lars H

2017-02-01

Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Analysis of computed tomography density of liver before and after amiodarone administration.

PubMed

Matsuda, Masazumi; Otaka, Aoi; Tozawa, Tomoki; Asano, Tomoyuki; Ishiyama, Koichi; Hashimoto, Manabu

2018-05-01

To evaluate CT density of liver changes between before and after amiodarone administration. Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration. Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration. CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats.

PubMed

Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

2012-01-01

Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats.

Amiodarone-Induced Thyroid Dysfunction: A Clinical Update.

PubMed

Elnaggar, Mohamed Nabil; Jbeili, Kahtan; Nik-Hussin, Nik; Kozhippally, Mohandas; Pappachan, Joseph M

2018-06-01

Amiodarone is one of the most commonly prescribed antiarrhythmic agents in clinical practice owing to its efficacy, even with high toxicity profile. The high iodine content and the prolonged biological half-life of the drug can result in thyroid dysfunction in a high proportion of patients treated with amiodarone even after cessation of amiodarone. Both hypothyroidism and hyperthyroidism are common side effects that mandate regular monitoring of patients with thyroid function tests. Amiodarone-induced hypothyroidism (AIH) is diagnosed and managed in the same way as a usual case of hypothyroidism. However, differential diagnosis and clinical management of amiodarone-induced thyrotoxicosis (AIT) subtypes can be challenging. With the aid of a case snippet, we update the current evidence for the diagnostic work up and management of patients with amiodarone-induced thyroid dysfunction in this article. © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy and safety of dronedarone: a review of randomized trials.

PubMed

Christiansen, Christine Benn; Torp-Pedersen, Christian; Køber, Lars

2010-01-01

Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated. This is a review of seven studies on dronedarone. DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL. Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.

Pseudocyanotic pigmentation of the skin induced by amiodarone: a light and electron microscopic study.

PubMed Central

Delage, C.; Lagacé, R.; Huard, J.

1975-01-01

An unusual bluish discolouration of the nose was noticed in a woman 9 months after she had begun treatment with a coronary vasodilator, amiodarone hydrochloride. Cutaneous biopsies of the nose were obtained 6 and 9 months later for light and electron microscopic studies. In the dermis were histiocytes containing cytoplasmic yellow-brown granules with histochemical properties of melanin and lipofuscin. Ultrastructurally the granules appeared as lysosomal membrane-bound dense bodies similar to lipofuscin. Similar granules were observed at diascopy in both corneas. The pathogenesis is obscure. A storage disease involving the drug or its metabolites cannot be ruled out. Another possibility is that amiodarone accelerates the normal cellular autophagocytosis, resulting in increased production of lipofuscin, which then accumulates in lysosomes because of a deficiency in lipolytic enzymes. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 8 PMID:47784

Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.

PubMed

Kudenchuk, Peter J; Brown, Siobhan P; Daya, Mohamud; Rea, Thomas; Nichol, Graham; Morrison, Laurie J; Leroux, Brian; Vaillancourt, Christian; Wittwer, Lynn; Callaway, Clifton W; Christenson, James; Egan, Debra; Ornato, Joseph P; Weisfeldt, Myron L; Stiell, Ian G; Idris, Ahamed H; Aufderheide, Tom P; Dunford, James V; Colella, M Riccardo; Vilke, Gary M; Brienza, Ashley M; Desvigne-Nickens, Patrice; Gray, Pamela C; Gray, Randal; Seals, Norman; Straight, Ron; Dorian, Paul

2016-05-05

Antiarrhythmic drugs are used commonly in out-of-hospital cardiac arrest for shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, but without proven survival benefit. In this randomized, double-blind trial, we compared parenteral amiodarone, lidocaine, and saline placebo, along with standard care, in adults who had nontraumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia after at least one shock, and vascular access. Paramedics enrolled patients at 10 North American sites. The primary outcome was survival to hospital discharge; the secondary outcome was favorable neurologic function at discharge. The per-protocol (primary analysis) population included all randomly assigned participants who met eligibility criteria and received any dose of a trial drug and whose initial cardiac-arrest rhythm of ventricular fibrillation or pulseless ventricular tachycardia was refractory to shock. In the per-protocol population, 3026 patients were randomly assigned to amiodarone (974), lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%, respectively, survived to hospital discharge. The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], -0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points (95% CI, -1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7 percentage points (95% CI, -3.2 to 4.7; P=0.70). Neurologic outcome at discharge was similar in the three groups. There was heterogeneity of treatment effect with respect to whether the arrest was witnessed (P=0.05); active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing than did recipients of lidocaine or placebo. Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT01401647.).

Hepatic cells derived from human skin progenitors show a typical phospholipidotic response upon exposure to amiodarone.

PubMed

Natale, Alessandra; Boeckmans, Joost; Desmae, Terry; De Boe, Veerle; De Kock, Joery; Vanhaecke, Tamara; Rogiers, Vera; Rodrigues, Robim M

2018-03-01

Phospholipidosis is a metabolic disorder characterized by intracellular accumulation of phospholipids. It can be caused by short-term or chronic exposure to cationic amphiphilic drugs (CADs). These compounds bind to phospholipids, leading to inhibition of their degradation and consequently to their accumulation in lysosomes. Drug-induced phospholipidosis (DIPL) is frequently at the basis of discontinuation of drug development and post-market drug withdrawal. Therefore, reliable human-relevant in vitro models must be developed to speed up the identification of compounds that are potential inducers of phospholipidosis. Here, hepatic cells derived from human skin (hSKP-HPC) were evaluated as an in vitro model for DIPL. These cells were exposed over time to amiodarone, a CAD known to induce phospholipidosis in humans. Transmission electron microscopy revealed the formation of the typical lamellar inclusions in the cell cytoplasm. Increase of phospholipids was already detected after 24 h exposure to amiodarone, whereas a significant increase of neutral lipid vesicles could be observed after 72 h. At the transcriptional level, the modulation of genes involved in DIPL was detected. These results provide a valuable indication of the applicability of hSKP-HPC for the quick assessment of drug-induced phospholipidosis in vitro, early in the drug development process. Copyright © 2017 Elsevier B.V. All rights reserved.

[Acute hepatitis following amiodarone administration].

PubMed

Tagliamonte, E; Cice, G; Ducceschi, V; Mayer, M S; Iacono, A

1997-09-01

A 61 year old man, treated with amiodarone since 1993 for resistant supraventricular arrhythmias, developed acute hepatitis after an intravenous amiodarone administration. Kidney and liver function tests were performed and pointed out abnormal results. Symptoms ascribable to hepatotoxicity were absent. These changes returned to normal levels within 20 days from withdrawal of the drug. Amiodarone hepatotoxicity can be related to prolonged therapy with a high dose. Intravenous amiodarone may cause acute hepatic disease, but it is suggested that polysorbate 80, a solvent added to the intravenous infusion, is a more likely cause of this complication.

Acute hepatitis after amiodarone infusion.

PubMed

Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

2015-10-16

Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.

Amiodarone induced myxedema coma: Two case reports and literature review.

PubMed

Hawatmeh, Amer; Thawabi, Mohammad; Abuarqoub, Ahmad; Shamoon, Fayez

2018-05-21

Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Two cases of bilateral amiodarone-associated optic neuropathy.

PubMed

Chassang, B; Bonnin, N; Moisset, X; Citron, B; Clavelou, P; Chiambaretta, F

2014-03-01

The widespread use of amiodarone is limited by its toxicity, notably to the optic nerve. We report two cases of bilateral optic nerve neuropathy due to amiodarone, and provide a detailed description of the disease. The first case was a 59-year-old man complaining from insidious monocular loss of vision within ten months of initiating amiodarone. Funduscopy and optical coherence tomography showed bilateral optic disc edema. The second case was a 72-year-old man presenting with a decrease in visual acuity in his left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein angiography showed bilateral papillitis. In both cases, the clinical presentation was not suggestive of ischemic neuropathy, because of the preservation of visual acuity and the insidious onset. In addition, both cardiovascular and inflammatory work-up were normal. An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. Differentiating between amiodarone-associated optic neuropathy and anterior ischemic optic neuropathy may be complicated by the cardiovascular background of such patients. The major criterion is the absence of a severe decrease in visual acuity; other criteria are the normality of cardiovascular and inflammatory work-up, and the improvement or the absence of worsening of symptoms after discontinuation of amiodarone. Amiodarone-associated neuropathy remains a diagnosis of exclusion, and requires amiodarone discontinuation, which can only be done with the approval of a cardiologist, and sometimes requires replacement therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

PM101: a cyclodextrin-based intravenous formulation of amiodarone devoid of adverse hemodynamic effects.

PubMed

Cushing, Daniel J; Kowey, Peter R; Cooper, Warren D; Massey, Bill W; Gralinski, Michael R; Lipicky, Raymond J

2009-04-01

Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.

Dronedarone: current evidence and future questions.

PubMed

Schafer, Jeremy A; Kjesbo, Nicole K; Gleason, Patrick P

2010-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.

Prehospital amiodarone may increase the incidence of acute respiratory distress syndrome among patients at risk.

PubMed

Karnatovskaia, Lioudmila V; Festic, Emir; Gajic, Ognjen; Carter, Rickey E; Lee, Augustine S

2012-10-01

Amiodarone has been implicated as a risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) when used in the hospital. This study aims to estimate whether prehospital amiodarone also increases the risk of ALI/ARDS. Adult patients admitted to 22 centers with at least 1 risk factor for developing ALI were recruited. In a secondary analysis of this cohort, the prehospital use of amiodarone was documented on admission, and the patients followed for the primary outcome of ALI and secondary outcomes of ARDS, the need for invasive ventilation, and mortality. Dose/duration of amiodarone therapy was not available. Propensity matching was performed to account for imbalances in being assigned to amiodarone. The adjusted risk for ALI/ARDS was then estimated from a conditional logistic regression model of this propensity-matched set. Forty of 5584 patients were on amiodarone at the time of hospitalization; of those, 6 developed ALI, with 5 progressing to ARDS. In comparison, 371 patients not on amiodarone developed ALI, with 224 having ARDS. After propensity score matching, the prehospital use of amiodarone was not statistically associated with an increased risk for all ALI (odds ratio [OR], 1.8; 95% confidence interval [CI], 0.7-5.0; P = .25), invasive ventilation (OR, 1.9; 95% CI, 1.0-3.6; P = .059), or in-hospital mortality (OR, 1.2; 95% CI, 0.5-2.9; P = .75); but its use appeared to significantly increase the risk for ARDS (OR 3.8; 95% CI, 1.1-13.1; P = .036). Prehospital use of amiodarone may independently increase the risk for ARDS in patients who have at least 1 predisposing condition for ALI. Copyright © 2012 Elsevier Inc. All rights reserved.

Dronedarone: an amiodarone analogue.

PubMed

Doggrell, Sheila A; Hancox, Jules C

2004-04-01

Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.

Efficacy of amiodarone and lidocaine for preventing ventricular fibrillation after aortic cross-clamp release in open heart surgery: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Yong; Gu, Qiang; Chen, Hong-Wu; Peng, Huai-Ming; Jia, Dong-Yu; Zhou, Yu; Xiang, Mei-Xiang

The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC. Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies. We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16). Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

Synergistic Effects of Amiodarone and Fluconazole on Candida tropicalis Resistant to Fluconazole

PubMed Central

da Silva, Cecília Rocha; de Andrade Neto, João Batista; Sidrim, José Júlio Costa; Ângelo, Maria Rozzelê Ferreira; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; Brilhante, Raimunda Sâmia Nogueira; Macedo, Danielle Silveira; de Moraes, Manoel Odorico; Lobo, Marina Duarte Pinto; Grangeiro, Thalles Barbosa

2013-01-01

There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of Candida tropicalis and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of C. tropicalis that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis. PMID:23357774

Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis.

PubMed

Zhu, Ling; Zainudin, Sueziani Binte; Kaushik, Manish; Khor, Li Yan; Chng, Chiaw Ling

2016-01-01

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases

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

Hawthorne, G.C.; Campbell, N.P.; Geddes, J.S.

1985-06-01

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. The authors conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop inmore » the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.« less

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.

Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation.

PubMed

Catherwood, E; Fitzpatrick, W D; Greenberg, M L; Holzberger, P T; Malenka, D J; Gerling, B R; Birkmeyer, J D

1999-04-20

Physicians managing patients with nonvalvular atrial fibrillation must consider the risks, benefits, and costs of treatments designed to restore and maintain sinus rhythm compared with those of rate control with antithrombotic prophylaxis. To compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin. A Markov decision-analytic model was designed to simulate long-term health and economic outcomes. Published literature and hospital accounting information. Hypothetical cohort of 70-year-old patients with different baseline risks for stroke. 3 months. Societal. Therapeutic strategies using different combinations of cardioversion alone, cardioversion plus amiodarone or quinidine therapy, and rate control with antithrombotic treatment. Expected costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. Strategies involving cardioversion alone were more effective and less costly than those not involving this option. For patients at high risk for ischemic stroke (5.3% per year), cardioversion alone followed by repeated cardioversion plus amiodarone therapy on relapse was most cost-effective ($9300 per QALY) compared with cardioversion alone followed by warfarin therapy on relapse. This strategy was also preferred for the moderate-risk cohort (3.6% per year), but the benefit was more expensive ($18,900 per QALY). In the lowest-risk cohort (1.6% per year), cardioversion alone followed by aspirin therapy on relapse was optimal. The choice of optimal strategy and incremental cost-effectiveness was substantially influenced by the baseline risk for stroke, rate of stroke in sinus rhythm, efficacy of warfarin, and costs and utilities for long-term warfarin and amiodarone therapy. Cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation. On relapse of arrhythmia, repeated cardioversion plus low-dose amiodarone is cost-effective for patients at moderate to high risk for ischemic stroke.

Sternal Route More Effective than Tibial Route for Intraosseous Amiodarone Administration in a Swine Model of Ventricular Fibrillation.

PubMed

Burgert, James M; Martinez, Andre; O'Sullivan, Mara; Blouin, Dawn; Long, Audrey; Johnson, Arthur D

2018-01-01

The pharmacokinetics of IO administered lipid soluble amiodarone during ventricular fibrillation (VF) with ongoing CPR are unknown. This study measured mean plasma concentration over 5 minutes, maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) of amiodarone administered by the sternal IO (SIO), tibial IO (TIO), and IV routes in a swine model of VF with ongoing CPR. Twenty-one Yorkshire-cross swine were randomly assigned to three groups: SIO, TIO, and IV. Ventricular fibrillation was induced under general anesthesia. After 4 minutes in VF, 300 mg amiodarone was administered as indicated by group assignment. Serial blood specimens collected at 30, 60, 90, 120, 150, 180, 240, and 300 seconds were analyzed using high performance liquid chromatography with tandem mass spectrometry. The mean plasma concentration of IV amiodarone over 5 minutes was significantly higher than the TIO group at 60 seconds (P = 0.02) and 90 seconds (P = 0.017) post-injection. No significant differences in Cmax between the groups were found (P <0.05). The Tmax of amiodarone was significantly shorter in the SIO (99 secs) and IV (86 secs) groups compared to the TIO group (215 secs); P = 0.002 and P = 0.002, respectively. The SIO and IV routes of amiodarone administration were comparable. The TIO group took nearly three times longer to reach Tmax than the SIO and IV groups, likely indicating depot of lipid-soluble amiodarone in adipose-rich tibial yellow bone marrow. The SIO route was more effective than the TIO route for amiodarone delivery in a swine model of VF with ongoing CPR. Further investigations are necessary to determine if the kinetic differences found between the SIO and TIO routes in this study affect survival of VF in humans.

PM101: intravenous amiodarone formulation changes can improve medication safety.

PubMed

Souney, Paul F; Cooper, Warren D; Cushing, Daniel J

2010-03-01

Intravenous amiodarone (A-IV) is used to manage ventricular and atrial arrhythmias. The current formulation uses polysorbate 80 and benzyl alcohol to maintain amiodarone in solution, and these co-solvents are linked with clinically-important adverse events and pharmaceutical incompatibilities. PM101 is a recently FDA-approved intravenous formulation of amiodarone that uses a cyclodextrin to solubilize amiodarone. This review describes the clinical and pharmaceutical development of formulations of amiodarone for intravenous administration. The medical and pharmaceutical literature was searched for papers discussing A-IV, PM101 and their formulation components. Relevant literature was identified starting from 1948 to the present. The reader will learn about the important medical and pharmaceutical issues complicating A-IV administration, including an understanding of related hypotension and compatibility with commonly used infusion materials and how these issues may impact drug safety. PM101 has been developed to address several of these important issues. PM101 is a new formulation of A-IV that is stable in commonly used infusion materials and avoids co-solvent related toxicities.

Amiodarone-Associated Optic Neuropathy: A Critical Review

PubMed Central

Passman, Rod S.; Bennett, Charles L.; Purpura, Joseph M.; Kapur, Rashmi; Johnson, Lenworth N.; Raisch, Dennis W.; West, Dennis P.; Edwards, Beatrice J.; Belknap, Steven M.; Liebling, Dustin B.; Fisher, Mathew J.; Samaras, Athena T.; Jones, Lisa-Gaye A.; Tulas, Katrina-Marie E.; McKoy, June M.

2011-01-01

Although amiodarone is the most commonly prescribed antiarrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System (FDA-AERS) and published case reports were reviewed. A total of 296 reports were identified: 214 from AERS, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone associated optic neuropathy (44%) was the most common presentation, and nearly one-third were asymptomatic. Optic disc edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (< 20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. PMID:22385784

Amiodarone causes acute oxidant lung injury in ventilated and perfused rabbit lungs.

PubMed

Kennedy, T P; Gordon, G B; Paky, A; McShane, A; Adkinson, N F; Peters, S P; Friday, K; Jackman, W; Sciuto, A M; Gurtner, G H

1988-07-01

Amiodarone (ADR), a new antiarrhythmic drug for life-threatening cardiac arrhythmias, causes pneumonitis or lung fibrosis in a sizeable minority of patients. The cause of lung damage is not known. We have shown that infusion of 10 mg amiodarone into the inflow circuit of ventilated and perfused rabbit lungs causes immediate increase in pulmonary artery pressure (mean +/- SEM) (from 13.6 +/- 1.2 to 40.6 +/- 9.5 mm Hg, p less than 0.01) and pulmonary edema with marked increase in the pulmonary generation of thromboxane and leukotrienes C4 and/or D4. Albumin (2 g%) in the perfusate prevents any increase in lung perfusion pressure or edema formation. When lung perfusion pressure increase is blocked with the combined cyclooxygenase and lipoxygenase inhibitor enolicam sodium (CG5391B, 35 microM in perfusate), significant lung edema still occurs after amiodarone, indicating that amiodarone causes increased alveolar-capillary membrane permeability. Addition of catalase (100 U/ml) or superoxide dismutase and catalase (100 U/ml each) to perfusate fails to protect from amiodarone lung injury. Immediate infusion of amiodarone (10 mg) into lungs ventilated with room air (ADR + RA) causes an increase in lung weight gain from baseline (delta W) of 5.7 +/- 1.5 g/min. Compared with ADR + RA, ventilation of lungs with 4% O2 (delta W = 0.7 +/- 0.3 g/min, p less than 0.05), pretreatment of rabbits for 3 days with butylated hydroxyanisole (BHA, 100 mg/kg/day i.p., delta W = 0.05 +/- 0.02 g/min, p less than 0.01), pretreatment of rabbits for 3 days with vitamin E (Vit E, 300 U/day orally, delta W = 0.6 +/- 0.2 g/min, p less than 0.05), or addition of N-acetylcysteine to the lung perfusate (NAC, 5 mM, delta W = 0.1 +/- 0.08 g/min, p less than 0.01) all protect from lung edema formation after amiodarone. Amiodarone (100 mg) also caused a marked increase in luminol-enhanced lung chemiluminescence, lung production of superoxide anion (O2-), and tissue levels of lung glutathione disulfide. These results suggest that amiodarone causes lung injury by an oxidant mechanism.

Sex Differences in the Relationship Between Amiodarone Use and the Need for Permanent Pacing in Patients With Atrial Fibrillation

PubMed Central

Essebag, Vidal; Reynolds, Matthew R.; Hadjis, Tom; Lemery, Robert; Olshansky, Brian; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter

2008-01-01

Background Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation (AF) and prior myocardial infarction. The aims of this study were to determine prospectively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex. Methods The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs, Therapies, Adverse events, and Lifestyle (FRACTAL). Multivariable Cox regression models, including time-dependent covariates accounting for medication exposure, were used to evaluate the risk of pacemaker insertion associated with amiodarone use. Results Amiodarone use was associated with an increased risk of pacemaker insertion (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.08–3.76) after adjustment for age, sex, atrial flutter, coronary artery disease, heart failure, and hypertension. The effect of amiodarone use was modified by sex, with a significant risk in women but not in men (HR, 4.69; 95% CI, 1.99–11.05 vs HR, 1.05; 95% CI, 0.42–2.58 [P = .02]). This interaction remained significant after adjustment for weight, body mass index, weight-adjusted amiodarone dose, and use of other antiarrhythmic or rate control drugs. Conclusion The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men, independent of weight or body mass index. PMID:17698688

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

PubMed

Kudenchuk, Peter J; Leroux, Brian G; Daya, Mohamud; Rea, Thomas; Vaillancourt, Christian; Morrison, Laurie J; Callaway, Clifton W; Christenson, James; Ornato, Joseph P; Dunford, James V; Wittwer, Lynn; Weisfeldt, Myron L; Aufderheide, Tom P; Vilke, Gary M; Idris, Ahamed H; Stiell, Ian G; Colella, M Riccardo; Kayea, Tami; Egan, Debra; Desvigne-Nickens, Patrice; Gray, Pamela; Gray, Randal; Straight, Ron; Dorian, Paul

2017-11-28

Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo ( P <0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge ( P =0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P =0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P =0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647. © 2017 American Heart Association, Inc.

Herb-drug pharmacokinetic interaction between carica papaya extract and amiodarone in rats.

PubMed

Rodrigues, Márcio; Alves, Gilberto; Francisco, Joana; Fortuna, Ana; Falcão, Amílcar

2014-01-01

Carica papaya has been traditionally used worldwide in folk medicine to treat a wide range of ailments in humans, including the management of obesity and digestive disorders. However, scientific information about its potential to interact with conventional drugs is lacking. Thus, this work aimed to investigate the interference of a standardized C. papaya extract (GMP certificate) on the systemic exposure to amiodarone (a narrow therapeutic index drug) in rats. In the first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. papaya (1230 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in the second study, rats were pre-treated for 14 days with C. papaya (1230 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the herbal extract vehicle. Blood samples were collected before dosing and at 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h following amiodarone administration; in addition, at 24 h post-dose, blood and tissues (heart, liver, kidneys and lungs) were also harvested. Thereafter, the concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were determined in plasma and tissue samples employing a high-performance liquid chromatography-diode array detection method previously developed and validated. In both studies was observed a delay in attaining the maximum plasma concentrations of amiodarone (tmax) in the rats treated with the extract. Nevertheless, it must be highlighted the marked increase (60-70%) of the extent of amiodarone systemic exposure (as assessed by AUC0-t and AUC0-∞) in the rats pre-treated with C. papaya comparatively with the control (vehicle) group. The results herein found suggest an herb-drug interaction between C. papaya extract and amiodarone, which clearly increase the drug bioavailability. To reliably assess the clinical impact of these findings appropriate human studies should be conducted.

Effect of intravenous amiodarone on QT and T peak-T end dispersions in patients with nonischemic heart failure treated with cardiac resynchronization-defibrillator therapy and electrical storm.

PubMed

Ogiso, Masataka; Suzuki, Atsushi; Shiga, Tsuyoshi; Nakai, Kenji; Shoda, Morio; Hagiwara, Nobuhisa

2015-02-01

The effect of intravenous amiodarone on spatial and transmural dispersion of ventricular repolarization in patients receiving cardiac resynchronization therapy (CRT) remains unclear. We studied 14 patients with nonischemic heart failure who received CRT with a defibrillator, experienced electrical storm and were treated with intravenous amiodarone. Each patient underwent 12-lead electrocardiography (ECG) and 187-channel repolarization interval-difference mapping electrocardiography (187-ch RIDM-ECG) before and during the intravenous administration of amiodarone infusion. A recurrence of ventricular tachyarrhythmia was observed in 2 patients during the early period of intravenous amiodarone therapy. Intravenous amiodarone increased the corrected QT interval (from 470±52 ms to 508±55 ms, P=0.003), but it significantly decreased the QT dispersion (from 107±35 ms to 49±27 ms, P=0.001), T peak-T end (Tp-e) dispersion (from 86±17 ms to 28±28 ms, P=0.001), and maximum inter-lead difference between corrected Tp-e intervals as measured by using the 187-ch RIDM-ECG (from 83±13 ms to 50±19 ms, P=0.001). Intravenous amiodarone suppressed the electrical storm and decreased the QT and Tp-e dispersions in patients treated by using CRT with a defibrillator.

Amiodarone induced pneumonitis and hyperthyroidism: case report.

PubMed

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

2008-09-01

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

Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets.

PubMed

Weir, S J; Myers, V A; Bengtson, K D; Ueda, C T

1985-12-01

The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

PubMed

Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

2007-12-01

Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of <2 mg/mL amiodarone were established to reduce the risk of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

Oral amiodarone: historical overview and development.

PubMed

Pollak, P T

1998-01-01

To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic properties. Review of relevant literature. In the 1970s and 1980s a plethora of new antiarrhythmic agents, including amiodarone, was introduced. Amiodarone is predominately a class III antiarrhythmic, but also possesses class I, II, and IV effects. By 1977 it was described as the ideal antiarrhythmic agent. However, clinicians underestimated potential difficulties caused by misunderstanding its variable absorption, slow initial response at nonloading dosages, and extended half-life. Elevated dosages also produced frequent adverse effects. Thus, early enthusiasm for the drug's efficacy was gradually replaced by a focus on its toxicity. The 1990s witnessed reacceptance of the agent as more logical initial regimens and lower maintenance dosages decreased adverse effects, and amiodarone emerged as one of the few drugs effective in suppressing and preventing arrhythmias that does not increase mortality. Remaining challenges include delineation of an optimal oral regimen, identification of markers useful in clinical monitoring, and elucidation of the relationship between dose-tissue concentration and response and dose-toxicity associations. Amiodarone is an increasingly valuable component of today's antiarrhythmic therapy.

Evaluation of 99mTc-MIBI in thyroid gland imaging for the diagnosis of amiodarone-induced thyrotoxicosis

PubMed Central

Zhang, Ruiguo

2017-01-01

Objective: Amiodarone-induced thyrotoxicosis (AIT) is caused by amiodarone as a side effect of cardiovascular disease treatment. Based on the differences in their pathological and physiological mechanisms, many methods have been developed so far to differentiate AIT subtypes such as colour flow Doppler sonography (CFDS) and 24-h radioiodine uptake (RAIU). However, these methods suffer from inadequate accuracy in distinguishing different types of AITs and sometimes lead to misdiagnosis and delayed treatments. Therefore, there is an unmet demand for an efficient method for accurate classification of AIT. Methods: Technetium-99 methoxyisobutylisonitrile (99mTc-MIBI) thyroid imaging was performed on 15 patients for AIT classification, and the results were compared with other conventional methods such as CFDS, RAIU and 99mTcO4 imaging. Results: High uptake and retention of MIBI in thyroid tissue is characteristic in Type I AIT, while in sharp contrast, low uptake of MIBI in the thyroid tissue was observed in Type II AIT. Mixed-type AIT shows uptake value between Types I and II. MIBI imaging outperforms other methods with a lower misdiagnosis rate. Conclusion: Among the methods evaluated, MIBI imaging enables an accurate identification of Type I, II and mixed-type AITs by showing distinct images for different types of AITs. The results obtained from our selected subjects revealed that MIBI imaging is a reliable method for diagnosis and classification of AITs and MIBI imaging has potential in the treatment of thyroid diseases. Advances in knowledge: 99mTc-MIBI imaging is a useful method for the diagnosis of AIT. It can distinguish different types of AITs especially for mixed-type AIT, which is usually difficult to treat. 99mTc-MIBI has potential advantages over conventional methods in the efficient treatment of AIT. PMID:28106465

Is the Preoperative Administration of Amiodarone or Metoprolol More Effective in Reducing Atrial Fibrillation: After Coronary Bypass Surgery?

PubMed

Onk, Oruc Alper; Erkut, Bilgehan

2015-10-01

This study examined the influence of preoperative administration of amiodarone and metoprolol in preventing postoperative atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery.The study comprised 251 patients who underwent CABG surgery at our hospital between January 2012 and May 2014. The patients were randomly divided into 2 groups: amiodarone therapy group (n = 122 patients) and metoprolol therapy group (n = 129 patients).In the amiodarone group, the patients received amiodarone tablet orally 1 week before coronary bypass surgery and during the postoperative period. In the metoprolol group, the patients received metoprolol tablet orally 1 week before surgery and during the postoperative period. The AF development rate was retrospectively evaluated between the first 3 days and 4 weeks after surgery.AF developed in 14 patients in the amiodarone group and 16 patients in the metoprolol group 4 weeks after the operation (P = 0.612).No significant difference was observed between the groups in terms of intensive care unit and hospital stay. Furthermore, hospital charges were similar in both groups (P = 0.741).The results of the logistic regression analysis showed age, left ventricular ejection fraction, left atrial diameter, and aortic cross-clamping time to be predictors for postoperative AF.This study demonstrates that amiodarone and metoprolol have similar effects in prevention of AF after cardiac surgery. However, larger-scale studies need to be conducted to substantiate these findings.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Bradycardiac Effects Caused by Co-Administration of Sofosbuvir and Amiodarone.

PubMed

Yu, Yankun; Liu, Feng; He, Liuming; Ramakrishna, Seeram; Zheng, Monica; Bu, Lei; Xu, Ying

2018-05-30

Co-administration of sofosbuvir, an anti-hepatitis C virus medication, and antiarrhythmic amiodarone causes symptomatic severe bradycardia in patients and animal models. However, in a few in vitro studies, the combination of sofosbuvir and amiodarone resulted in tachycardiac effects in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This discrepancy may be attributable to the use of immature hiPSC-CMs in the in vitro studies. To address this, we evaluated the ability of our in-house hiPSC-CMs to assess the interactions between sofosbuvir and amiodarone in vitro. We performed whole-cell patch recordings on hiPSC-CMs to examine the cardiac effect of sofosbuvir and amiodarone, alone or in combination. We found that sofosbuvir and amiodarone caused bradycardiac effects (the beating rate decreased to 75% of the vehicle control, P < 0.001) on our hiPSC-CMs when applied in combination, but they had no significant effect when applied alone. Furthermore, the bradycardiac effect was membrane potential dependent: it increased with depolarization. This raised the possibility that the bradycardiac effects in vivo may originate in nodal cells, which have a more depolarized resting membrane potential compared with ventricular cells. The bradycardiac effects of sofosbuvir plus amiodarone in vitro are consistent with the clinical phenotype and suggest that our hiPSC-CMs may serve as a useful tool in assessing cardiac safety during drug discovery and development process.

The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type.

PubMed

Tomisti, Luca; Rossi, Giuseppe; Bartalena, Luigi; Martino, Enio; Bogazzi, Fausto

2014-09-01

Considering the different pathogenic mechanisms of the two main forms of amiodarone-induced thyrotoxicosis (AIT), we ascertained whether this results in a different onset time as well. We retrospectively analyzed the clinical records of 200 consecutive AIT patients (157 men and 43 women; mean age 62.2±12.6 years) referred to our Department from 1987 to 2012. The onset time of AIT was defined as the time elapsed from the beginning of amiodarone therapy and the first diagnosis of thyrotoxicosis, expressed in months. Factors associated with the onset time of AIT were evaluated by univariate and multivariate analyses. The median onset time of thyrotoxicosis was 3.5 months (95% CI 2-6 months) in patients with type 1 AIT (AIT1) and 30 months (95% CI 27-32 months, P<0.001) in those with type 2 AIT (AIT2). Of the total number of patients, 5% with AIT1 and 23% with AIT2 (P=0.007) developed thyrotoxicosis after amiodarone withdrawal. Factors affecting the onset time of thyrotoxicosis were the type of AIT and thyroid volume (TV). The different pathogenic mechanisms of the two forms of AIT account for different onset times of thyrotoxicosis in the two groups. Patients with preexisting thyroid abnormalities (candidate to develop AIT1) may require a stricter follow-up during amiodarone therapy than those usually recommended. In AIT1, the onset of thyrotoxicosis after amiodarone withdrawal is rare, while AIT2 patients may require periodic tests for thyroid function longer after withdrawing amiodarone. © 2014 European Society of Endocrinology.

Iodine-induced hyperthyroidism as combination of different etiologies: an overlooked entity in the elderly.

PubMed

Foppiani, Luca; Cascio, Christian; Lo Pinto, Giuliano

2016-10-01

Iodine-induced thyrotoxicosis, which raises several diagnostic and therapeutical challenges, is often overlooked. Hyperthyroidism can induce atrial fibrillation, a harmful arrhythmia which can precipitate heart failure and cause stroke. We report the case of an elderly man who was diagnosed with tachyfibrillation secondary to hyperthyroidism. Thyroid hyperfunction was subsequently related both to previous amiodarone therapy (probably mixed form) and the recent use of iodinated contrast medium for computed tomography scan. Thyroid ultrasonography showed a plongeant multinodular goitre. After initial worsening, thyroid function improved slowly but progressively on high-dose thyreostatic therapy combined with steroid therapy; tachyfibrillation caused heart failure and a thrombus in the left atrium, and proved initially resistant to combined antiarrhythmic treatments. Progressive reduction in thyroid hormone levels, together with combined cardiologic therapies, controlled the heart rate, though atrial fibrillation persisted; anticoagulant therapy resolved the atrial thrombus. Alterations in thyroid function are common in amiodarone-treated patients, who therefore require regular hormonal checks. The different forms of amiodarone-induced thyrotoxicosis must be investigated, since they require different therapies, though mixed forms often occur. The superimposition of further iodine excess due to other causes may be catastrophic and cause severe cardiac problems in these patients.

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

PubMed

Slavik, R S; Tisdale, J E; Borzak, S

2001-01-01

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed. Copyright 2001 by W.B. Saunders Company

Management of atrial fibrillation: focus on the role of dronedarone.

PubMed

Cheng, Judy Wm

2011-01-01

Dronedarone is an amiodarone derivative that was approved in the US in July 2009 to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF), who are in sinus rhythm (SR), or who will be cardioverted. This article reviews the pharmacology, adverse effects, and clinical evidence available to date on the use of dronedarone in the management of AF and its potential role in the emergency department setting. In the EURIDIS and ADONIS studies evaluating the efficacy of dronedarone in maintaining SR, dronedarone significantly reduced the risk of recurrence of AF compared to placebo, by 22% and 27%, respectively. The ERATO study examined the ability of dronedarone to control ventricular rate in permanent AF. The DIONYSOS study demonstrated that recurrences of AF were more frequent with dronedarone. However, discontinuation of therapy due to intolerance was more frequent with amiodarone. Furthermore, the ATHENA study demonstrated that dronedarone reduced mortality and cardiovascular hospitalization by 24% (P < 0.05) in patients in SR but with other associated risks and a history of AF. However, the ANDROMEDA study, evaluating the use of dronedarone in patients with recent decompensated heart failure, and the PALLAS study, evaluating the use of dronedarone in patients with chronic AF, were both terminated prematurely due to a trend toward an increased risk of cardiovascular events. Dronedarone has been demonstrated to be effective in reducing the incidence of AF recurrence. It appears to be less effective but better tolerated than amiodarone. Dronedarone appears to have a low proarrhythmic risk and is the first anti-arrhythmic that has been demonstrated to reduce cardiovascular mortality and cardiovascular hospitalization in clinically stable patients with other risk factors for recurrent AF. Therefore, dronedarone can be recommended as an anti-arrhythmic of choice in clinically stable patients for maintaining SR. If dronedarone is to be used in a patient with chronic stable heart failure, the patient must be monitored closely for any worsening of heart failure symptoms. The drug must be discontinued should the heart failure symptoms worsen.

The effects of sesame oil on the prevention of amiodarone-induced phlebitis.

PubMed

Bagheri-Nesami, Masoumeh; Shorofi, Seyed Afshin; Hashemi-Karoie, Seyedeh Zahra; Khalilian, Alireza

2015-01-01

Phlebitis is the most common complication associated with peripheral intravenous infusion of amiodarone. The purpose of this study is to determine the effects of sesame oil on the prevention of amiodarone-induced phlebitis. This is a double-blind randomized controlled trial. Thirty-six patients hospitalized in a coronary care unit were randomly allocated into two groups using a convenience sampling method. Following peripheral intravenous cannulation, five drops of pure sesame oil were applied to the skin within a 10 cm radius of the infusion site prior to the administration of amiodarone in the intervention group. Sesame oil was rubbed on the skin at the infusion site every 6 h in the 24-h period of amiodarone infusion. In the control group, liquid paraffin, used as a placebo, was rubbed on the skin at the infusion site of amiodarone. Both groups were monitored for the development of phlebitis and its degree within the 24-h period of amiodarone infusion as well as 6 h after its administration. The incidence of phlebitis was confirmed and recorded by an assessor who was blind to the two groups. Data were analyzed using Statistical Package for Social Science (SPSS) version 18, and descriptive and inferential statistics such as Chi-square test, Kaplan-Meier, Hazard ratio, independent t-test, and Fisher's exact test. There was a statistically significant difference between the two groups in their catheter survival after 30 h and 10 min (P < 0.001). Over 60% of the patients (61.1%) in the intervention group did not show any sign of phlebitis, while 16.7% and 22.2% of the patients manifested signs of grade 2 and 3 phlebitis, respectively. In the control group, 22.2% of the patients showed no signs of phlebitis, while 5.6%, 27.8%, and 44.4% of the patients exhibited signs of grade 2, 3, and 4 phlebitis, respectively. The statistical analysis showed significant differences in the degree of phlebitis (P = 0.006) and the onset of phlebitis development (P < 0.001) between the two groups. It is recommended to apply sesame oil topically to the infusion site of amiodarone so as to reduce the rate of the development of amiodarone-related phlebitis.

The effects of sesame oil on the prevention of amiodarone-induced phlebitis

PubMed Central

Bagheri-Nesami, Masoumeh; Shorofi, Seyed Afshin; Hashemi-Karoie, Seyedeh Zahra; Khalilian, Alireza

2015-01-01

Background: Phlebitis is the most common complication associated with peripheral intravenous infusion of amiodarone. The purpose of this study is to determine the effects of sesame oil on the prevention of amiodarone-induced phlebitis. Materials and Methods: This is a double-blind randomized controlled trial. Thirty-six patients hospitalized in a coronary care unit were randomly allocated into two groups using a convenience sampling method. Following peripheral intravenous cannulation, five drops of pure sesame oil were applied to the skin within a 10 cm radius of the infusion site prior to the administration of amiodarone in the intervention group. Sesame oil was rubbed on the skin at the infusion site every 6 h in the 24-h period of amiodarone infusion. In the control group, liquid paraffin, used as a placebo, was rubbed on the skin at the infusion site of amiodarone. Both groups were monitored for the development of phlebitis and its degree within the 24-h period of amiodarone infusion as well as 6 h after its administration. The incidence of phlebitis was confirmed and recorded by an assessor who was blind to the two groups. Data were analyzed using Statistical Package for Social Science (SPSS) version 18, and descriptive and inferential statistics such as Chi-square test, Kaplan–Meier, Hazard ratio, independent t-test, and Fisher's exact test. Results: There was a statistically significant difference between the two groups in their catheter survival after 30 h and 10 min (P < 0.001). Over 60% of the patients (61.1%) in the intervention group did not show any sign of phlebitis, while 16.7% and 22.2% of the patients manifested signs of grade 2 and 3 phlebitis, respectively. In the control group, 22.2% of the patients showed no signs of phlebitis, while 5.6%, 27.8%, and 44.4% of the patients exhibited signs of grade 2, 3, and 4 phlebitis, respectively. The statistical analysis showed significant differences in the degree of phlebitis (P = 0.006) and the onset of phlebitis development (P < 0.001) between the two groups. Conclusions: It is recommended to apply sesame oil topically to the infusion site of amiodarone so as to reduce the rate of the development of amiodarone-related phlebitis. PMID:26120338

Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats.

PubMed

Rodrigues, Márcio; Alves, Gilberto; Falcão, Amílcar

2013-10-01

Citrus aurantium extract has been largely used in weight loss and sports performance dietary supplements. However, the safety of C. aurantium-containing products has been questioned mainly due to the association of its use with adverse events in the cardiovascular system. Therefore, this work aimed to assess the potential for herb-drug interactions among a standardized C. aurantium extract (GMP certificate) and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. aurantium (164 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in a second study, rats were pre-treated during 14 days with C. aurantium (164 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Overall, after analysis of the pharmacokinetic data, it deserves to be highlighted the significant increase of the peak plasma concentration of amiodarone in rats pre-treated with C. aurantium extract, while the extent of systemic exposure was comparable between both groups. This paper reports, for the first time, data on the potential of herb-drug interaction between C. aurantium extract and amiodarone. However, specific clinical trials should be performed to confirm these results in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Selective Late Sodium Current Inhibitor Eleclazine, Unlike Amiodarone, Does Not Alter Defibrillation Threshold or Dominant Frequency of Ventricular Fibrillation.

PubMed

Silva, Ana F G; Bonatti, Rodolfo; Batatinha, Julio A P; Nearing, Bruce D; Zeng, Dewan; Belardinelli, Luiz; Verrier, Richard L

2017-03-01

We examined the effects of the selective late INa inhibitor eleclazine on the 50% probability of successful defibrillation (DFT50) before and after administration of amiodarone to determine its suitability for use in patients with implantable cardioverter defibrillators (ICDs). In 20 anesthetized pigs, transvenous active-fixation cardiac defibrillation leads were fluoroscopically positioned into right ventricular apex through jugular vein. ICDs were implanted subcutaneously. Dominant frequency of ventricular fibrillation was analyzed by fast Fourier transform. The measurements were made before drug administration (control), and at 40 minutes after vehicle, eleclazine (2 mg/kg, i.v., bolus over 15 minutes), or subsequent/single amiodarone administration (10 mg/kg, i.v., bolus over 10 minutes). Eleclazine did not alter DFT50, dominant frequency, heart rate, or mean arterial pressure (MAP). Subsequent amiodarone increased DFT50 (P = 0.006), decreased dominant frequency (P = 0.022), and reduced heart rate (P = 0.031) with no change in MAP. Amiodarone alone increased DFT50 (P = 0.005; NS compared to following eleclazine) and decreased dominant frequency (P = 0.003; NS compared to following eleclazine). Selective late INa inhibition with eleclazine does not alter DFT50 or dominant frequency of ventricular fibrillation when administered alone or in combination with amiodarone. Accordingly, eleclazine would not be anticipated to affect the margin of defibrillation safety in patients with ICDs.

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

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

Wiersinga, W.M.; Touber, J.L.; Trip, M.D.

1986-08-01

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. /sup 99m/Tc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and dischargemore » of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I (5.4 +/- 0.8% (+/- SE) at 60 min) was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by /sup 99m/Tc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients.« less

Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial.

PubMed

Kudenchuk, Peter J; Brown, Siobhan P; Daya, Mohamud; Morrison, Laurie J; Grunau, Brian E; Rea, Tom; Aufderheide, Tom; Powell, Judy; Leroux, Brian; Vaillancourt, Christian; Larsen, Jonathan; Wittwer, Lynn; Colella, M Riccardo; Stephens, Shannon W; Gamber, Mark; Egan, Debra; Dorian, Paul

2014-05-01

Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT). ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after ≥1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score ≤3. The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating. Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice. Copyright © 2014 Mosby, Inc. All rights reserved.

Vitamin B6

MedlinePlus

... Cordarone)Amiodarone (Cordarone) might increase your sensitivity to sunlight. Taking vitamin B6 along with amiodarone (Cordarone) might ... or rashes on areas of skin exposed to sunlight. Be sure to wear sunblock and protective clothing ...

Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study.

PubMed

Kowey, Peter R; Crijns, Harry J G M; Aliot, Etienne M; Capucci, Alessandro; Kulakowski, Piotr; Radzik, David; Roy, Denis; Connolly, Stuart J; Hohnloser, Stefan H

2011-12-13

Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. Celivarone was not effective for the prevention of ICD interventions or sudden death. http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

Assessment of amiodarone-induced phospholipidosis in chimeric mice with a humanized liver.

PubMed

Sanoh, Seigo; Yamachika, Yuto; Tamura, Yuka; Kotake, Yaichiro; Yoshizane, Yasumi; Ishida, Yuji; Tateno, Chise; Ohta, Shigeru

2017-01-01

It is important to consider susceptibility to drug-induced toxicity between animals and humans. Chimeric mice with a humanized liver are expected to predict hepatotoxicity in humans. Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. In this study, we examined whether chimeric mice can reveal species differences in DIPL. Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis. Liquid chromatography-tandem mass spectrometry revealed that levels of PhCs tended to increase in the liver after administration of amiodarone. The liver of chimeric mice consists of human hepatocytes and residual mouse hepatocytes. We used imaging mass spectrometry (IMS) to evaluate the increase of PhCs in human and mouse hepatocytes after administration of amiodarone. IMS visualizes localization of endogenous and exogenous molecules in tissues. The IMS analysis suggested that the localized levels of several PhCs tended to be higher in the human hepatocytes than those in mouse hepatocytes, and PhC levels changed in response to amiodarone. Chimeric mice with a humanized liver will be useful to evaluate species differences in DIPL between mice and humans.

Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

PubMed

Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

2007-11-01

Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

Medication Review and Transitions of Care: A Case Report of a Decade-Old Medication Error.

PubMed

Comer, Rachel; Lizer, Mitsi

2017-10-01

A 69-year-old Caucasian male with a 25-year history of paranoid schizophrenia was brought to the emergency department because of violence toward the staff in his nursing facility. He was diagnosed with a urinary tract infection and was admitted to the behavioral health unit for medication stabilization. History included a five-year state psychiatric hospital admission and nursing facility placement. Because of poor cognitive function, the patient was unable to corroborate medication history, so the pharmacy student on rotation performed an in-depth chart review. The review revealed a transcription error in 2003 deleting amantadine 100 mg twice daily and adding amiodarone 100 mg twice daily. Subsequent hospitalization resulted in another transcription error increasing the amiodarone to 200 mg twice daily. All electrocardiograms conducted were negative for atrial fibrillation. Once detected, the consulted cardiologist discontinued the amiodarone, and the primary care provider was notified via letter and discharge papers. An admission four months later revealed that the nursing facility restarted the amiodarone. Amiodarone was discontinued and the facility was again notified. This case reviews how a 10-year-old medication error went undetected in the electronic medical records through numerous medication reconciliations, but was uncovered when a single comprehensive medication review was conducted.

Amiodarone-induced thyrotoxicosis: A review

PubMed Central

Tsang, Wendy; Houlden, Robyn L

2009-01-01

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) develops in 3% of amiodarone-treated patients in North America. AIT is classified as type 1 or type 2. Type 1 AIT occurs in patients with underlying thyroid pathology such as autonomous nodular goiter or Graves’ disease. Type 2 AIT is a result of amiodarone causing a subacute thyroiditis with release of preformed thyroid hormones into the circulation. OBJECTIVES: To review the literature and present an overview of the differentiation between and management of type 1 and type 2 AIT. METHODS: PubMed, the Cumulative Index to Nursing and Allied Health Literature and Medscape searches of all available English language articles from 1983 to 2006 were performed. Search terms included ‘amiodarone-induced thyrotoxicosis’, ‘complications’, ‘management’, ‘treatment’ and ‘colour flow Dopper sonography’. RESULTS: There is evidence to suggest that to differentiate between type 1 and type 2 AIT, a careful history and physical examination should be performed to identify pre-existing thyroid disease. An iodine-131 uptake test and colour flow Doppler sonography should be performed. Patients with type 2 AIT should receive a trial of glucocorticoids, whereas those with type 1 should receive antithyroid therapy. For patients in whom the mechanism of the thyrotoxicosis is unclear, a combination of prednisone and antithyroid therapy may be considered. PMID:19584973

Dronedarone: a promising alternative for the management of atrial fibrillation.

PubMed

Yalta, Kenan; Turgut, Okan Onur; Yilmaz, Mehmet Birhan; Yilmaz, Ahmet; Tandogan, Izzet

2009-10-01

Atrial fibrillation (AF) is the most frequently encountered chronic arrhythmia associated with significant morbidity. It is generally encountered in the elderly, and will presumably become more prevalent in the future due to the increasing proportion of the elderly in the population. Major studies on AF have demonstrated no significant difference between rhythm and rate control in terms of mortality. However, young population with new-onset or lone AF, or patients in whom the maintenance of sinus rhythm is a must (due to recurrent thromboembolic events etc.) still gives rise to significant concerns related to the obligatory long-term prophylaxis. The long-term administration of the currently available conventional agents (amiodarone, dofetilide, sotalol, propafenone,flecainide etc.) is considered as a 'double edged sword' due to the presence of life-threatening adverse effects including pro-arrhythmia and organ toxicity associated with these agents. Several molecules are being developed for the management of AF. However, only a few novel agents confer promising results with respect to safety and efficacy issues in the major studies. Dronedarone is an amiodarone analogue without iodine moiety in its structure, and is similar to amiodarone with regard to its structural and electrophysiological properties. Dronedarone is largely denuded of the potentially life-threatening adverse effects of anti-arrhythmics. Major clinical studies have demonstrated both rhythm and rate-controlling efficacy of dronedarone compared to placebo without any serious adverse effects in patients with AF. However, the ANDROMEDA trial, a large scale study including patients hospitalized for symptomatic congestive heart failure (with severely depressed left ventricular systolic functions) was prematurely terminated due to the increased mortality in the dronedarone arm compared to placebo indicating a lack of safety in this group of patients. Conversely, the recently published ATHENA study (including more than 4,600 high risk patients, but excluding those with severe heart failure) demonstrated a significant reduction in cardiovascular hospitalizations and cardiovascular mortality with dronedarone compared to placebo. In contrast, the DIONYSOS study, comparing dronedarone with amiodarone, demonstrated better safety, but lower efficacy of dronedarone for the maintenance of sinus rhythm in patients with AF. Further clinical trials (including head to head comparison with other conventional anti-arrhythmics) are still required to determine the place of dronedarone in the management of AF. The present review focuses on basic and clinical aspects of dronedarone, a novel agent for the management of AF.

The novel antiarrhythmic drug dronedarone: comparison with amiodarone.

PubMed

Kathofer, Sven; Thomas, Dierk; Karle, Christoph A

2005-01-01

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.

A benefit-risk assessment of class III antiarrhythmic agents.

PubMed

Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian; Sahebzadah, Naji; Køber, Lars

2002-01-01

With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone and dofetilide have their place as second-line therapy except for patients with heart failure where they are first line therapy being the only drugs where the safety has been documented for this group of high risk patients.

Addressing the management of atrial fibrillation - a systematic review of the role of dronedarone.

PubMed

Podda, Gian Marco; Casazza, Giovanni; Casella, Francesco; Dipaola, Franca; Scannella, Emanuela; Tagliabue, Ludovica

2012-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. It occurs in 1%-2% of the general population and its prevalence increases with age. Dronedarone, a noniodinated benzofuran similar to amiodarone, was developed as an antiarrhythmic agent for patients with atrial fibrillation. The aim of our systematic review was to critically evaluate randomized controlled trials that compared treatment with dronedarone versus placebo or amiodarone in patients with atrial fibrillation. Electronic databases (MEDLINE, Embase, and Central) were searched up to November 2011 with no language restrictions. We included randomized controlled trials in which dronedarone was compared to placebo or other drugs in patients with AF. Internal and external validity was assessed. We identified seven papers corresponding to eight randomized controlled trials. The DAFNE, EURIDIS/ADONIS, and ATHENA trials demonstrated a reduction of AF recurrence with dronedarone as compared to placebo in patients with nonpermanent AF. The DIONYSOS study showed that dronedarone is less effective for the prevention of recurrent AF but improved tolerability as compared to amiodarone. Considering patients with permanent AF, the ERATO trial showed that dronedarone had rate-control effects while the PALLAS study was stopped early since stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes were significantly more frequent in subjects treated with dronedarone as compared to placebo. The ANDROMEDA trial included patients with recent hospitalization for heart failure and was terminated early because of excess of deaths in the dronedarone group. Like most antiarrhythmic drugs, dronedarone reduces the recurrence of AF in patients with paroxysmal or persistent AF as compared to placebo. However, relapse rates in the first year of therapy are high. Moreover, dronedarone showed to be less effective than amiodarone. Finally, dronedarone should be avoided in patients with permanent AF and a high risk for cardiovascular events or severe congestive heart failure.

99mTc Sestamibi Thyroid Scan in Amiodarone-Induced Thyrotoxicosis Type I.

PubMed

Patel, Niraj R; Tamara, Luis A; Lee, Ho

2016-07-01

Amiodarone-induced thyrotoxicosis (AIT) type I describes inducement of clinical hyperthyroidism by excessive thyroidal iodine in the setting of latent Graves disease, and therapy differs from that used for AIT type II. A 65-year-old man previously on amiodarone for atrial fibrillation developed clinical hyperthyroidism. Diagnosis of AIT was made, but the type was not clear. Tc sestamibi thyroid scan showed diffusely increased uptake and retention in an enlarged thyroid gland, a pattern consistent with AIT type I. Methimazole was initiated and controlled the thyrotoxicosis. I iodide thyroid scan and uptake study performed later was consistent with Graves disease.

Hepatic Phospholipidosis Is Associated with Altered Hepatobiliary Function as Assessed by Gadoxetate Dynamic Contrast-enhanced Magnetic Resonance Imaging.

PubMed

Lenhard, Stephen C; Lev, Mally; Webster, Lindsey O; Peterson, Richard A; Goulbourne, Christopher N; Miller, Richard T; Jucker, Beat M

2016-01-01

To determine if amiodarone induces hepatic phospholipidosis (PLD) sufficient to detect changes in hepatobiliary transporter function as assessed by gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), rats were orally dosed with vehicle (1% methyl cellulose) or amiodarone (300 mg/kg/day) for 7 consecutive days. Gadoxetate DCE-MRI occurred at baseline, day 7, and following a 2-week washout of amiodarone. At day 7, the gadoxetate washout rate was significantly decreased compared to the vehicle group. Blood chemistry analysis revealed no significant changes in liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]/alkaline phosphatase [ALP]), bilirubin, or bile acids between vehicle or amiodarone groups. Hepatic PLD was confirmed in all rats treated with amiodarone at day 7 by transmission electron microscopy. Following the 2-week washout, there was no ultrastructural evidence of hepatic PLD in rats and the gadoxetate washout rate returned to baseline levels. This is the first study to show the application of gadoxetate DCE-MRI to detect hepatobiliary functional changes associated with PLD and offer a potential new technique with clinical utility in patients suspected of having PLD. These results also suggest PLD itself has functional consequences on hepatobiliary function in the absence of biomarkers of toxicity, given the cause/effect relationship between PLD and function has not been fully established. © The Author(s) 2015.

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery.

PubMed

Mitchell, L Brent

2011-01-01

Postoperative atrial fibrillation and atrial flutter (POAF) are the most common complications of cardiac surgery that require intervention or prolong intensive care unit and total hospital stay. For some patients, these tachyarrhythmias have important consequences including patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events including stroke, exposure to the risks of antiarrhythmic treatments, longer hospital stay, and increased health care costs. We conclude that prevention of POAF is a worthwhile exercise and recommend that the dominant therapy for this purpose be β-blocker therapy, especially the continuation of β-blocker therapy that is already in place. When β-blocker therapy is contraindicated, amiodarone prophylaxis is recommended. If both of these therapies are contraindicated, therapy with either intravenous magnesium or biatrial pacing is suggested. Patients at high risk of POAF may be considered for first-line amiodarone therapy, first-line sotalol therapy, or combination prophylactic therapy. The treatment of POAF may follow either a rate-control approach (with the dominant therapy being β-blocking drugs) or a rhythm-control approach. Anticoagulation should be considered if persistent POAF lasts >72 hours and at the point of hospital discharge. The ongoing need for any POAF treatment (including anticoagulation) should be reconsidered 6-12 weeks after the surgical procedure. Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

PubMed

Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F

1985-12-01

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation.

PubMed

Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk

2011-01-06

Atrial fibrillation (AF) is the most common sustained arrhythmia. Management of AF includes rate control, rhythm control if necessary, prevention of thromboembolic events, and treatment of the underlying disease. Rate control is usually achieved by pharmacological suppression of calcium currents or by applying β-blockers or digitalis compounds. In contrast, the number of compounds available for rhythm control is still limited. Class Ic agents increase mortality in patients with structural heart disease, and amiodarone harbors an extensive side effect profile despite its efficacy in maintaining sinus rhythm. Furthermore, rhythm control by these compounds has not been shown to reduce patient mortality. Dronedarone is a new anti-arrhythmic drug that has been developed to provide rhythm and rate control in AF patients with fewer side effects compared with amiodarone. This review primarily focuses on clinical trials evaluating efficacy and safety of the novel drug. Conclusions from these studies are critically reviewed, and recommendations for clinical practice are discussed. Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation (ATHENA trial). However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm (DIONYSOS trial) and is contraindicated in severe or deteriorating heart failure (ANDROMEDA trial). In summary, dronedarone represents a valuable addition to the limited spectrum of antiarrhythmic drugs and is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure.

Safety considerations in the pharmacological management of atrial fibrillation.

PubMed

Camm, A John

2008-07-21

The pharmacological management of atrial fibrillation (AF) requires careful consideration from a safety perspective. This article focuses primarily on maintenance therapy using antiarrhythmic drugs (AADs). The foremost safety issue for AADs is the propensity of class IA and III agents to cause torsade de pointes arrhythmias. Class IA drugs, particularly quinidine, can induce torsade de pointes at low or subtherapeutic doses, but higher doses are not necessarily associated with an increased incidence. 'Pure' class III drugs such as dofetilide induce torsade de pointes in a dose-related manner, but some class III agents with more complex actions such as amiodarone have a markedly lower potential to cause this arrhythmia. The risk of torsade de pointes precludes the use of class IA and 'pure' class III agents in patients with left ventricular hypertrophy and bradycardia. Class IC agents may cause sustained monomorphic ventricular tachycardias and are generally precluded in ischaemic and structural heart disease. Advanced heart failure patients may be treated with amiodarone or dofetilide, but most other AADs are unsuitable. The most important extracardiac toxicities occurring with AADs are those of amiodarone. Drug interactions are a significant safety issue in the management of AF, including pharmacokinetic interactions in which plasma levels of the AAD are raised - increasing the risk of proarrhythmia - and concomitant use of drugs that prolong the QT interval. Notwithstanding these considerations, most patients with AF can be considered for rhythm control, provided there is adequate pre-treatment assessment and protocols for initiation, dosing and monitoring are followed with care.

Antidysrhythmic agents at the turn of the twenty-first century: a current review.

PubMed

Haugh, Kathy Henley

2002-03-01

The use of class IA agents is gradually on the decline, primarily as a result of its unfavorable risk-to-benefit ratio. Lidocaine, a class IB agent, has been widely used in the acute treatment of VT. However, alternate drugs are being considered increasingly as first-line agents in the acute treatment of VT. Class IC drugs are contraindicated in patients with structural cardiac abnormalities and have a limited usefulness in the management of dysrhythmias. Beta-blockers continue to increase their role in cardiology, and subsequently their use in managing dysrhythmias. Class III agents, including amiodarone, sotalol, ibutilide, and dofetilide, are among the most widely used antidysrhythmics. Class IV calcium channel blockers have a limited usefulness in tachydysrhythmias. Digoxin and adenosine have unique antidysrhythmic properties and will likely retain their roles as antidysrhythmic agents. In the wake of the effectiveness of amiodarone, the drug that crosses all classes, some now question the benefit of pure agents that block a single, specific ion channel in the heart. After CAST8 demonstrated that antidysrhythmics can increase mortality while seemingly suppressing dysrhythmias, new drugs will continue to undergo intense scrutiny with regard to their efficacy, safety, and usefulness in treating dysrhythmias.

Comparison of the cardiac electrophysiology and general toxicology of two formulations of intravenous amiodarone in dogs.

PubMed

Cushing, Daniel J; Cooper, Warren D; Gralinski, Michael R; Lipicky, Raymond J; Kudenchuk, Peter J; Kowey, Peter R

2009-09-01

Intravenous amiodarone (AIV) must be administered slowly after dilution to avoid hypotension, which is due to the cosolvents polysorbate 80 and benzyl alcohol used in its formulation. PM101 is a formulation of amiodarone devoid of these cosolvents, which enables bolus administration. We evaluated any potential toxicity or exaggerated adverse cardiac electrophysiologic effects of PM101 compared with AIV and control. Beagle dogs were treated with the human-equivalent amiodarone loading dose (2.14 mg/kg) with PM101 (bolus push) or AIV (10 min infusion in the toxicology study and bolus push in the electrophysiology study) followed by maintenance infusion (0.014 mg kg(-1) min(-1) through 6 h followed by 0.007 mg kg(-1) min(-1) through 14 days) or a control. General toxicology was assessed in conscious dogs over 14 days. Cardiac electrophysiology was assessed in a separate cohort of anesthetized dogs during the first 20 min of dosing. In the toxicology study, dosing in all animals in the AIV group was terminated within 17 min of initiation due to a severe hypersensitivity reaction. There were no acute adverse clinical signs in the PM101 or control groups. There were no significant effects on body weight or ECG parameters, and no adverse histomorphologic changes were seen in dogs that received PM101 or AIV. No significant exaggerated cardiac electrophysiologic effects of the approved doses PM101 or AIV were observed. PM101 may represent a formulation of intravenous amiodarone that could be administered rapidly without dilution in the setting of life-threatening cardiac arrhythmias.

The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism

PubMed Central

Gessner, Guido; Macianskiene, Regina; Starkus, John G.; Schönherr, Roland; Heinemann, Stefan H.

2010-01-01

Human ether à go-go related gene (hERG1) potassium channels underlie the repolarizing IKr current in the heart. Since they are targets of various drugs with cardiac side effects we tested whether the amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) blocks hERG1 channels like its parent compound. Using patch-clamp and two-electrode voltage-clamp techniques we found that KB130015 blocks native and recombinant hERG1 channels at high voltages, but it activates them at low voltages. The activating effect has an apparent EC50 value of 12 μM and is brought about by an about 4-fold acceleration of activation kinetics and a shift in voltage-dependent activation by −16 mV. Channel activation was not use-dependent and was independent of inactivation gating. KB130015 presumably binds to the hERG1 pore from the cytosolic side and functionally competes with hERG1 block by amiodarone, E4031 (N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl] -4-piperidinyl] carbonyl] phenyl] methanesulfonamide dihydrochloride), and sertindole. Vice versa, amiodarone attenuates hERG1 activation by KB130015. Based on synergic channel activation by mallotoxin and KB130015 we conclude that the hERG1 pore contains at least two sites for activators that are functionally coupled among each other and to the cavity-blocker site. KB130015 and amiodarone may serve as lead structures for the identification of hERG1 pore-interacting drugs favoring channel activation vs. block. PMID:20097192

Amiodarone-induced myxoedema coma.

PubMed

Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

2014-04-12

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3-5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.

Class III antiarrhythmic agents in cardiac failure: lessons from clinical trials with a focus on the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).

PubMed

Doval, H C

1999-11-04

The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other therapeutic interventions, and should help to clarify the optimal management strategy for patients with underlying heart failure.

Amiodarone-induced myxoedema coma

PubMed Central

Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

2014-01-01

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3–5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8–1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25–756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease. PMID:24729111

The effects of pure potassium channel blocker nifekalant and sodium channel blocker mexiletine on malignant ventricular tachyarrhythmias.

PubMed

Otuki, Sou; Hasegawa, Kanae; Watanabe, Hiroshi; Katsuumi, Goro; Yagihara, Nobue; Iijima, Kenichi; Sato, Akinori; Izumi, Daisuke; Furushima, Hiroshi; Chinushi, Masaomi; Aizawa, Yoshifusa; Minamino, Tohru

Patients with repetitive ventricular tachyarrhythmias - so-called electrical storm - frequently require antiarrhythmic drugs. Amiodarone is widely used for the treatment of electrical storm but is ineffective in some patients. Therefore, we investigated the efficacy of stepwise administration of nifekalant, a pure potassium channel blocker, and mexiletine for electrical storm. This study included 44 patients with repetitive ventricular tachyarrhythmias who received stepwise therapy with nifekalant and mexiletine for electrical storm. Nifekalant was initially administered, and mexiletine was subsequently added if nifekalant failed to control ventricular tachyarrhythmias. Nifekalant completely suppressed recurrences of ventricular arrhythmias in 28 patients (64%), including 6 patients in whom oral amiodarone failed to control arrhythmias. In 9 of 16 patients in whom nifekalant was partially effective but failed to suppress ventricular arrhythmias, mexiletine was added. The addition of mexiletine prevented recurrences of ventricular tachyarrhythmias in 5 of these 9 patients (56%). There was no death associated with electrical storm. In total, the stepwise treatment with nifekalant and mexiletine was effective in preventing ventricular tachyarrhythmias in 33 of 44 patients (75%). There was no difference in cycle length of the ventricular tachycardia, QRS interval, QT interval, or left ventricular ejection fraction between patients who responded to antiarrhythmic drugs and those who did not. During follow-up, 8 patients had repetitive ventricular tachyarrhythmia recurrences, and the stepwise treatment was effective in 6 of these 8 patients (75%). The stepwise treatment with nifekalant and mexiletine was highly effective in the suppression of electrical storm. Copyright © 2016. Published by Elsevier Inc.

Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

PubMed

Santangeli, Pasquale; Zado, Erica S; Supple, Gregory E; Haqqani, Haris M; Garcia, Fermin C; Tschabrunn, Cory M; Callans, David J; Lin, David; Dixit, Sanjay; Hutchinson, Mathew D; Riley, Michael P; Marchlinski, Francis E

2015-12-01

Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO-EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56±44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on β-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs. © 2015 American Heart Association, Inc.

Macrocytic anemia and thrombocytopenia induced by orlistat.

PubMed

Palacios-Martinez, David; Garcia-Alvarez, Juan Carlos; Montero-Santamaria, Nieves; Villar-Ruiz, Olga Patricia; Ruiz-Garcia, Antonio; Diaz-Alonso, Raquel Asuncion

2013-10-01

The overall incidence of obesity and its prevalence is increasing continuously. The obesity is a cardiovascular risk factor whose importance is increasing too. It is associated with many chronic conditions such as type II diabetes mellitus or cardiovascular diseases. The obesity is also implicated as a risk factor for several kinds of cancer such as esophagus, pancreas, colon, rectum, breast cancer in menopausal women. The treatment of the obesity may reduce the incidence of these diseases. The mainstray of the treatment of obesity is changing the lifestyles, but obesity´s treatment may need drug therapy or even though surgical treatment. Orlistat is a specific inhibitor of gastrointestinal lipases, which stops fat absortion. It is used along with a hypocaloric diet, for obesity´s treatment. The beneficial effects of orlistat include weight loss, the improvement of blood pressure´s control, it may delay the development of diabetes mellitus, and it may reduce HbA1c. Besides the interaction with other drugs (mainly warfarin and amiodarone). Orlistat´s mainly side effects are gastrointestinal disorders such as the existence of oily spotting from the rectum, abdominal pain or discomfort, fecal urgency. There are also side effects at other levels, like flu symptoms, hypoglycemia, heathache or upper respiratory infections. There are other side effects with very low incidence but clinically relevant like pancreatitis, subacute liver failure, severe liver disease, myopathy, or tubular necrosis secondary to oxalate nephropathy induced by Orlistat. IN THIS CASE REPORT APPEARS A NEW ADVERSE EFFECT OF ORLISTAT THAT HAS NOT BEEN DESCRIBED ABOVE: thrombopenia and macrocytic anemia.

Efficacy of topical chamomile on the incidence of phlebitis due to an amiodarone infusion in coronary care patients: a double-blind, randomized controlled trial.

PubMed

Sharifi-Ardani, Maryam; Yekefallah, Leili; Asefzadeh, Saeed; Nassiri-Asl, Marjan

2017-09-01

Amiodarone is a useful antiarrhythmic drug. Phlebitis, caused by intravenous amiodarone, is common in patients in coronary care units (CCUs). The aim of this study was to evaluate the effect of topical chamomile on the incidence of phlebitis due to the administration of an amiodarone infusion into the peripheral vein. This was a randomized, double-blind clinical trial, conducted on 40 patients (n = 20 per group) in two groups-an intervention group (chamomile ointment) and a control group (lanoline, as a placebo), hospitalized in the CCUs and undergoing an amiodarone infusion into the peripheral vein over 24 h. Following the cannulation and commencement of the infusion, placebo or chamomile ointment was rubbed in, up to 10 cm superior to the catheter and repeated every eight hours for three days. The cannula site was then assessed based on the phlebitis checklist. The incidence and time of occurrence of phlebitis, relative risk, severity of phlebitis were the main outcome measures. Nineteen patients (19/20) in the control group had phlebitis on the first day of the study and one patient (20/20) on the second day. In the intervention group, phlebitis occurred in 13 cases (13/20) on the first day and another two (2/7) was found on the second day. The incidence of phlebitis was significantly different between two groups (P = 0.023). The cumulative incidence of phlebitis in the intervention group (15/20) is significantly later and lower than that in the control group (20/20) during two days (P = 0.008). Two patients in the intervention group did not develop phlebitis at all during the 3-day study. Also, the relative risk of phlebitis in the two groups was 0.68 (P = 0.008 5). A significant difference was not observed with regard to phlebitis severity in both groups. It seems that phlebitis occurred to a lesser extent and at a later time frame in the intervention group compared to control group. Topical chamomile may be effective in decreasing the incidence of phlebitis due to an amiodarone infusion. This protocol was registered in the Iranian Registry of Clinical Trials (IRCT2014042017361N1).

A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80.

PubMed

Munoz, A; Karila, P; Gallay, P; Zettelmeier, F; Messner, P; Mery, M; Grolleau, R

1988-02-01

In 20 patients undergoing coronary arteriography, the hemodynamic effects of an experimental preparation of i.v. amiodarone 5 mg kg-1 without Tween 80 (N) (10 patients) were compared with those of the commercial form with Tween 80 (A) (10 patients). Analysis of variance demonstrated differences during the 3 min of injection and for 3 min afterwards: left ventricular systolic pressure decreased from 110 + 11 to 86 +/- 11 mmHg (P = 0.001) after A and from 114 +/- 22 to 106 +/- 19 (P = 0.05) after N (comparison P = 0.01) while related tachycardia was also more pronounced after A (comparison P = 0.001). Left ventricular end diastolic pressure transiently decreased after A while continuously increasing after N (P = 0.05). During the following 30 min both A and N caused similar bradycardia, increase in ventricular filling pressure, vascular resistance and decrease in cardiac and contractility indexes. Amiodarone blood levels were similar after A or N. These data document a significant initial short duration vasoplegia, mainly related to Tween 80, after A, when amiodarone itself after producing a similar very slight effect causes bradycardia, and a moderate and progressive negative inotropic effect. It was concluded that while the experimental form would be of interest, the risk of severe hypotension after i.v. Cordarone can be largely avoided by using a slower rate of infusion, especially in patients with hypovolemic status.

[Thyroid and cardiovascular disorders].

PubMed

Zyśko, Dorota; Gajek, Jacek

2004-05-01

In this study three problems concerning interactions between thyroid and cardiovascular system are discussed. Cardiac arrhythmias, congestive heart failure, pleural effusion, hyperlipidaemia, arterial hypertension may be consequences of thyroid disorders leading to inappropriate hormone secretion. During such illnesses as heart failure, myocardial infarction and in patients undergoing coronary artery bypass surgery profound changes may occur in thyroid hormone metabolism known as sick euthyroid syndrome. Treatment with amiodarone may lead to changes in thyroid tests results and to development of hypothyroidism or thyrotoxicosis.

Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias.

PubMed

Verduyn, S C; Vos, M A; Leunissen, H D; van Opstal, J M; Wellens, H J

1999-02-01

In the anesthetized dog with complete chronic AV block (CAVB), we evaluated and compared the acute electrophysiologic effects of dronedarone i.v. (Dron, 2 times 2.5 mg/kg/10 min) and amiodarone i.v. (Amio, 2 times 5 mg/kg/10 min). This canine model with a high sensitivity for acquired torsade de pointes (TdP) provides an ideal substrate to evaluate ventricular repolarization abnormalities. Six ECG leads and two endocardial monophasic action potential (MAP) recordings in the left and right ventricle (LV and RV) were simultaneously recorded to measure QT time, action-potential duration (APD), interventricular dispersion (deltaAPD = LV(APD) - RV(APD)), early afterdepolarizations (EADs), ectopic beats (EBs), and TdP. Measurements were made at the spontaneous idioventricular rhythm (IVR) and 1,000-ms steady-state pacing. To investigate its short-term, antiarrhythmic properties, Dron was given after almokalant (0.12 mg/kg)-induced TdP. Furthermore, in another set of experiments, oral Dron (20 mg/kg, b.i.d) was given for 3 weeks to conscious CAVB dogs. Dron, i.v., shortened ventricular repolarization (QT, 435 +/- 60 to 360 +/- 55; LV(APD) 395 +/- 75 to 335 +/- 60 ms; p < 0.05), whereas IVR and ventricular effective refractory period (VERP, 225 +/- 30 to 230 +/- 30 ms) remained similar. Therefore the VERP/QT ratio increased (0.55 +/- 0.04 to 0.61 +/- 0.03; p < 0.05). Similar results were obtained with Amio, i.v.. Almokalant-induced TdP was characterized by an increased repolarization duration, deltaAPD, and EADs. Dron, i.v., suppressed the EADs, EBs, and TdP by a reduction and homogenization of repolarization (LV(APD), 505 +/- 110 to 455 +/- 80 ms, and deltaAPD, 110 +/- 55 to 65 +/- 40 ms). Long-term oral Dron increased the PP interval, CL-IVR, and QT(c) time. In contrast to oral treatment, Dron i.v. shortens ventricular repolarization parameters, resulting in suppression of EAD-dependent acquired TdP. The increased VERP/QT ratio after Dron i.v. may indicate an important second antiarrhythmic property.

Aconite poisoning with arrhythmia and shock.

PubMed

Tak, Sandeep; Lakhotia, Manoj; Gupta, Alok; Sagar, Amit; Bohra, Gopal; Bajari, Rajesh

2016-09-01

A 55-year-old male presented with history of nausea, vomiting, palpitation paresthesis and profuse sweating in emergency department 2h after ingestion of "Bachnaag" (Aconite) root. Examination revealed shock with irregular pulses. Initial ECG showed frequent multifocal ventricular ectopics (VE), which later turned to short runs of ventricular tachycardia (VT). Immediate gastric lavage was done and activated charcoal given. Patient was treated with fluid resuscitation without any improvement in blood pressure. Patient was started on nor-adrenaline infusion with gradual recovery from hypotension over a period of 6h, but support was continued for 48h. Amiodarone was started to control ventricular excitability, which persisted over 72h with gradual decrease in frequency of VT and VE. Patient was discharged with normal sinus rhythm on oral amiodarone on 5th day of hospitalization. On follow-up after 2 weeks patient was totally asymptomatic and amiodarone was stopped. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Ultraviolet photography of the in vivo human cornea unmasks the Hudson-Stähli line and physiologic vortex patterns.

PubMed

Every, Sean G; Leader, John P; Molteno, Anthony C B; Bevin, Tui H; Sanderson, Gordon

2005-10-01

To perform ultraviolet (UV) macrophotography of the normal in vivo human cornea, establishing biometric data of the major component of UV absorption for comparison with the Hudson-Stähli (HS) line, the distribution of iron demonstrated by Perl stain, and cases of typical amiodarone keratopathy. Nonrandomized comparative case series of UV photographs of 76 normal corneas (group 1) and 16 corneas with typical amiodarone keratopathy (group 2). Image-analysis software was used to grade the major component of UV absorption for slope and the coordinates of its points of intersection with the vertical corneal meridian and inflection. In group 1 the major component had a mean slope of 5.8 degrees, sloping down from nasal to temporal cornea. The mean coordinates of points of intersection with the vertical corneal meridian and inflection were (0, 0.30) and (0.02, 0.31), respectively. No significant differences between groups 1 and 2 were found for slope (P = 0.155), intersection with the vertical corneal meridian (P = 0.517), and point of inflection (P = 0.344). The major component of UV absorption was consistent with published characteristics of the HS line, and coincidence of UV absorption and Perl-stained iron was demonstrated in one corneal button. A vortex pattern of UV absorption was observed in all corneas. UV photography demonstrates subclinical corneal iron, confirming its deposition in an integrated HS line/vortex pattern. Coincident iron and amiodarone deposition occurs in amiodarone keratopathy.

The role of negatively charged lipids in lysosomal phospholipase A2 function

PubMed Central

Abe, Akira; Shayman, James A.

2009-01-01

Lysosomal phospholipase A2 (LPLA2) is characterized by increased activity toward zwitterionic phospholipid liposomes containing negatively charged lipids under acidic conditions. The effect of anionic lipids on LPLA2 activity was investigated. Mouse LPLA2 activity was assayed as C2-ceramide transacylation. Sulfatide incorporated into liposomes enhanced LPLA2 activity under acidic conditions and was weakened by NaCl or increased pH. Amiodarone, a cationic amphiphilic drug, reduced LPLA2 activity. LPLA2 exhibited esterase activity when p-nitro-phenylbutyrate (pNPB) was used as a substrate. Unlike the phospholipase A2 activity, the esterase activity was detected over wide pH range and not inhibited by NaCl or amiodarone. Presteady-state kinetics using pNPB were consistent with the formation of an acyl-enzyme intermediate. C2-ceramide was an acceptor for the acyl group of the acyl-enzyme but was not available as the acyl group acceptor when dispersed in liposomes containing amiodarone. Cosedimentation of LPLA2 with liposomes was enhanced in the presence of sulfatide and was reduced by raising NaCl, amiodarone, or pH in the reaction mixture. LPLA2 adsorption to negatively charged lipid membrane surfaces through an electrostatic attraction, therefore, enhances LPLA2 enzyme activity toward insoluble substrates. Thus, anionic lipids present within lipid membranes enhance the rate of phospholipid hydrolysis by LPLA2 at lipid-water interfaces.—Abe, A., and J. A. Shayman. The role of negatively charged lipids in lysosomal phospholipase A2 function. PMID:19321879

Dronedarone.

PubMed

Hoy, Sheridan M; Keam, Susan J

2009-08-20

Oral dronedarone is a non-iodinated benzofurane derivative structurally related to amiodarone. Although it is considered a class III antiarrhythmic agent like amiodarone, it demonstrates multi-class electrophysiological activity. Data from the ATHENA study demonstrated that patients receiving oral dronedarone 400 mg twice daily for 12-30 months had a significantly lower risk of experiencing first hospitalization due to a cardiovascular event or death from any cause than those receiving placebo. Dronedarone exhibited rate- and rhythm-controlling properties in patients with atrial fibrilation (AF) or atrial flutter, significantly reducing the risk of a first recurrence of AF versus placebo following 12 months' therapy in the ADONIS and EURIDIS studies. In the ERATO study, dronedarone was also significantly more effective than placebo in terms of ventricular rate control. Furthermore, the beneficial effects of oral dronedarone on ventricular rate control were maintained during exercise and sustained with continued therapy. Oral dronedarone was generally well tolerated in the treatment of adult patients with AF and/or atrial flutter in clinical studies. The incidence of diarrhoea, nausea, bradycardia, rash and QT-interval prolongation was significantly higher with oral dronedarone than placebo in the large ATHENA study; however, serious cardiac-related adverse events were observed in <1% of oral dronedarone recipients.

A review of the appropriate and inappropriate use of dronedarone: lessons learned from controlled studies and regulatory submission.

PubMed

Naccarelli, Gerald V; Wolbrette, Deborah L; Samii, Soraya; Banchs, Javier E; Penny-Peterson, Erica; Gonzalez, Mario D

2010-12-01

Dronedarone is a multichannel blocker with electrophysiologic effects similar to amiodarone. Dronedarone has been documented to prevent atrial fibrillation recurrences and also has efficacy in slowing the ventricular response during episodes of atrial fibrillation. However, in the ANDROMEDA trial, dronedarone was associated with increased mortality when tested in New York Heart Association (NYHA) III/IV patients with left ventricular ejection fractions of less than 35%, who also had a recent hospitalization for decompensated heart failure. When such high-risk patients with heart failure were excluded in the ATHENA trial, dronedarone treatment resulted in a statistical reduction in the composite primary end point of all-cause mortality or cardiovascular hospitalization. In ATHENA, dronedarone reduced cardiovascular hospitalizations even though in the DIONY-SOS trial dronedarone had less effect than amiodarone on suppressing atrial fibrillation recurrences. The most appropriate patients for treatment with dronedarone would be patients with a recent history of paroxysmal or persistent atrial fibrillation/atrial flutter (AF/AFL) that have associated risk factors per the inclusion criteria of ATHENA. Inappropriate patients would be those with class IV heart failure or recently hospitalized for heart failure within the last month from an acute decompensation, the main inclusion criteria in ANDROMEDA. Dronedarone is a novel, multichannel blocking antiarrhythmic agent that may have some pleiotropic effects in addition to its ability to suppress and maintain sinus rhythm and control the rate during AF/AFL recurrences.

Association Between Use of Non–Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation

PubMed Central

Chang, Shang-Hung; Chou, I-Jun; Yeh, Yung-Hsin; Chiou, Meng-Jiun; Wen, Ming-Shien; Kuo, Chi-Tai; See, Lai-Chu

2017-01-01

Importance Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs. PMID:28973247

Management of atrial fibrillation in the post-cardiac surgery setting.

PubMed

Daoud, Emile G

2004-02-01

New onset postcardiac surgery AF is a prevalent problem associated with increased morbidity, hospital expense, and length of stay. Those agents that inhibit beta-adrenergic receptors (class II beta-blockers, sotalol, and amiodarone) have been demonstrated to be successful prophylaxis against postoperative AF. Furthermore, those therapies that do not inhibit beta-receptors are not effective prophylactic agents. Until comparative trials demonstrate a significant reduction in postoperative AF without additional adverse effects for sotalol or amiodarone compared with beta-blockers, class II beta-blockers are the preferred prophylactic therapy. If patients are deemed unable to take beta-blockers, amiodarone is likely the best alternative. Although prophylaxis against postoperative AF seems prudent, the impact of prophylactic therapy on length of stay and hospital costs has not been a primary objective of any randomized trial. Furthermore, no studies have compared prophylactic therapy for every patient versus therapy only for those patients who experience AF after heart surgery. In the absence of data from randomized clinical trials, postoperative AF should be managed in a similar fashion to clinical AF with attention to rate control, anticoagulation, and restoration of sinus rhythm.

Pharmacotherapy Evaluation and Utilization in Coronary Artery Bypass Grafting Patients in Kosovo during the Period 2016-2017

PubMed Central

Daci, Armond; Bozalija, Adnan; Cavolli, Raif; Alaj, Rame; Beretta, Giangiacomo; Krasniqi, Shaip

2018-01-01

BACKGROUND: Coronary Artery Bypass Grafting (CABG) is realised in patients with critical or advanced disease of coronary arteries. There are different pharmacotherapeutic approaches which are used as management, treatment and preventive therapy in cardiovascular disease or related comorbidities. Performing a successful surgery, pharmacotherapy, and increase of bypass patency rate remains a serious challenge. AIM: This study aims to analyse the patient characteristics undergoing CABG and evaluation of their drug utilisation rate and daily dosages in the perioperative period. MATERIAL AND METHODS: Data were collected from 102 patients in the period 2016-2017 and detailed therapeutic prescription and dosages, patient characteristics were analysed before the operation, after the operation and visit after operation in the Clinic of Cardiac surgery-University Clinical Center of Kosovo. RESULTS: Our findings had shown that patients provided to have normal biochemical parameters in the clinic before the operation, and were related to cardiovascular diseases and comorbidities and risk factors with mainly elective intervention. The, however, higher utilisation of cardiovascular drugs such as beta blockers, diuretics, anticoagulants, statins and lower calcium blockers, ACEi, ARBs, hydrochlorothiazide, amiodarone were founded. ARBs, beta blockers, statins, nitrates and nadroparin utilisation decreased after operation and visit after the operation, whereas amiodarone only in the visit after the operation. Diuretics are increased after the operation which decreases in the visit after the operation. Regarding the daily dosage, only metoprolol was increased in the visit after operation (P < 0.001) and visit after operation (P < 0.05) whereas losartan and furosemide were increased (P < 0.01) and (P < 0.05) respectively. CONCLUSION: The study showed that beta blockers, statins, aspirin, nitrates (before the operation), furosemide and spironolactone are the most utilised drugs. However, we found low utilisation rate for ACEi, ARBs, clopidogrel, nadroparin, warfarin, xanthines, amiodarone, calcium blockers. Daily dosages were different compared to before CABG only in metoprolol, losartan, and furosemide. PMID:29610608

Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

PubMed

Wu, Chuntao; Tcherny-Lessenot, Stephanie; Dai, Wanju; Wang, Yunxun; Kechemir, Hayet; Gandhi, Sampada; Lin, Stephen; Juhaeri, Juhaeri

2018-03-01

There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Behaviour of five pharmaceuticals with high baseline toxicity in wastewater treatment

NASA Astrophysics Data System (ADS)

van Driezum, Inge; McArdell, Christa; Fenner, Kathrin; Helbling, Damian; van Breukelen, Boris

2013-04-01

Many pharmaceuticals enter the aquatic environment through sewer systems and are partially removed in wastewater treatment plants (WWTP) by sorption to sludge biomass or biodegradation. Biodegradation often does not lead to complete mineralization but to the formation of stable transformation products (TPs), which might still be harmful to the environment. Recently, a study was undertaken to assess the risk of the top 100 pharmaceuticals from wastewater of a hospital in Switzerland. The predicted toxicity was linked to the predicted environmental concentration in order to assess overall risk potential. In this study, biodegradation and sorption studies were carried out on the top five selected pharmaceuticals (amiodarone, atorvastatin, clotrimazole, meclozine and ritonavir). Potential TPs that are formed during activated sludge treatment were identified and concentrations of both the parent compounds and TPs were measured in the WWTP. With this data, the fate of these compounds was modeled in a WWTP system using a multi-reactor steady-state WWTP model. This study showed that sorption was the most important loss process for amiodarone and meclozine. They had an elimination of more than 99%. Sorption was also the main loss process for clotrimazole, but it was combined with some biodegradation. For ritonavir, both biodegradation and sorption played a role in the loss of this compound. The most important removal process for atorvastatin was biodegradation. Four TPs, formed through β-oxidation and monohydroxilation, were identified in both the activated sludge batch reactors and the WWTP effluent. In the WWTP effluent, only atorvastatin, clotrimazole and ritonavir were found. All identified TPs of atorvastatin were detected in the effluent. Risk quotients (RQ) of all five pharmaceuticals were estimated based on effluent concentration and baseline toxicity and ranged from zero to 2.14. Only ritonavir potentially poses an ecotoxicological risk for the aquatic environment.

Comparative effects of rapid bolus administration of aqueous amiodarone versus 10-minute cordarone I.v. infusion on mean arterial blood pressure in conscious dogs.

PubMed

Somberg, John Charin; Cvetanovic, Ivana; Ranade, Vasant; Molnar, Janos

2004-09-01

This study was designed to test the hypothesis that rapid bolus administration of an aqueous formulation of intravenous amiodarone causes less hypotension than a 10-minute infusion of the standard formulation, Cordarone IV. Hypotension was the most common adverse event reported with Cordarone IV. The hypotension was not dose related, but related to the rate of infusion. Therefore, product labeling calls Cordarone and its generic formulations to be administered over 10 minutes. Cordarone IV contains polysorbate 80 and benzyl alcohol, each causes hypotension. A new aqueous formulation of amiodarone (Amio-Aqueous) does not contain these agents and therefore may cause less hypotension. Six conscious beagle dogs were instrumented with a telemetric device for blood pressure monitoring. The study was conducted on 5 days. On the first 2 days, a 10-min infusion or a bolus of D(5)W was administered (placebo). Over the following 3 days, the dogs received (in randomized order, one per day) a 10-min infusion of 2.5 mg/kg Cordarone IV and boluses of 2.5 mg/kg and 5.0 mg/kg Amio-Aqueous injected over 2 to 5 sec. The dogs were monitored for 2 hrs after dosing. Compared to placebo, boluses of aqueous amiodarone produced no significant changes in the mean arterial blood pressure (MABP). In contrast, Cordarone infusion produced significant decreases in MABP that lasted for at least 2 hrs (p < 0.001). Amio-Aqueous had significantly better hemodynamic profile permitting rapid intravenous administration. This is a significant advantage over the standard formulation, because Cordarone cannot be administered by rapid bolus due to excipient-related hypotension.

Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

PubMed

Anderson, J L

1995-10-01

Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

Race influences warfarin dose changes associated with genetic factors

PubMed Central

Brown, Todd M.; Yan, Qi; Thigpen, Jonathan L.; Shendre, Aditi; Liu, Nianjun; Hill, Charles E.; Arnett, Donna K.; Beasley, T. Mark

2015-01-01

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P = .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race. PMID:26024874

Race influences warfarin dose changes associated with genetic factors.

PubMed

Limdi, Nita A; Brown, Todd M; Yan, Qi; Thigpen, Jonathan L; Shendre, Aditi; Liu, Nianjun; Hill, Charles E; Arnett, Donna K; Beasley, T Mark

2015-07-23

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P = .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race. © 2015 by The American Society of Hematology.

Hepatic and renal failure associated with amiodarone infusion in a patient with hereditary fructose intolerance.

PubMed

Curran, B J; Havill, J H

2002-06-01

Hereditary fructose intolerance is a rare inherited metabolic disorder. Although fructose intolerance usually presents in the paediatric age group, individuals can survive into adulthood by self.manipulation of diet. Hospitalisation can become a high.risk environment for these individuals because of loss of control of their strict dietary constraints and the added danger of administration of medications containing fructose, sucrose and sorbitol. We report a case of hereditary fructose intolerance in an adult presenting with hepatic and renal failure associated with an amiodarone infusion and explore the possibility of polysorbate 80 as a cause of this patient's hepatic and renal failure.

A challenging broad-complex tachycardia.

PubMed

Iyer, Nithin Ramesh; Oomen, Adrianus W G J; Sy, Raymond W

2018-01-01

A 53-year-old man presented with chest pain, palpitations and presyncope, without history of overt cardiac disease. The patient was alert. His heart rate was 206 beats per minute, and his blood pressure was 100/50 mm Hg. An intravenous bolus of amiodarone 150 mg was administered in the emergency department. His ECGs preamiodarone and postamiodarone are shown in figure 1. Echocardiography showed low-normal left ventricular systolic function.Figure 1(A) ECG of index arrhythmia. (B) ECG following amiodarone. What should the next diagnostic test be?Referral for electrophysiology study.Referral for urgent coronary angiography.12-lead ECG with posterior lead placement.Bedside adenosine challenge.

Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog.

PubMed

Masini, E; Planchenault, J; Pezziardi, F; Gautier, P; Gagnol, J P

1985-09-01

The solvent of commercial amiodarone (Polysorbate 80) has been reported to produce haemodynamic responses in humans and in dogs similar to those produced by histamine infusion. We therefore evaluated the correlation between hypotension induced by the solvent of amiodarone and its histamine-releasing properties in the awake dog. The solvent of amiodarone administered to a dog, over 5 min in a dose of 10 mg/kg of Polysorbate 80, produced severe hypotension after the first administration; the second injection (24 h later) caused fewer hypotensive effects. Histamine release in the peripheral tissues was demonstrated by a marked increase in plasma histamine concentrations, with the maximum value 10 min after the solvent administration. H1- and H2-receptor blockade with mepyramine (5 mg/kg) and cimetidine (10 mg/kg) significantly reduced the cardiovascular effects of the solvent. Isolated peritoneal mast cells from rats also released histamine in response to Polysorbate 80. These studies show that Polysorbate 80 releases histamine both in vitro and in isolated mast cells from rats and in vivo in the dog, and that the plasma concentrations are correlated with the haemodynamic responses.

Pharmacological therapy in children with nodal reentry tachycardia: when, how and how long to treat the affected patients.

PubMed

Bouhouch, R; El Houari, T; Fellat, I; Arharbi, M

2008-01-01

Atrio-ventricular nodal reentrant tachycardia (AVNRT) is a rare supra-ventricular tachycardia (SVT) in children and becomes more frequent in adolescents. Most of children with an AVNRT have a healthy heart thus rarely experiencing severe symptoms. Because of haemodynamic instability or risk of complications, recurrences of SVT may require a chronic therapy. Interruption of dual atrio-ventricular nodal physiology is the basic mechanism to terminate AVNRT. This may be achieved by using anti-arrhythmic drugs or through Radiofrequency catheter ablation (RF). We aim to review the literature on the use of anti-arrhythmic drugs for the management of AVNRT in children aged more than 1 year and discuss the recommended dosages and the duration of a long term therapy. In the absence of comparative trials of risks and benefits between pharmacological therapy and RF and because of a greater clinical experience with anti-arrhythmic drugs, these last but not the least continue to be first-line therapy in the management of most SVT in children. Trials on pharmacotherapy in children with SVT in general and AVNRT in particular are lacking, use of anti-arrhythmic drugs being extrapolated from adult literature. Although Adenosine is becoming more used since it is the safest and effective drug in the acute setting, Digoxin continue to be the drug of first choice. Beta-blockers and Class I anti-arrhythmic are the second choice drugs with Flecainide being the preferred anti-arrhythmic drug for treatment failures. Amiodarone is rarely used as a chronic therapy in resistant cases. With the new advances in the RF technology, this therapy is becoming more safe and effective for AVNRT in children. Therefore, additional well-designed controlled trials are needed to further evaluate the comparative efficacy of anti-arrhythmic drugs in the management of AVNRT in children, as well as to evaluate dosing and toxicity in various age groups and determine the duration of a chronic therapy as compared to a potential RF.

Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

PubMed

Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

2015-01-01

Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

PubMed

Nishtala, P S; Chyou, T-Y

2017-04-01

Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals RESULTS AND DISCUSSION: Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17-4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55-4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86-13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61-1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19-2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83-3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse. © 2016 John Wiley & Sons Ltd.

Experimental and early investigational drugs for angina pectoris.

PubMed

Elgendy, Islam Y; Winchester, David E; Pepine, Carl J

2016-12-01

Ischemic heart disease (IHD) is a major cause of death and disability among Western countries and angina pectoris is the most prevalent symptomatic manifestation. Strategies to improve management of chronic stable angina are a priority. Areas covered: A comprehensive review was conducted using the Medline and Cochrane databases as well as the clinical trial databases in the United States and Europe. Traditional therapies for angina will be discussed. This review particularly emphasizes investigational therapies for angina (including pharmacological agents, cell and gene based therapies, and herbal medications). Expert opinion: There has been renewed interest in older anti-angina agents (e.g., perhexiline, amiodarone, and phosphodiestrase-5 inhibitors). Other anti-inflammatory agents (e.g., allopurinol and febuxostat) are currently undergoing evaluation for angina therapy. Therapeutic angiogenesis continues to face some challenges. Future trials should evaluate the optimum patient population that would benefit from this form of therapy.

Experimental and early investigational drugs for angina pectoris

PubMed Central

Elgendy, Islam Y.; Winchester, David E.; Pepine, Carl J.

2016-01-01

Introduction Ischemic heart disease (IHD) is a major cause of death and disability among Western countries and angina pectoris is the most prevalent symptomatic manifestation. Strategies to improve management of chronic stable angina are a priority. Areas covered A comprehensive review was conducted using the Medline and Cochrane databases as well as the clinical trial databases in the United States and Europe. Traditional therapies for angina will be discussed. This review particularly emphasizes investigational therapies for angina (including pharmacological agents, cell and gene based therapies, and herbal medications). Expert commentary There has been renewed interest in older anti-angina agents (e.g., perhexiline, amiodarone, and phosphodiestrase-5 inhibitors). Other anti-inflammatory agents (e.g., allopurinol and febuxostat) are currently undergoing evaluation for angina therapy. Therapeutic angiogenesis continues to face some challenges. Future trials should evaluate the optimum patient population that would benefit from this form of therapy. PMID:27791405

Dronedarone (Sanofi-Synthélabo).

PubMed

Le Grand, B

2001-05-01

Sanofi-Synthelabo (formerly Sanofi) is developing the class III antiarrhythmic agent, dronedarone, for the potential treatment of atrial fibrillation and ventricular tachycardia [157842]. Phase III trials for the treatment of arrhythmia are planned for 2001 [399945]. By December 1998, phase IIb trials for the treatment of cardiac arrhythmia had been initiated [295681,320585], and the compound was shown to have the same efficacy as, and better tolerability than amiodarone [330073]. By 1997, the compound had entered phase IIa trials in Europe [219077,295681]. In November 1997, Sanofi expected to file for marketing in 2001/2 [270242]. ABN Amro predicted sales of FFR 50 million in 2001, rising to FFR 150 million in 2002 [317536]. Lehman Brothers predicted a 20% chance of the compound reaching market, with a launch anticipated in 2003 and potential peak sales of $200 million in 2011 [346267].

Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.

PubMed

Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A; Ganey, Patricia E

2013-01-01

Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity.

Tumor Necrosis Factor-alpha Potentiates the Cytotoxicity of Amiodarone in Hepa1c1c7 Cells: Roles of Caspase Activation and Oxidative Stress

PubMed Central

Ganey, Patricia E.

2013-01-01

Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity. PMID:23042730

Atrial fibrillation after cardiac surgery.

PubMed

Nair, Suresh G

2010-01-01

Once considered as nothing more than a nuisance after cardiac surgery, the importance of postoperative atrial fibrillation (POAF) has been realized in the last decade, primarily because of the morbidity associated with the condition. Numerous causative factors have been described without any single factor being singled out as the cause of this complication. POAF has been associated with stroke, renal failure and congestive heart failure, although it is difficult to state whether POAF is directly responsible for these complications. Guidelines have been formulated for prevention of POAF. However, very few cardiothoracic centers follow any form of protocol to prevent POAF. Routine use of prophylaxis would subject all patients to the side effects of anti-arrhythmic drugs, while only a minority of the patients do actually develop this problem postoperatively. Withdrawal of beta blockers in the postoperative period has been implicated as one of the major causes of POAF. Amiodarone, calcium channel blockers and a variety of other pharmacological agents have been used for the prevention of POAF. Atrial pacing is a non-pharmacological measure which has gained popularity in the prevention of POAF. There is considerable controversy regarding whether rate control is superior to rhythm control in the treatment of established atrial fibrillation (AF). Amiodarone plays a central role in both rate control and rhythm control in postoperative AF. Newer drugs like dronedarone and ranazoline are likely to come into the market in the coming years.

Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model.

PubMed

Xanthos, Theodoros; Psichalakis, Nikolaos; Russell, David; Papalois, Apostolos; Koutsovasilis, Anastasios; Athanasopoulos, Dimitrios; Gkiokas, Georgios; Chalkias, Athanasios; Iacovidou, Nicoletta

2016-08-01

To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS. Copyright © 2016 Elsevier Inc. All rights reserved.

Antiarrhythmic and proarrhythmic properties of QT-prolonging antianginal drugs.

PubMed

Singh, Bramah N; Wadhani, Nitin

2004-09-01

In recent years there has been a major reorientation of drug therapy for cardiac arrhythmias, its changing role, and above all, a radical change in the class of arrhythmia drugs because of their impact on mortality. The decline in the use of sodium-channel blockers has led to an ex panding use of beta-blockers and simple or complex class III agents for controlling cardiac arrhythmias. Success with these agents in the context of their side effects has spurred the development of compounds with simpler ion-channel blocking properties that have less complex adverse reactions. The resulting so-called pure class III agents, such as dofetilide or ibutilide, were found to have antifibrillatory effects in atrial fibrillation and flutter and in ventricular tachyarrhythmias. Such agents are effective and have diversity, but they have come into therapeutics with a price: the sometimes-fatal torsades de pointes. The drug amiodarone, a complex compound that was synthesized as an antianginal agent, has been an exception in this regard. Its therapeutic use is associated with a negligibly low incidence of torsades de pointes, even though the drug produces significant bradycardia and QT lengthening to 500 to 700 msec. Recent electrophysiologic studies suggest that this paradox is likely due to the differential block of ion channels in endocardium, epicardium, midmyocardial (M) cells, and Purkinje fibers in the ventricular myocardium. There is also clinical evidence suggesting that amiodarone reduces the "torsadogenic" effects of pure class III agents. Ranolazine was also synthesized for the development of antianginal properties that stem from a partial inhibition of fatty acid oxidation; it too has been found to have electrophysioloigic properties. These are somewhat similar to those of amiodarone on ion channels in endocardium, epicardium, M cells, and Purkinje fibers in the ventricular myocardium, but the drug does not prolong the QT interval to the same extent as amiodarone does. Thus, the drug produces modest increases in repolarization as judged by its effects on the action potential duration (APD) without the potential for the development of torsades de pointes. By virtue of its suppressant action on early afterdepolarizations and triggered activity in Purkinje fibers and M cells, the drug appears to have a powerful potential for reducing the torsadogenic proclivity of conventional class III antiarrhythmic compounds. The rationale for the therapeutic niche for amiodarone, and especially in the case of ranolazine, in the prevention of drug-induced torsades de pointes is discussed.

Epididymitis

MedlinePlus

... to treat the infection. Sexually transmitted infections need antibiotics. Your sexual partners should also be treated. You may need pain medicines and anti-inflammatory medicines. If you are taking amiodarone, you may ...

Bexarotene

MedlinePlus

... gets on your skin, wash the area with soap and water immediately and call your doctor.Your ... the following: amiodarone (Cordarone); certain antifungals such as ketoconazole (Nizoral) and itraconazole (Sporanox); cimetidine (Tagamet); clarithromycin (Biaxin); ...

Amiodarone

MedlinePlus

... Kaletra, in Viekira Pak); ledipasvir and sofosbuvir (Harvoni); lithium (Lithobid); loratadine (Claritin); medications for diabetes or seizures; ... rash weight loss or gain restlessness weakness nervousness irritability intolerance to heat or cold thinning hair excessive ...

Drug-induced pulmonary disease

MedlinePlus

... are known to cause lung disease in some people. These include: Antibiotics, such as nitrofurantoin and sulfa drugs Heart medicines, such as amiodarone Chemotherapy drugs such as bleomycin, cyclophosphamide, and methotrexate Street drugs

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

PubMed

Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

2015-01-01

Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Une tachycardie à QRS large mal tolérée chez un nourrisson

PubMed Central

Affangla, Désiré Alain; Leye, Mohamed; Simo, Angèle Wabo; D’Almeida, Franck; Sarr, Thérèse Yandé; Phiri, Adamson; Kane, Adama

2017-01-01

Les tachycardies à QRS large mal tolérées du nourrisson posent le problème de leur diagnostic et de la prise en charge en urgence. Nous rapportons un cas de tachycardie à QRS large chez un nourrisson de 35 jours reçu pour détresse cardio-circulatoire. Le cœur était morphologiquement normal à l’échographie cardiaque Doppler. Un traitement par une dose charge d’Amiodarone n’a pas permis de réduire cette tachycardie. Un retour en rythme sinusal a été obtenu après cardioversion par un défibrillateur externe semi-automatique type Lifeline. Un traitement d’entretien par Amiodarone per os est institué et le patient est en rythme sinusal à 03 mois. PMID:28904685

The effects of sternal intraosseous and intravenous administration of amiodarone in a hypovolemic swine cardiac arrest model.

PubMed

Smith, Samuel; Borgkvist, Bradley; Kist, Teara; Annelin, Jason; Johnson, Don; Long, Robert

2016-01-01

This study compared the effects of amiodarone via sternal intraosseous (SIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to ROSC, concentration maximum (C max ), time to maximum concentration (T max ), and mean concentrations over time in a hypovolemic cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the tibial intraosseous TIO or the IV route. Blood samples were collected over 5 minutes. The plasma concentrations were analyzed using high-performance liquid chromatography tandem mass spectrometry. ROSC, time to ROSC, C max , T max , and mean concentrations over time. A multivariate analyses of variance indicated that there were no significant differences in the SIO and IV groups in ROSC (p = 0.191), time to ROSC (p > 0.05), T max mean 88.1 ± 24.8 seconds versus 49.5 ± 21.8 seconds (p = 0.317), or C max mean 92,700 ± 161,112 ng/mL versus 64,159.8 ± 14,174.8 ng/mL (p = 0.260). A repeated analyses of variance indicated that there were no significant differences between the groups relative to concentrations over time (p > 0.05). The SIO provides rapid and reliable access to administer life-saving medications during cardiac arrest.

The effects of tibial intraosseous versus intravenous amiodarone administration in a hypovolemic cardiac arrest procine model.

PubMed

Hampton, Kathryn; Wang, Eric; Argame, Jerome Ivan; Bateman, Tom; Craig, William; Johnson, Don

2016-01-01

This study compared the effects of amiodarone via tibial intraosseous (TIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to ROSC, maximum drug concentration (Cmax), time to maximum concentration (Tmax), and mean concentrations over time in a hypovolemic cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation (CPR) was initiated. After an additional 2 minute, 300 mg of amiodarone were administered via the TIO or the IV route. Blood samples were collected over 5 minutes. The plasma concentrations were analyzed using high-performance liquid chromatography tandem mass spectrometry. ROSC, time to ROSC, Cmax, Tmax, and mean concentrations over time. A multivariate analysis of variance indicated that there were no significant differences in the TIO and IV groups in ROSC (p = 0.515), time to ROSC (p = 0.300), Cmax (p = 0.291), or Tmax (p = 0.475). The mean Cmax of the TIO group was 56,292 ± 11,504 ng/mL compared to 74,258 ± 11,504 ng/mL for the IV group. The Tmax for TIO and IV groups were 120 ± 25 and 94 ± 25, respectively. A repeated measures analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p > 0.05). The TIO provides rapid and reliable access to administer lifesaving medications during cardiac arrest.

Hyperthyroidism: diagnosis and treatment.

PubMed

Reid, Jeri R; Wheeler, Stephen F

2005-08-15

The proper treatment of hyperthyroidism depends on recognition of the signs and symptoms of the disease and determination of the etiology. The most common cause of hyperthyroidism is Graves' disease. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications. The diagnostic workup begins with a thyroid-stimulating hormone level test. When test results are uncertain, measuring radionuclide uptake helps distinguish among possible causes. When thyroiditis is the cause, symptomatic treatment usually is sufficient because the associated hyperthyroidism is transient. Graves' disease, toxic multinodular goiter, and toxic adenoma can be treated with radioactive iodine, antithyroid drugs, or surgery, but in the United States, radioactive iodine is the treatment of choice in patients without contraindications. Thyroidectomy is an option when other treatments fail or are contraindicated, or when a goiter is causing compressive symptoms. Some new therapies are under investigation. Special treatment consideration must be given to patients who are pregnant or breastfeeding, as well as those with Graves' ophthalmopathy or amiodarone-induced hyperthyroidism. Patients' desires must be considered when deciding on appropriate therapy, and dose monitoring is essential.

Pulmonary hypertension and predominant right heart failure in thyrotoxicosis.

PubMed

Paran, Yael; Nimrod, Adi; Goldin, Yelena; Justo, Dan

2006-05-01

In this report we discuss a patient with predominant right heart failure and pulmonary hypertension, caused by thyrotoxicosis due to Graves disease, which deteriorated to asystole, due to amiodarone administration for rapid atrial fibrillation.

Environmental toxicology and risk assessment of pharmaceuticals from hospital wastewater.

PubMed

Escher, Beate I; Baumgartner, Rebekka; Koller, Mirjam; Treyer, Karin; Lienert, Judit; McArdell, Christa S

2011-01-01

In this paper, we evaluated the ecotoxicological potential of the 100 pharmaceuticals expected to occur in highest quantities in the wastewater of a general hospital and a psychiatric center in Switzerland. We related the toxicity data to predicted concentrations in different wastewater streams to assess the overall risk potential for different scenarios, including conventional biological pretreatment in the hospital and urine source separation. The concentrations in wastewater were estimated with pharmaceutical usage information provided by the hospitals and literature data on human excretion into feces and urine. Environmental concentrations in the effluents of the exposure scenarios were predicted by estimating dilution in sewers and with literature data on elimination during wastewater treatment. Effect assessment was performed using quantitative structure-activity relationships because experimental ecotoxicity data were only available for less than 20% of the 100 pharmaceuticals with expected highest loads. As many pharmaceuticals are acids or bases, a correction for the speciation was implemented in the toxicity prediction model. The lists of Top-100 pharmaceuticals were distinctly different between the two hospital types with only 37 pharmaceuticals overlapping in both datasets. 31 Pharmaceuticals in the general hospital and 42 pharmaceuticals in the psychiatric center had a risk quotient above 0.01 and thus contributed to the mixture risk quotient. However, together they constituted only 14% (hospital) and 30% (psychiatry) of the load of pharmaceuticals. Hence, medical consumption data alone are insufficient predictors of environmental risk. The risk quotients were dominated by amiodarone, ritonavir, clotrimazole, and diclofenac. Only diclofenac is well researched in ecotoxicology, while amiodarone, ritonavir, and clotrimazole have no or very limited experimental fate or toxicity data available. The presented computational analysis thus helps setting priorities for further testing. Separate treatment of hospital wastewater would reduce the pharmaceutical load of wastewater treatment plants, and the risk from the newly identified priority pharmaceuticals. However, because high-risk pharmaceuticals are excreted mainly with feces, urine source separation is not a viable option for reducing the risk potential from hospital wastewater, while a sorption step could be beneficial. Copyright © 2010 Elsevier Ltd. All rights reserved.

Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent.

PubMed

Yang, Zhi-fang; Li, Ci-zhen; Wang, Wei; Chen, Ying-min; Zhang, Ying; Liu, Yuan-mou; Wang, Hong-wei

2011-03-01

To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone. Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells. Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate. Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.

Ledipasvir + sofosbuvir (Harvoni). A therapeutic advance in genotype 1 hepatitis C virus infection, despite uncertainties.

PubMed

2015-12-01

Treatment for chronic hepatitis C depends on the hepatitis C virus (HCV) genotype and the patient's clinical characteristics. A fixed-dose combination of ledipasvir + sofosbuvir has been authorised in the European Union for adults with HCV genotype 1 (HCV-1), HCV-3 or HCV-4 infection. Ledipasvir targets the HCV protein NS5A, while sofosbuvir inhibits the HCV RNA polymerase NS5B. The ledipasvir+ sofosbuvircombination has not been compared directly with other antiviral drugs. No information is available on its ability to prevent hepatic complications, even in patients with cirrhosis. In four trials including over 1800 treatment-naive patients infected with HCV-1, a 12-week course of ledipasvir + sofosbuviryielded a sustained virological response in nearly every case. This is better than that reported with peginterferon alfa-based protocols. In four trials including more than 900 HCV-1-infected patients in whom treatments including peginterferon alfa had failed, a 24-week course of ledipasvir+ sofosbuvir yielded a sustained virological response in nearly every case, which is far better than reported with peginterferon alfa + ribavirin + protease inhibitor combinations, based on indirect comparison. In these trials, a 24-week course of the ledipasvir + sofosbuvir combination was effective in almost all patients with compensated cirrhosis. The same treatment also showed major efficacy in a non-comparative trial in 337 HCV-1-infected patients with decompensated cirrhosis or who had undergone liver transplantation. In mid-2015, very few data are available on the ledipasvir + sofosbuvir combination in HCV-1-infected patients in whom sofosbuvir combination therapy has failed, or in patients with HCV-3 or HCV-4 infection. Comparative data on the adverse effects of the ledipasvir + sofosbuvir combination are mainly based on a double-blind, placebo-controlled trial in 155 patients. Overall, serious adverse effects were infrequent in this and other trials. The main adverse effects appear to be headache, fatigue, sleep disorders, irritability and lipase elevations. Hypertension, muscle disorders and dyspnoea are other plausible adverse effects. Bradycardia and cardiac conduction disorders have been reported with concomitant use of sofosbuvir and amiodarone, an antiarrhythmic drug. In practice, in mid-2015, when drug therapy is warranted for chronic hepatitis C due to HCV genotype 1, the ledipasvir + sofosbuvir combination is a first-choice treatment because of its virological efficacy, despite its poorly documented adverse effects. These important outstanding questions call for rigorous pharmacovigilance on the part of all healthcare professionals. It is too early to recommend the ledipasvir + sofosbuvir combination for patients infected with other HCV genotypes. The exorbitant price imposed by Gilead endangers public healthcare systems and undermines access to high-quality care.

Preventing Postoperative Atrial Fibrillation After Noncardiac Surgery: A Meta-analysis.

PubMed

Oesterle, Adam; Weber, Benjamin; Tung, Roderick; Choudhry, Niteesh K; Singh, Jagmeet P; Upadhyay, Gaurav A

2018-07-01

Although postoperative atrial fibrillation is common after noncardiac surgery, there is a paucity of data regarding prophylaxis. We sought to determine whether pharmacologic prophylaxis reduces the incidence of postoperative atrial fibrillation after noncardiac surgery. We performed an electronic search of Ovid MEDLINE, the Cochrane central register of controlled trials database, and SCOPUS from inception to September 7, 2016 and included prospective randomized studies in which patients in sinus rhythm underwent noncardiac surgery and examined the incidence of postoperative atrial fibrillation as well as secondary safety outcomes. Twenty-one studies including 11,608 patients were included. Types of surgery included vascular surgery (3465 patients), thoracic surgery (2757 patients), general surgery (2292 patients), orthopedic surgery (1756 patients), and other surgery (1338 patients). Beta-blockers (relative risk [RR] 0.32; 95% confidence interval [CI], 0.11-0.87), amiodarone (RR 0.42; 95% CI, 0.26 to 0.67), and statins (RR 0.43; 95% CI, 0.27 to 0.68) reduced postoperative atrial fibrillation compared with placebo or active controls. Calcium channel blockers (RR 0.55; 95% CI, 0.30 to 1.01), digoxin (RR 1.62; 95% CI, 0.95 to 2.76), and magnesium (RR 0.73; 95% CI, 0.23 to 2.33) had no statistically significant effect on postoperative atrial fibrillation incidence. The incidence of adverse events was comparable across agents, except for increased mortality (RR 1.33; 95% CI, 1.03 to 1.37) and bradycardia (RR 2.74; 95% CI, 2.19 to 3.43) in patients receiving beta-blockers. Pharmacologic prophylaxis with amiodarone, beta-blockers, or statins reduces the incidence of postoperative atrial fibrillation after noncardiac surgery. Amiodarone and statins have a relatively low overall risk of short-term adverse events. Copyright © 2018 Elsevier Inc. All rights reserved.

Quality by design (QbD) based development and validation of an HPLC method for amiodarone hydrochloride and its impurities in the drug substance.

PubMed

Karmarkar, S; Yang, X; Garber, R; Szajkovics, A; Koberda, M

2014-11-01

The USP monograph describes an HPLC method for seven impurities in the amiodarone drug substance using a L1 column, 4.6mm×150mm, 5μm packing (PF listed ODS2 GL-Science, Inertsil column) at 30°C with detection at 240nm. The standard contains 0.01mg/mL of amiodarone, and USP specified impurities D and E with a resolution requirement of NLT 3.5 between peaks D and E. Impurities in a 5mg/mL sample are quantitated against the standard. Impurity A peak elutes just before peak D. We observed two problems with the method; the column lot-to-lot variability resulted in unresolved A, D, and E peaks, and peak D in the sample preparation eluted much later than that in the standard solution. Therefore, optimization experiments were conducted on the USP method following the QbD approach with Fusion AE™ software (S-Matrix Corporation). The resulting optimized conditions were within the allowable changes per USP 〈621〉. Lot-to-lot variability was negligible with the Atlantis T3 (Waters Corporation) L1 column. Peak D retention time remained constant from standard to sample. The optimized method was validated in terms of accuracy, precision, linearity, range, LOQ/LOD, specificity, robustness, equivalency to the USP method, and solution stability. The QbD based development helped in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of humerus intraosseous versus intravenous amiodarone administration in a hypovolemic porcine model.

PubMed

Holloway, Cpt Monica M; Jurina, Cpt Shannan L; Orszag, Cpt Joshua D; Bragdon, Lt George R; Green, Lt Rustin D; Garcia-Blanco, Jose C; Benham, Brian E; Adams, Ltc Timothy S; Johnson, Don

2016-01-01

To compare the effects of amiodarone administration by humerus intraosseous (HIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to maximum concentration (Tmax), maximum plasma drug concentration (Cmax), time to ROSC, and mean concentrations over time in a hypovolemic cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the HIO or the IV route. Blood samples were collected over 5 minutes. The samples were analyzed using high-performance liquid chromatography tandem mass spectrometry. ROSC, Tmax, Cmax, time to ROSC, and mean concentrations over time. There was no difference in ROSC between the HIO and IV groups; each had five achieve ROSC and two that did not (p = 1). There was no difference in Tmax (p = 0.501) or in Cmax between HIO and IV groups (p = 0.232). Means ± standard deviations in seconds were 94.3 ± 78.3 compared to 115.7 ± 87.3 in the IV versus HIO groups, respectively. The mean ± standard deviation in nanograms per milliliter for the HIO was 49,041 ± 21,107 and 74,258 ± 33,176 for the IV group. There were no significant differences between the HIO and IV groups relative to time to ROSC (p = 0.220). A repeated analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p > 0.05). The humerus intraosseous provides rapid and reliable access to administer life-saving medications during cardiac arrest.

Single jugular vein cannulated rats may not be suitable for intravenous pharmacokinetic screening of high logP compounds.

PubMed

Gaud, Nilesh; Kumar, Anoop; Matta, Muralikrishna; Kole, Prashant; Sridhar, Srikanth; Mandlekar, Sandhya; Holenarsipur, Vinay K

2017-03-01

Rat is commonly used for pharmacokinetic screening during pharmaceutical lead optimization. To handle the large number of compounds, rats with a single jugular vein cannulation are commonly utilized for intravenous pharmacokinetic studies, where the same cannula is used both for dose administration and blood sampling. We demonstrate that the single cannula method is not suitable for all compounds, especially for high logP compounds. We propose an alternative dual cannulation technique in which two cannulas are placed in the same jugular vein, thus avoiding an additional surgery. Compounds were administered orally or via intravenous infusion to compare PK parameters, including bioavailability, using both procedures. For itraconazole and amiodarone, known to bind to the cannula, the measured plasma exposures were substantially higher in the single cannulated rats than those from dual cannulated rats. Area under the plasma concentration time curve differed by 79% and 74% for itraconazole and amiodarone, respectively. When compared to the single cannulation approach, clearance, volume of distribution and bioavailability determined by dual cannulation were 39%, 60% and 38% higher for itraconazole, and 46%, 34% and 42% higher for amiodarone, respectively. In contrast, all pharmacokinetic parameters were similar between single and dual-cannulated rats for the hydrophilic compound atenolol. Based on these results, we recommend the use of dual cannulated rats for intravenous pharmacokinetic studies when testing a series of hydrophobic compounds that may be prone to non-specific binding to the cannula. If single cannulated model is selected for pharmacokinetic screening, we recommend a bridging study with dual cannulated rats with representative compounds of a given chemical series. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of unstable arrhythmias in cardiogenic shock.

PubMed

Saidi, Abdulfattah; Akoum, Nazem; Bader, Feras

2011-08-01

Atrial and ventricular arrhythmias commonly arise in the setting of cardiogenic shock and often result in hemodynamic deterioration. Causative factors include myocardial ischemia, volume overload, and metabolic disturbances. Correcting these factors plays an important role in managing arrhythmias in this setting. Ventricular arrhythmias are more ominous compared to atrial arrhythmias but both require prompt intervention with electrical shock and anti-arrhythmic drug suppression. Coronary reperfusion is key to improving survival, including reducing the risk of sudden cardiac arrest, in acute myocardial infarction. Case series have also demonstrated the value of intra-aortic balloon pump counter-pulsation in suppressing ventricular arrhythmias in cardiogenic shock. The mechanism of arrhythmia suppression may be due to improved coronary perfusion and afterload reduction. Percutaneous ventricular assist device placement may be effective in this setting; however, data addressing this specific endpoint are lacking. Anti-arrhythmic drug options for ventricular and atrial arrhythmia suppression, in the setting of cardiogenic shock, are relatively limited. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone. The other Class III agents, sotalol and dronedarone, are excluded due to associated mortality observed in the SWORD and ANDROMEDA trials, respectively. Dofetilide is renally excreted and causes QT interval prolongation. Care should be taken to avoid excessive drug accumulation due to poor kidney perfusion and function. Dofetilide is approved for use for atrial arrhythmias and has not been studied for ventricular arrhythmia suppression. The DIAMOND-CHF trial established its safety in the setting of heart failure. Amiodarone is very effective in suppressing both atrial and ventricular arrhythmias. It is often the drug of choice in heart failure. Its off-label use for atrial arrhythmias is very common. Care should be taken with intravenous amiodarone to avoid hypotension.

Phenotypic and biomarker evaluation of zebrafish larvae as an alternative model to predict mammalian hepatotoxicity.

PubMed

Verstraelen, Sandra; Peers, Bernard; Maho, Walid; Hollanders, Karen; Remy, Sylvie; Berckmans, Pascale; Covaci, Adrian; Witters, Hilda

2016-09-01

Zebrafish phenotypic assays have shown promise to assess human hepatotoxicity, though scoring of liver morphology remains subjective and difficult to standardize. Liver toxicity in zebrafish larvae at 5 days was assessed using gene expression as the biomarker approach, complementary to phenotypic analysis and analytical data on compound uptake. This approach aimed to contribute to improved hepatotoxicity prediction, with the goal of identifying biomarker(s) as a step towards the development of transgenic models for prioritization. Morphological effects of hepatotoxic compounds (acetaminophen, amiodarone, coumarin, methapyrilene and myclobutanil) and saccharin as the negative control were assessed after exposure in zebrafish larvae. The hepatotoxic compounds induced the expected zebrafish liver degeneration or changes in size, whereas saccharin did not have any phenotypic adverse effect. Analytical methods based on liquid chromatography-mass spectrometry were optimized to measure stability of selected compounds in exposure medium and internal concentration in larvae. All compounds were stable, except amiodarone for which precipitation was observed. There was a wide variation between the levels of compound in the zebrafish larvae with a higher uptake of amiodarone, methapyrilene and myclobutanil. Detection of hepatocyte markers (CP, CYP3A65, GC and TF) was accomplished by in situ hybridization of larvae to coumarin and myclobutanil and confirmed by real-time reverse transcription-quantitative polymerase chain reaction. Experiments showed decreased expression of all markers. Next, other liver-specific biomarkers (i.e. FABP10a and NR1H4) and apoptosis (i.e. CASP-3 A and TP53) or cytochrome P450-related (CYP2K19) and oxidoreductase activity-related (ZGC163022) genes, were screened. Links between basic mechanisms of liver injury and results of biomarker responses are described. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

PubMed

Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J; Rodríguez, Luis A García

2018-03-01

 To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels.  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 ( N  = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t -test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3).  Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%).  Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users. Schattauer GmbH Stuttgart.

Rare acute kidney injury secondary to hypothyroidism-induced rhabdomyolysis.

PubMed

Cai, Ying; Tang, Lin

2013-01-01

Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients. We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism- induced rhabdomyolysis from January 2006 to December 2010. Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification. Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.

Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-β.

PubMed

Cruz, Jader Santos; Machado, Fabiana Simão; Ropert, Catherine; Roman-Campos, Danilo

2017-02-01

Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-β) although other cytokines may be involved in the chagasic cardiomyopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Population modelling to describe pharmacokinetics of amiodarone in rats: relevance of plasma protein and tissue depot binding.

PubMed

Campos Moreno, Eduardo; Merino Sanjuán, Matilde; Merino, Virginia; Nácher, Amparo; Martín Algarra, Rafael V; Casabó, Vicente G

2007-02-01

The objective of this paper was to characterize the disposition phase of AM in rats, after different high doses and modalities of i.v. administration. Three fitting programs, WINNONLIN, ADAPT II and NONMEM were employed. The two-stage fitting methods led to different results, none of which can adequately explain amiodarone's behaviour, although a great amount of data per subject is available. The non-linear mixed effect modelling approach allows satisfactory estimation of population pharmacokinetic parameters, and their respective variability. The best model to define the AM pharmacokinetic profile is a two-compartment model, with saturable and dynamic plasma protein binding and linear tissular depot dynamic binding. These results indicate that peripheral tissues act as depots, causing an important fall in AM plasma levels in the first moment after dosing. Later, the return of the drug from these depots causes a slow increase in serum concentration whenever the dose is reduced.

Double simultaneous defibrillators for refractory ventricular fibrillation.

PubMed

Leacock, Benjamin W

2014-04-01

Out-of-hospital cardiac arrest is a leading cause of death in the United States. Ventricular fibrillation (VF) is the most common initial rhythm after cardiac arrest. To describe a novel approach to the patient with intractable VF after cardiac arrest. A 51-year old man presented in cardiac arrest after a ST-elevation myocardial infarction. He remained in VF despite receiving typical therapy including cardiopulmonary resuscitation, amiodarone, lidocaine, epinephrine, and five attempts at defibrillation with 200 J using a biphasic defibrillator. VF was eventually terminated with 400 J by the simultaneous use of two biphasic defibrillators. The patient had a full recovery. We present a case and supportive literature for a novel treatment of high-energy defibrillation in a patient with refractory VF. Copyright © 2014 Elsevier Inc. All rights reserved.

[Thyroid gland and the heart : Pathophysiological background, diagnostic and therapeutic consequences].

PubMed

Dischinger, U; Fassnacht, M

2018-05-23

Irregularities in thyroid-specific laboratory parameters are frequent in the general population. Observational studies have shown associations between dysfunction of the thyroid gland and cardiovascular morbidity and mortality. The aim of this review is to give a critical overview of the relationship and treatment recommendations for the simultaneous occurrence of functional disorders of the thyroid gland and the heart. Literature searches were conducted in PubMed and Medline. Overt and also to a lesser extent subclinical hyperthyroidism are of relevance for cardiovascular mortality and morbidity, even though interventional studies are missing. Therefore, basic thyroid diagnostics are recommended when cardiovascular diseases occur or deteriorate. Whereas overt hyperthyroidism and hypothyroidism are treated immediately, subclinical thyroid dysfunction disorders require confirmation by laboratory testing. In cases with confirmed subclinical hyperthyroidism and heart disease, a thyroid-specific treatment is meaningful (e. g. with radioiodine). At what point a subclinical hypothyroidism should be treated is controversial. We usually initiate substitution treatment with levothyroxine only in patients with a thyroid-stimulating hormone (TSH) level > 10 mIU/l. A control of baseline thyroid parameters is necessary prior to initiation of any treatment with amiodarone or with deterioration of the general condition.

Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

PubMed

O'Sullivan, Mara; Martinez, Andre; Long, Audrey; Johnson, Michelle; Blouin, Dawn; Johnson, Arthur D; Burgert, James M

2016-01-01

Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

Assessment of the clinical cardiac drug-drug interaction associated with the combination of hepatitis C virus nucleotide inhibitors and amiodarone in guinea pigs and rhesus monkeys.

PubMed

Regan, Christopher P; Morissette, Pierre; Regan, Hillary K; Travis, Jeffery J; Gerenser, Pamela; Wen, Jianzhong; Fitzgerald, Kevin; Gruver, Shaun; DeGeorge, Joseph J; Sannajust, Frederick J

2016-11-01

In 2015, European and U.S. health agencies issued warning letters in response to 9 reported clinical cases of severe bradycardia/bradyarrhythmia in hepatitis C virus (HCV)-infected patients treated with sofosbuvir (SOF) in combination with other direct acting antivirals (DAAs) and the antiarrhythmic drug, amiodarone (AMIO). We utilized preclinical in vivo models to better understand this cardiac effect, the potential pharmacological mechanism(s), and to identify a clinically translatable model to assess the drug-drug interaction (DDI) cardiac risk of current and future HCV inhibitors. An anesthetized guinea pig model was used to elicit a SOF+AMIO-dependent bradycardia. Detailed cardiac electrophysiological studies in this species revealed SOF+AMIO-dependent selective nodal dysfunction, with initial, larger effects on the sinoatrial node. Further studies in conscious, rhesus monkeys revealed an emergent bradycardia and bradyarrhythmia in 3 of 4 monkeys administered SOF+AMIO, effects not observed with either agent alone. Morever, bradycardia and bradyarrhythmia were not observed in rhesus monkeys when intravenous infusion of MK-3682 was completed after AMIO pretreatment. These are the first preclinical in vivo experiments reported to replicate the severe clinical SOF+AMIO cardiac DDI and provide potential in vivo mechanism of action. As such, these data provide a preclinical risk assessment paradigm, including a clinically relevant nonhuman primate model, with which to better understand cardiovascular DDI risk for this therapeutic class. Furthermore, these studies suggest that not all HCV DAAs and, in particular, not all HCV nonstructural protein 5B inhibitors may exhibit this cardiac DDI with amiodarone. Given the selective in vivo cardiac electrophysiological effect, these data enable targeted cellular/molecular mechanistic studies to more precisely identify cell types, receptors, and/or ion channels responsible for the clinical DDI. (Hepatology 2016;64:1430-1441). © 2016 by the American Association for the Study of Liver Diseases.

Evaluation of the effects of PM101, a cyclodextrin-based formulation of intravenous amiodarone, on blood pressure in healthy humans.

PubMed

Cushing, Daniel J; Adams, Michael P; Cooper, Warren D; Zhang, Bing; Lipicky, Raymond J; Kowey, Peter R

2009-10-15

Intravenous amiodarone (AIV) is used to treat cardiac arrhythmias. Hypotension is the dose-limiting adverse event of AIV and is considered to be due to the cosolvents (polysorbate 80 and benzyl alcohol) in the formulation. To minimize hypotension, the initial loading dose of AIV (150 mg) is diluted to 1.5 mg/ml and slowly infused over 10 minutes. PM101 is a cosolvent-free intravenous formulation of amiodarone. The present study was designed to assess any potential hypotensive effect of PM101 (50 mg/ml) on the administration of the loading dose (150 mg) as an undiluted bolus push. This was a randomized, double-blind, placebo- and active-controlled study in healthy human subjects receiving placebo (5% dextrose in water, n = 112) or PM101 (bolus push, n = 112). The primary end point was the noninferiority assessment of placebo versus PM101 for change in systolic blood pressure. For comparison, the standard loading dose of AIV (150 mg) was infused at 1.5 mg/ml over 10 minutes, and a rapid loading dose of AIV (150 mg) was infused undiluted (50 mg/ml) over 15 seconds. PM101 was noninferior to placebo, with changes from baseline systolic blood pressure for placebo and PM101 of -4.25 +/- 4.2 and -4.83 +/- 5.0 mm Hg, respectively. Neither regimen of AIV altered systolic blood pressure compared to placebo. Transient and significant increases in heart rate were observed in both AIV groups and with PM101 but not placebo. In conclusion, the results of this study demonstrate that PM101 is devoid of hypotension in healthy human subjects. The absence of a hypotensive effect of AIV in this population suggests that further evaluation is needed in a patient population with cardiac disease.

[Thyrotoxicosis in heart recipients].

PubMed

Skirzyńska, Dorota; Garlicki, Mirosław; Plicner, Dariusz; Wysocka, Teresa; Wierzbicki, Karol; Biernat, Marta; Sadowski, Jerzy

2002-01-01

Between 1992 and 2000 in the group of the patients before heart transplantation, amiodarone induced thyrotoxicosis occurred in 5 (4 male and 1 female, average age 45.5 years) patients. In four of the patients of that group orthotopic heart transplantation was done. Postoperative period in the patients with euthyreosis was uncomplicated. One patient died after HTx because of thyroid crisis.

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging.

PubMed

Dempsey, Graham T; Chaudhary, Khuram W; Atwater, Nicholas; Nguyen, Cuong; Brown, Barry S; McNeish, John D; Cohen, Adam E; Kralj, Joel M

2016-01-01

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative seeks an in vitro test to accurately predict clinical Torsades de Pointes (TdP). We developed a cardiotoxicity assay incorporating simultaneous measurement of the action potential (AP) waveform and Ca(2+) transient (CT) in human iPSC-derived cardiomyocytes (CMs). Concurrent optogenetic pacing provided a well-controlled electrophysiological background. We used the Optopatch platform for all-optical electrophysiology (Hochbaum et al., 2014). In a monolayer culture, a subset of cells expressed a genetically encoded, calcium and voltage reporter, CaViar (Hou, Kralj, Douglass, Engert, & Cohen, 2014), while others expressed a channelrhodopsin variant, CheRiff. Optical pacing of CheRiff-expressing cells synchronized the syncytium. We screened 12 compounds (11 acute, 1 chronic) to identify electrophysiological (AP rise time, AP50, AP90, beat rate) and CT effects in spontaneously beating and paced cultures (1Hz, 2Hz). CaViar reported spontaneous and paced APs and CTs with high signal-to-noise ratio and low phototoxicity. Quinidine, flecainide, E-4031, digoxin and cisapride prolonged APs, while verapamil and nifedipine shortened APs. Early after depolarizations (EADs) were elicited by quinidine, flecainide and cisapride. All but four compounds (amiodarone, chromanol, nifedipine, verapamil) prolonged AP rise time. Nifedipine and verapamil decreased CT amplitude, while digoxin increased CT amplitude. Pentamidine prolonged APs after chronic exposure. The Optopatch platform provides a robust assay to measure APs and CTs in hiPSC-CMs. This addresses the CiPA mandate and will facilitate comparisons of cell-based assays to human clinical data. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical management of hyperthyroidism.

PubMed

Quérat, C; Germain, N; Dumollard, J-M; Estour, B; Peoc'h, M; Prades, J-M

2015-04-01

Hyperthyroidism includes several clinical and histopathological situations. Surgery is commonly indicated after failure of medical treatment. The aim of this study was to analyze the indications and complications of surgery as well as endocrine results. Patients operated on for hyperthyroidism between 2004 and 2012 were included in a retrospective study. Total thyroidectomy was performed for Graves' disease, toxic multinodular goiter and amiodarone-associated thyrotoxicosis; patients with toxic nodule underwent hemithyroidectomy. Pathologic analysis assessed surgical specimens; postoperative complications and resolution of hyperthyroidism were noted. Two hundred patients from 15 to 83 years old were included. One hundred and eighty-eight underwent primary surgery and 12 were re-operated for recurrent goiter (6 with subtotal thyroidectomy for multinodular goiter 25 years previously; 6 with hemithyroidectomy for solitary nodule 15 years previously). Eighty-two patients suffered from toxic multinodular goiter, 78 from Graves' disease, 35 from solitary toxic nodules and 5 from amiodarone-associated thyrotoxicosis. Fourteen papillary carcinomas (including 11 papillary microcarcinomas) and 34 healthy parathyroid glands (17%) were identified in the pathological specimens. Postoperative complications comprised 4% permanent recurrent laryngeal nerve palsy (1 year follow-up), 9% hematoma requiring surgical revision, and 3% definitive hypocalcemia. Normalization of thyroid hormone levels was observed in 198 patients. Two recurrences occurred due to incomplete resection (1 case of Graves' disease and 1 intrathoracic toxic goiter that occurred respectively 18 and 5 months after resection). Postoperative complications were more frequent in multinodular goiter (23%) than in Graves' disease (13%) (ns: P>0.05). Surgical management of hyperthyroidism enables good endocrinal control if surgery is complete. Patients need to be fully informed of all possible postoperative complications that could occur, especially vocal ones. Long-term follow-up is necessary to detect recurrence, which can occur more than 20 years after partial thyroidectomy surgery. Surgery allows early diagnosis of 12.5% of papillary carcinomas. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

PubMed Central

Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

2016-01-01

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF. PMID:27984585

Survival of a highly toxic dose of caffeine.

PubMed

Bioh, Gabriel; Gallagher, Mark M; Prasad, Usha

2013-02-08

A 27-year-old woman with a history of depression and previous overdose presented within 60 min of ingestion of 50 g of caffeine powder. Initially alert but hypotensive and tachycardic, the patient developed a broad complex tachycardia followed by a seizure and multiple ventricular fibrillation (VF) arrests. Following multiple defibrillations for VF, eight cycles of cardiopulmonary resuscitation and treatment with amiodarone, lidocaine, magnesium and potassium supplementation, the patient went to the intensive care unit (ICU). While there, the patient had further VF and required haemofiltration for a profound metabolic acidaemia with cardiac rhythm instability. She developed a postcardiac arrest systemic inflammatory response syndrome with episodes of acute pulmonary oedema, profound vasoplegia, hypothermia and coagulopathy. After 5 days in the ICU, the patient was stable enough to be transferred to the ward, with a persistent sinus tachycardia, and was discharged 3 days later with cardiology and psychiatry follow-up.

Drug safety evaluation of dronedarone in atrial fibrillation.

PubMed

De Ferrari, Gaetano M; Dusi, Veronica

2012-11-01

Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.

The Impact of the Hepatocyte-to-Plasma pH Gradient on the Prediction of Hepatic Clearance and Drug-Drug Interactions for CYP2C9 and CYP3A4 Substrates.

PubMed

Rougée, Luc R A; Mohutsky, Michael A; Bedwell, David W; Ruterbories, Kenneth J; Hall, Stephen D

2017-09-01

Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH is 7.0. This pH gradient can result in a pK a -dependent change in intracellular/extracellular concentrations for ionizable drugs that could affect predictions of clearance and P450 inhibition. The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated. Intrinsic clearance through CYP2C9 significantly increased (25% and 50% for diclofenac and (S)-warfarin respectively) at intracellular pH 7.0 compared with traditional pH 7.4. The CYP3A4 substrate dextromethorphan intrinsic clearance was decreased by 320% at pH 7.0, while midazolam and testosterone remained unchanged. Reversible inhibition of CYP2C9 was less potent at pH 7.0 compared with 7.4, while CYP3A4 inhibition potency was variably affected. Maximum enzyme inactivation rate of amiodarone toward CYP2C9 and CYP3A4 decreased at pH 7.0, while the irreversible inhibition constant remained unchanged for CYP2C9, but decreased for CYP3A4 at pH 7.0. Predictions of clearance and drug-drug interactions made through physiologically based pharmacokinetic models were improved with the inclusion of predicted intracellular concentrations based at pH 7.0 and in vitro parameters determined at pH 7.0. No general conclusion on the impact of pH could be made and therefore a recommendation to change buffer pH to 7.0 cannot be made at this time. It is recommended that the appropriate hepatocyte intracellular pH 7.0 be used for in vitro determinations when in vivo predictions are made. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

New-onset atrial fibrillation: an update.

PubMed

Omae, Takeshi; Inada, Eiichi

2018-06-01

New-onset atrial fibrillation (NOAF) is the most common perioperative complication of heart surgery, typically occurring in the perioperative period. NOAF commonly occurs in patients who are elderly, or have left atrial enlargement, or left ventricular hypertrophy. Various factors have been identified as being involved in the development of NOAF, and numerous approaches have been proposed for its prevention and treatment. Risk factors include diabetes, obesity, and metabolic syndrome. For prevention of NOAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. NOAF can be treated by rhythm/rate control, and antithrombotic therapy. Treatment is required in patients with decreased cardiac function, a heart rate exceeding 130 beats/min, or persistent NOAF lasting for ≥ 48 h. It is anticipated that anticoagulant therapies, as well as hemodynamic management, will also play a major role in the management of NOAF. When using warfarin as an anticoagulant, its dose should be adjusted based on PT-INR. PT-INR should be controlled between 2.0 and 3.0 in patients aged < 70 years and between 1.6 and 2.6 in those aged ≥ 70 years. Rate control combined with antithrombotic therapies for NOAF is expected to contribute to further advances in treatment and improvement of survival.

Hyperthyroidism.

PubMed

Maji, D

2006-10-01

Hyperthyroidism is a clinical situation where there is excess thyroid hormones in the circulation due to increased synthesis of hormone from a hyperactive thyroid gland. Common causes are Graves' disease, toxic multinodular goitre and toxic solitary nodule. Excess thyroid hormones in the circulation are also found in thyroiditis (hormone leakage) and excess exogenous thyroxine intake. Thyrotoxicosis is the term applied when there is excess thyroid hormone in the circulation due to any cause. Thyrotoxicosis can be easily diagnosed by high serum level of thyroxine (T4) and triiodothyronine (T3) and low serum level of thyroid stimulating hormone (TSH). Hyperthyroidism is confirmed by high isotope (I 131 or Tc99) uptake by the thyroid gland, while in thyroiditis it will be low. Treatment of hyperthyroidism depends on the underlying cause. Antithyroid drugs, 1131 therapy and surgery are the options of treatment of hyperthyroidism. Surgery is the preferred treatment for toxic adenoma and toxic multinodular goitre, while 1131 therapy may be suitable in some cases. Antithyroid drugs and 1131 therapy are mostly preferred for Graves' disease. Beta-adrenergic blockers are used for symptomatic relief in most patients of thyrotoxicosis due to any cause. Other rare causes of hyperthyroidism like, amiodarone induced thyrotoxicosis, choriocarcinoma, thyrotropin secreting pituitary tumour are difficult to diagnose as well as to treat.

[Atrial fibrillation].

PubMed

Spinar, J; Vítovec, J

2003-09-01

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C.

PubMed

Fazel, Yousef; Lam, Brian; Golabi, Pegah; Younossi, Zobair

2015-08-01

The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy. The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available. In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

Evaluation of genotype-guided acenocoumarol dosing algorithms in Russian patients.

PubMed

Sychev, Dmitriy Alexeyevich; Rozhkov, Aleksandr Vladimirovich; Ananichuk, Anna Viktorovna; Kazakov, Ruslan Evgenyevich

2017-05-24

Acenocoumarol dose is normally determined via step-by-step adjustment process based on International Normalized Ratio (INR) measurements. During this time, the risk of adverse reactions is especially high. Several genotype-based acenocoumarol dosing algorithms have been created to predict ideal doses at the start of anticoagulant therapy. Nine dosing algorithms were selected through a literature search. These were evaluated using a cohort of 63 patients with atrial fibrillation receiving acenocoumarol therapy. None of the existing algorithms could predict the ideal acenocoumarol dose in 50% of Russian patients. The Wolkanin-Bartnik algorithtm based on European population was the best-performing one with the highest correlation values (r=0.397), mean absolute error (MAE) 0.82 (±0.61). EU-PACT also managed to give an estimate within the ideal range in 43% of the cases. The two least accurate results were yielded by the Indian population-based algorithms. Among patients receiving amiodarone, algorithms by Schie and Tong proved to be the most effective with the MAE of 0.48±0.42 mg/day and 0.56±0.31 mg/day, respectively. Patient ethnicity and amiodarone intake are factors that must be considered when building future algorithms. Further research is required to find the perfect dosing formula of acenocoumarol maintenance doses in Russian patients.

Pharmacological conversion of recent-onset atrial fibrillation: a systematic review.

PubMed

Heldal, Magnus; Atar, Dan

2013-02-01

Recent-onset (duration ≤ 1 week) atrial fibrillation (AF) has a high rate of spontaneous conversion to sinus rhythm (SR); still anti-arrhythmic drugs (AAD) are given for conversion purposes. We assessed the effect of AADs by reviewing the literature regarding conversion rates of available drugs in a systematic manner. PubMed searches were performed using the terms "drug name", "atrial fibrillation", and "clinical study/RCT", and a list of 1302 titles was generated. These titles, including abstracts or complete papers when needed, were reviewed for recent-onset of AF, the use of a control group, and the endpoint of SR within 24 hours. Postoperative and intensive care settings were excluded. Five AADs were demonstrated to have an effect, and these were Amiodarone, Ibutilide (only one study and risk of torsade de pointes), Flecainide and Propafenone (only to be used in patients without structural heart disease) and Vernakalant. The time taken for conversion differed markedly; Vernakalant converted after 10 minutes, while Amiodarone converted only after 24 hours; Propafenone and Flecainide had conversion times in-between. For a rapid response in a broad group of patients, Vernakalant appears to be a reasonable first choice, while Flecainide and Propafenone can be used in patients without structural heart disease.

Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis.

PubMed

Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria

2017-12-01

Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p < 0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

The management of ventricular dysrhythmia in aconite poisoning.

PubMed

Coulson, James M; Caparrotta, Thomas M; Thompson, John P

2017-06-01

Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to the presence of an admixture of alkaloids present in all parts of the plant. The major target of these aconite alkaloids is the fast voltage-gates sodium channel, where they cause persistent activation. This blockade of the channel in the activated state promotes automaticity within the ventricular myocardium and the generation of ventricular arrhythmias. Aconitine-induced arrhythmias: Aconite alkaloids are known to cause many different types of disturbance of heart rhythm. However, this focused review specifically looks at ventricular rhythm disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des pointes and ventricular fibrillation. The objective of this review was to identify the outcome of anti-dysrhythmic strategies from animal studies and case reports in humans in order to guide the management of ventricular dysrhythmias in aconite poisoning in humans. A review of the literature in English was conducted in PubMed and Google Scholar from 1966 to July 2016 using the search terms "aconite/aconitine"; "aconite/aconitine + poisoning" and "aconite/aconitine + dysrhythmia". 168 human case-reports and case-series were identified by these searches, of which 103 were rejected if exposure to aconite did not result in ventricular dysrhythmias, if it was uncertain as to whether aconite had been ingested, if other agents were co-ingested, if there was insufficient information to determine the type of treatments administered or if there was insufficient information to determine outcome. Thus, 65 case reports of probable aconite poisoning that resulted in ventricular dysrhythmias were identified. Toxicokinetic data in aconite poisoning: Data were only available in three papers; the presence of ventricular rhythm disturbances directly correlated with the concentration of aconite alkaloids in the plasma. 54 of 65 cases developed ventricular tachycardia, six developed torsades des pointes, 15 patients developed ventricular fibrillation, 10 developed ventricular ectopics and one developed a broad complex tachycardia not otherwise specified; each dysrhythmia was regarded as separate and patients may have had more than one dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147 treatments were administered to 65 patients. 46 of the interventions were assessed by the authors as having been associated with successful restoration of sinus rhythm. Flecainide administration was accompanied by dysrhythmia termination in six of seven cases. Mexiletine was connected with correcting dysrhythmias in 3 of 3 cases. Procainamide administration was associated with return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation was administered to 15 patients where it was associated with a return to sinus rhythm in nine of these. Amiodarone was linked to success in correcting dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a return to sinus rhythm in four out of six cases. Epinephrine was documented as being employed on four occasions, and was associated with a restoration of sinus rhythm on two of these. Magnesium sulphate administration was accompanied by dysrhythmia termination in two of nine cases. Direct cardioversion was associated with a return of sinus rhythm in 5 of 30 cases. However, it is not certain whether the drug treatment influenced the course of the dysrhythmia. Based on the evidence available from human case reports, flecainaide or amiodarone appear to be more associated with a return to sinus rhythm than lidocaine and/or cardioversion, although it is not established whether the administration of treatment caused reversion to normal sinus rhythm. The potential beneficial effects of amiodarone were not observed in animal studies. This may be due to intra-species differences between ion channels or relate to the wider cardiovascular toxicity of aconite that extends beyond arrhythmias. Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be considered as an integral part of good clinical care as "time-buying" strategies to allow the body to excrete the toxic alkaloids. There may also be a role for mexiletine, procainamide and magnesium sulphate.

Does Pharmacological Therapy Still Play a Role in Preventing Sudden Death in Surgically Treated Tetralogy of Fallot?

PubMed

Gabriele, Bronzetti; Maurizio, Brighenti; Marco, Bonvicini

2018-01-01

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, with a familial recurrence risk of 3%. Despite performing an optimal surgical repair, TOF patients may feature a poor medium and long-term survival rate: atrial re-entrant tachycardia will develop in more than 30% of patients and high-grade ventricular arrhythmias will be seen in about 10% of patients. These life-threatening arrhythmias and consequent sudden death continue to represent serious complications following TOF repair. Radiofrequency ablation and implantable cardioverter defibrillator are today the most effective therapeutic tools in these subjects, while the administration of antiarrhythmic drugs (Ib agents, beta blockers, and amiodarone), widely prescribed in the past, is now limited to few conditions. However pharmacological therapy still plays a role in the management of those patients who are resistant to the above stated invasive electrophysiological treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Thyroid storm in a patient with Wolff-Parkinson-White syndrome.

PubMed

Naqvi, Syed Yaseen; Luebbert, Jeffrey J; Rosen, Stephen G

2015-12-15

A 44-year-old woman with no medical history presented to the emergency department with a 2 h history of sudden onset chest pressure, palpitations, diaphoresis and shortness of breath. She reported a 90-pound unintentional weight loss, increased appetite, irritability, night sweats and palpitations for 2 months. Physical examination revealed a heart rate (HR) of 269 bpm and a blood pressure of 116/94 mm Hg. Her ECG revealed a wide-complex tachycardia with right bundle branch morphology and an HR of 265 bpm. Intravenous adenosine was administered with resolution of the arrhythmia and symptoms. Her subsequent ECG revealed sinus tachycardia with δ waves, which was consistent with Wolff-Parkinson-White (WPW) syndrome. Laboratory findings confirmed thyroid storm and treatment began with intravenous hydrocortisone, methimazole, metoprolol, amiodarone and iodine drops. Graves' disease was confirmed based on the presence of serum thyroid-stimulating hormone receptor antibody. The patient underwent successful WPW accessory tract ablation 6 weeks after initial presentation. 2015 BMJ Publishing Group Ltd.

Cardiovascular drugs inducing QT prolongation: facts and evidence.

PubMed

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

2010-01-01

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

Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory support.

PubMed

Potapov, Evgenij V; Dranishnikov, Nikolay; Morawietz, Lars; Stepanenko, Alexander; Rezai, Sajjad; Blechschmidt, Cristiane; Lehmkuhl, Hans B; Weng, Yuguo; Pasic, Miralem; Hübler, Michael; Hetzer, Roland; Krabatsch, Thomas

2012-11-01

Continuous-flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the effect of long-term CF with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (> 3 years), remains unclear. Tissue samples obtained at autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients supported for > 180 days between 2000 and 2010 were histologically examined to assess vascular alterations, including perivascular infiltrate, intravascular infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been inserted in 9 patients and CF devices had been inserted in 16. The pathologist was blinded to the group distribution. Demographic, pharmacologic, and clinical data were retrospectively analyzed before surgery and during the follow-up period of up to 24 months. Median duration of support was 467 days (range, 235-1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group. Demographic and clinical data before and after surgery were similar. Amiodarone was more often used during follow-up in CF group than in the PF group (61% vs 10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not differ between recipients of the 2 pump types, nor did systolic and diastolic pressure, except at 2 weeks after VAD implantation, when systolic blood pressure was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic studies did not identify any relevant differences in arterial wall characteristics between the 2 groups. Long-term mechanical circulatory support with CF devices does not adversely influence arterial wall properties of the end-organ vasculature. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Rescue pulmonary vein isolation for hemodynamically unstable atrial fibrillation storm in a patient with an acute extensive myocardial infarction.

PubMed

Morishima, Itsuro; Sone, Takahito; Tsuboi, Hideyuki; Mukawa, Hiroaki

2012-11-26

New-onset atrial fibrillation in patients hospitalized for an acute myocardial infarction often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular ejection fraction. The mechanism of atrial fibrillation in the context of an acute myocardial infarction has not been well characterized and an effective treatment other than optimal medical therapy and mechanical hemodynamic support are expected. A 71 year-old male with an acute myocardial infarction due to an occlusion of the left main coronary artery was treated with percutaneous coronary intervention. He had developed severe congestive heart failure with a left ventricular ejection fraction of 34%. The systemic circulation was maintained with an intraaortic balloon pump, continuous hemodiafiltration, and mechanical ventilation until atrial fibrillation occurred on day 3 which immediately led to cardiogenic shock. Because atrial fibrillation was refractory to intravenous amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent emergent radiofrequency catheter ablation on day 4. Soon after electrical cardioversion, ectopies from the right superior pulmonary vein triggered the initiation of atrial fibrillation. The right pulmonary veins were isolated during atrial fibrillation. Again, atrial fibrillation was electrically cardioverted, then, sinus rhythm was restored. Subsequently, the left pulmonary veins were isolated. The stabilization of the hemodynamics was successfully achieved with an increase in the blood pressure and urine volume. Hemodiafiltration and amiodarone were discontinued. The patient had been free from atrial fibrillation recurrence until he suddenly died due to ventricular fibrillation on day 9. To the best of our knowledge, this is the first report of pulmonary vein isolation for a rescue purpose applied in a patient with hemodymically unstable atrial fibrillation complicated with an acute myocardial infarction. This case demonstrates that ectopic activity in the pulmonary veins may be responsible for triggering atrial fibrillation in the critical setting of an acute myocardial infarction and thus pulmonary vein isolation could be an effective therapeutic option.

Delayed Onset of Atrial Fibrillation and Ventricular Tachycardia after an Automobile Lightning Strike.

PubMed

Drigalla, Dorian; Essler, Shannon E; Stone, C Keith

2017-11-01

Lightning strike is a rare medical emergency. The primary cause of death in lightning strike victims is immediate cardiac arrest. The mortality rate from lightning exposure can be as high as 30%, with up to 70% of patients left with significant morbidity. An 86-year-old male was struck by lightning while driving his vehicle and crashed. On initial emergency medical services evaluation, he was asymptomatic with normal vital signs. During his transport, he lost consciousness several times and was found to be in atrial fibrillation with intermittent runs of ventricular tachycardia during the unconscious periods. In the emergency department, atrial fibrillation persisted and he experienced additional episodes of ventricular tachycardia. He was treated with i.v. amiodarone and admitted to cardiovascular intensive care unit, where he converted to a normal sinus rhythm on the amiodarone drip. He was discharged home without rhythm-control medications and did not have further episodes of dysrhythmias on follow-up visits. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Lightning strikes are one of the most common injuries suffered from natural phenomenon, and short-term mortality ordinarily depends on the cardiac effects. This case demonstrates that the cardiac effects can be multiple, delayed, and recurrent, which compels the emergency physician to be vigilant in the initial evaluation and ongoing observation of patients with lightning injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

PubMed

Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

2017-09-01

Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using statistical anomaly detection models to find clinical decision support malfunctions.

PubMed

Ray, Soumi; McEvoy, Dustin S; Aaron, Skye; Hickman, Thu-Trang; Wright, Adam

2018-05-11

Malfunctions in Clinical Decision Support (CDS) systems occur due to a multitude of reasons, and often go unnoticed, leading to potentially poor outcomes. Our goal was to identify malfunctions within CDS systems. We evaluated 6 anomaly detection models: (1) Poisson Changepoint Model, (2) Autoregressive Integrated Moving Average (ARIMA) Model, (3) Hierarchical Divisive Changepoint (HDC) Model, (4) Bayesian Changepoint Model, (5) Seasonal Hybrid Extreme Studentized Deviate (SHESD) Model, and (6) E-Divisive with Median (EDM) Model and characterized their ability to find known anomalies. We analyzed 4 CDS alerts with known malfunctions from the Longitudinal Medical Record (LMR) and Epic® (Epic Systems Corporation, Madison, WI, USA) at Brigham and Women's Hospital, Boston, MA. The 4 rules recommend lead testing in children, aspirin therapy in patients with coronary artery disease, pneumococcal vaccination in immunocompromised adults and thyroid testing in patients taking amiodarone. Poisson changepoint, ARIMA, HDC, Bayesian changepoint and the SHESD model were able to detect anomalies in an alert for lead screening in children and in an alert for pneumococcal conjugate vaccine in immunocompromised adults. EDM was able to detect anomalies in an alert for monitoring thyroid function in patients on amiodarone. Malfunctions/anomalies occur frequently in CDS alert systems. It is important to be able to detect such anomalies promptly. Anomaly detection models are useful tools to aid such detections.

Drug-induced corneal damage.

PubMed

2014-04-01

Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.

Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components.

PubMed

Stoykov, I; van Beeren, H C; Moorman, A F M; Christoffels, V M; Wiersinga, W M; Bakker, O

2007-06-01

In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. Rats were treated with AM or Dron and the expression of TRalpha 1, TRalpha 2, TRbeta 1 and several tri-iodothyronine (T3)-regulated genes was studied in different parts of the heart, namely the right atrium (RA), left ventricular wall (LVW) and apex. Rats were treated for 14 days with 100 mg/kg body weight AM or Dron. The expression of TRalpha 1, TRalpha 2, TRbeta 1 and T3-regulated genes was studied using real-time PCR and non-radioactive in situ hybridisation. AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%. In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1. In the apex, AM also increased TRalpha 2. The changes seen in T3-dependent gene expression are reminiscent of foetal reprogramming. Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.

Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.

PubMed

Van Beeren, H C; Jong, W M C; Kaptein, E; Visser, T J; Bakker, O; Wiersinga, W M

2003-02-01

Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we investigate whether Dron and/or its metabolite debutyldronedarone inhibit T(3) binding to TRalpha(1) and TRbeta(1) in vitro and whether dronedarone behaves similarly to amiodarone in vivo. In vitro, Dron had a inhibitory effect of 14% on the binding of T(3) to TRalpha(1), but not on TRbeta(1). Desethylamiodarone inhibited T(3) binding to TRalpha(1) and TRbeta(1) equally. Debutyldronedarone inhibited T(3) binding to TRalpha(1) by 77%, but to TRbeta(1) by only 25%. In vivo, AM increased plasma TSH and rT(3), and decreased T(3). Dron decreased T(4) and T(3), rT(3) did not change, and TSH fell slightly. Plasma total cholesterol was increased by AM, but remained unchanged in Dron-treated animals. TRbeta(1)-dependent liver low density lipoprotein receptor protein and type 1 deiodinase activities decreased in AM-treated, but not in Dron-treated, animals. TRalpha(1)-mediated lengthening of the QTc interval was present in both AM- and Dron-treated animals. The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.

The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone.

PubMed

Joukar, Siyavash; Dehesh, Mohammad-Moein

2015-12-01

Dry stigmas of the Crocus sativus L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart. This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat. Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated. The heart rate decreased and RR interval increased in Saf200 and Amio groups (P<.05 vs other groups). Square root of the mean squared differences of successive RR intervals enhanced in all treated groups, however, was only significant in Amio group (P<.05). The SD1/SD2 ratio was higher in Saf200 and Amio groups. Both low-frequency (LF) and high-frequency (HF) parameters were higher, and the LF/HF ratio was non-significantly lower in treated groups. The findings suggest that saffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat. © 2016 John Wiley & Sons Ltd.

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

PubMed

Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

2016-09-28

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

PubMed

Sorrentino, Annalise

2005-04-01

Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats.

PubMed

Valcheva-Kuzmanova, Stefka; Stavreva, Galya; Dancheva, Violeta; Terziev, Ljudmil; Atanasova, Milena; Stoyanova, Angelina; Dimitrova, Anelia; Shopova, Veneta

2014-04-01

The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when biochemical, cytological, and immunological assays were performed. AMFJ antagonized AD-induced increase of the lung weight coefficient. In bronchoalveolar lavage fluid, AD increased significantly the protein content, total cell count, polymorphonuclear cells, lymphocytes and the activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not differ significantly from the control values. In lung tissue, AD induced oxidative stress measured by malondialdehyde content and fibrosis assessed by the hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL-10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that did not differ significantly from the control ones. AMFJ could have a protective effect against AD-induced pulmonary toxicity as evidenced by the reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation, and fibrosis.

Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

NASA Astrophysics Data System (ADS)

Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean

2016-02-01

Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P < 0.001). The PPX[AMIO, DEX] group was similar to native PPX (PPX 0.38 +/- 0.48 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P&z.dbd;NS). PPX-Oxd group adhesions were indistinguishable from controls (PPX-Oxd 2.83 +/- 0.41 vs. control 2.75 +/- 0.42, P&z.dbd;NS). NTF was reduced in the PPX[AMIO, DEX] group (0.80 +/- 0.10 mm) compared to control (1.78 +/- 0.13 mm, P < 0.001). Total duration of atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P < 0.001). The PPX[AMIO, DEX] group was similar to native PPX (PPX 0.38 +/- 0.48 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P&z.dbd;NS). PPX-Oxd group adhesions were indistinguishable from controls (PPX-Oxd 2.83 +/- 0.41 vs. control 2.75 +/- 0.42, P&z.dbd;NS). NTF was reduced in the PPX[AMIO, DEX] group (0.80 +/- 0.10 mm) compared to control (1.78 +/- 0.13 mm, P < 0.001). Total duration of atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07456h

Sotalol: An important new antiarrhythmic.

PubMed

Anderson, J L; Prystowsky, E N

1999-03-01

Sotalol, the most recently approved oral antiarrhythmic drug, has a unique pharmacologic profile. Its electrophysiology is explained by nonselective beta-blocking action as well as class III antiarrhythmic activity (including fast-activating cardiac membrane-delayed rectifier current blockade), which leads to increases in action potential duration and refractory period throughout the heart and in QT interval on the surface electrocardiogram. Its better hemodynamic tolerance than other beta-blockers may be a result of enhanced inotropy associated with class III activity. Sotalol's ability to suppress ventricular ectopy is similar to that of class I agents and better than that of standard beta-blockers. Unlike class I agents, its use in a postinfarction trial was not associated with increased mortality rate. Therapeutically, it has shown superior efficacy for prevention of recurrent ventricular tachycardia and ventricular fibrillation, which was the basis for its approval. In a randomized study, the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, sotalol was associated with an increased in-hospital efficacy prediction rate (by Holter monitor or electrophysiologic study), reduced long-term arrhythmic recurrence rate with superior tolerance, and lower mortality rate than class I ("standard") antiarrhythmic drugs. Sotalol was 1 of 2 drugs selected for comparison with implantable defibrillators in the recent National Institutes of Health Antiarrhythmics versus Implantable Defibrillator (AVID) study. Sotalol appears to be a preferred drug for use with implantable defibrillators; unlike some other agents (eg, amiodarone) it does not elevate and, indeed, may lower defibrillation threshold. Although unapproved for this use, sotalol is active against atrial arrhythmias. It has shown efficacy equivalent to propafenone and quinidine in preventing atrial fibrillation recurrence, but it is better tolerated than quinidine and provides excellent rate control during recurrence. Sotalol's major side effects are related to beta-blockade and the risk of torsades de pointes (acceptably small if appropriate precautions are taken). Unlike several other antiarrhythmics (eg, amiodarone), it has no pharmacokinetic drug-drug interactions, is not metabolized, and is entirely renally excreted. Initial dose is 80 mg twice daily, with gradual titration to 240 to 360 mg/day as needed. The daily dose must be reduced in renal failure. On the basis of favorable clinical trials and practice experience, sotalol has shown a steadily growing impact on the treatment of arrhythmias during its 5 years of market availability, a trend that is likely to continue.

Diagnosis, treatment, and nursing care of patients with chronic leukemia.

PubMed

Breed, Cheryl D

2003-05-01

To provide an update on the impact of new information about the molecular biology of chronic leukemia and new treatment modalities available to patients. Published articles, books, and research studies. There has been significant progress in the diagnosis and management of chronic myeloid and chronic lymphocytic leukemia. New therapies provide more options for patients and longer treatment periods. With increasing treatment options and longer survival, patients with chronic myelogenous or chronic lymphocytic leukemia need increased education, support, and assistance with symptom management. Nurses caring for these patients must remain knowledgeable about new treatments and their management.

Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo; Boyer, Edward; Naqvi, Zafar N; Rosenbaum, Christopher; Ziedonis, Douglas

2011-01-01

Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain. PMID:24474854

Sex differences in the prehospital management of out-of-hospital cardiac arrest.

PubMed

Mumma, Bryn E; Umarov, Temur

2016-08-01

Sex differences exist in the diagnosis and treatment of several cardiovascular diseases. Our objective was to determine whether sex differences exist in the use of guideline-recommended treatments in out-of-hospital cardiac arrest (OHCA). We included adult patients with non-traumatic OHCA treated by emergency medical services (EMS) in the Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) database during 2007-2009. Outcomes included prehospital treatment intervals, procedures, and medications. Data were analysed using multivariable linear and logistic regression models that adjusted for sex, age, witnessed arrest, public location, bystander cardiopulmonary resuscitation (CPR), and first known rhythm of ventricular tachycardia/fibrillation. We studied 15,584 patients; 64% were male and median age was 68 years (interquartile range 55-80). In multivariable analyses, intervals from EMS dispatch to first rhythm capture (p=0.001) and first EMS CPR (p=0.001) were longer in women than in men. Women were less likely to receive successful intravenous or intraosseous access (OR 0.78, 95% CI 0.71-0.86) but equally likely to receive a successful advanced airway (OR 0.94, 95% CI 0.86-1.02). Women were less likely to receive adrenaline (OR 0.81, 95% CI 0.74-0.88), atropine (OR 0.86, 95% CI 0.80-0.92), and lidocaine or amiodarone (OR 0.68, 95% CI 0.61-0.75). Women were less likely than men to receive guideline-recommended treatments for OHCA. The reasons for these differences require further exploration, and EMS provider education and training should specifically address these sex differences in the treatment of OHCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Pontari, Michel; Giusto, Laura

2013-11-01

To describe new developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel. The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition.

Temporary ventricular overdrive pacing for electrical storm after coronary artery bypass grafting.

PubMed

Yoshida, Toshihito; Naito, Yuji; Nishimura, Kuniharu

2011-11-01

A 57-year-old man who had been receiving chemotherapy for multiple myeloma complained of chest pain and was diagnosed with coronary artery disease. Coronary artery bypass grafting without cardiopulmonary bypass was performed smoothly, and extubation was done in the operating room. The next evening, cluster of ventricular tachycardia and fibrillation triggered by ventricular premature contractions occurred and required multiple electrical defibrillations. Despite intravenous administration of lidocaine, amiodarone, magnesium, and β-blocker, the storm sustained and was suppressed only by temporary ventricular overdrive pacing. He was discharged on foot.

Quantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?

PubMed Central

Chen, Y; Mao, J; Lin, J; Yu, H; Peters, S; Shebley, M

2016-01-01

This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent–metabolite pairs is described and guidance on strategic application is provided. PMID:27642087

Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kittel-Schneider, S; Spiegel, S; Renner, T; Romanos, M; Reif, A; Reichert, S; Heupel, J; Schnetzler, L; Stopper, H; Jacob, C

2016-07-01

Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss.

PubMed

Chen, Luguang; Ma, Chao; Bian, Yun; Li, Jing; Wang, Tiegong; Su, Li; Lu, Jianping

2017-01-01

Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future. © 2017 The Author(s). Published by S. Karger AG, Basel.

Healthcare professionals' perceptions of psychological treatment for chronic pain in Singapore: challenges, barriers, and the way forward.

PubMed

Yang, Su-Yin; Bogosian, Angeliki; Moss-Morris, Rona; McCracken, Lance M

2016-08-01

There are very few studies on healthcare providers' experiences of delivering treatment for chronic pain in a Southeast Asian setting. The aims of this study are to understand the experiences of professionals delivering treatment for people with chronic pain in Singapore and identify possible barriers to psychological treatment for this condition within the broader experiences of these professionals. Healthcare professionals with at least 1-year experience treating chronic pain were recruited and purposefully sampled. Fifteen inductive semi-structured interviews were conducted to explore healthcare professionals' experiences of treating people with chronic pain. Interviews were transcribed verbatim and analysed using thematic analysis. Four main themes were identified: 'System Barriers', 'Core Beliefs and management of Chronic Pain', 'Engaging Patients in treatment' and 'Creating Awareness for Chronic Pain Management'. Professionals trained in a multidisciplinary approach to pain management were seen as rare. Professionals who could refer patients for psychological treatment do not refer due to costs, and their perception that patients may lack understanding of such a treatment. Reducing barriers in the access to psychological treatment in settings like Singapore will require a multifaceted approach. Implications for Rehabilitation A multifaceted approach is required to reduce barriers to psychological treatment for chronic pain in settings like Singapore. Educating healthcare professionals on the need for a multidisciplinary approach to chronic pain could help in reducing misconceptions and increase understanding of the benefits of psychological approaches. Utilizing both media and technological platforms as a means to facilitate psychological treatment uptake for chronic pain may be a way forward for a technological savvy generation.

[Effect of Environmental Factors on the Ecotoxicity of Pharmaceuticals and Personal Care Products].

PubMed

Sugihara, Kazumi

2018-01-01

　In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.

[Magneto- laser-phoresis with heparin in the treatment of patients with chronic pharyngitis].

PubMed

Portenko, G M; Grafskaia, N A

2002-01-01

The results of treatment of various forms of chronic pharyngitis by magnetolaserophoresis (MLP) with heparin show that MLP is more effective in hypertrophic chronic pharyngitis. It is emphasized that when planning treatment of chronic pharyngitis one should take into consideration the state of the gastrointestinal tract.

[Incidence of phlebitis due to peripherally inserted venous catheters: impact of a catheter management protocol].

PubMed

Ferrete-Morales, C; Vázquez-Pérez, M A; Sánchez-Berna, M; Gilabert-Cerro, I; Corzo-Delgado, J E; Pineda-Vergara, J A; Vergara-López, S; Gómez-Mateos, J

2010-01-01

To assess the impact on the incidence of PPIVC by implementing a catheter management protocol and to determine risk factors for PPIVC development in hospitalized patients. A total of 3978 episodes of venous catheterization were prospectively included from September 2002 to December 2007. A catheter management protocol was implemented during this period of time. The incidence and variables associated to the occurrence of PPIVC were determined. The incidence of PPIVC from 2002 to 2007 was 4.8%, 4.3%, 3.6%, 2.5%, 1.3% and 1.8% (p<0.001). Perfusion of amiodarone [adjusted OR (AOR) 25.97; 95% CI=7.29-92.55, p=0.0001] and cefotaxime (AOR 2.90; 95% CI=1.29-6.52, p=0.01) and the shift when the catheters were placed (AOR for morning vs. night shift 0.60; 95% CI=0.35-1.02, p=0.063) were independently associated to the development of PPIVC. A history of phlebitis was the only factor independently associated to phlebitis due to peripherally inserted central venous catheters (AOR 3.24; CI at 95% CI= 1.05-9.98, p=0.04). A catheter management protocol decreases the incidence of PPIVC in hospitalized patients. The risk of PPIVC increases for peripherally inserted central venous catheters when the patients have a history of phlebitis and for peripheral venous catheters when amiodarone or cefotaxime are infused. Catheterization of peripheral veins performed during morning shifts is associated with a lower incidence of PPIVC when compared with night shift catheterizations.

Physical compatibility of various drugs with neonatal total parenteral nutrient solution during simulated Y-site administration.

PubMed

Fox, Laura M; Wilder, Alyson G; Foushee, Jaime A

2013-03-15

The physical compatibility of various drugs with neonatal total parenteral nutrient (TPN) solution during simulated Y-site administration was evaluated. Study drugs were selected based on the lack of compatibility data with them and neonatal TPN solution and the frequency of use in a local neonatal unit. These drugs included amiodarone, caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, midazolam, pentobarbital, phenobarbital, and rifampin. Equal volumes of neonatal TPN solution or sterile water for injection were combined with study drugs or sterile water for injection at concentrations used clinically in neonates. Each test was performed in triplicate. The samples were examined via turbidimetric analysis and visually against light and dark backgrounds immediately after mixing and at 0.25, 0.5, 1, 2, and 3 hours after mixing. Analysis of variance was used to determine statistically significant differences between the test and control solutions. Many of the drugs studied exhibited no visual or turbidimetric evidence of incompatibility when combined with neonatal TPN solution for up to three hours in a simulated Y-site injection. Pentobarbital, phenobarbital, and rifampin formed visible precipitation immediately after mixing with the neonatal TPN solution. Caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, and midazolam exhibited no visual or turbidimetric evidence of incompatibility when combined with a neonatal TPN solution for up to three hours in a simulated Y-site injection. Amiodarone, pentobarbital, phenobarbital, and rifampin were not compatible with the neonatal TPN solution and should not be coadministered via Y-site injection.

Analysis of clinical decision support system malfunctions: a case series and survey

PubMed Central

Wright, Adam; Hickman, Thu-Trang T; McEvoy, Dustin; Aaron, Skye; Ai, Angela; Andersen, Jan Marie; Hussain, Salman; Ramoni, Rachel; Fiskio, Julie; Sittig, Dean F; Bates, David W

2016-01-01

Objective To illustrate ways in which clinical decision support systems (CDSSs) malfunction and identify patterns of such malfunctions. Materials and Methods We identified and investigated several CDSS malfunctions at Brigham and Women’s Hospital and present them as a case series. We also conducted a preliminary survey of Chief Medical Information Officers to assess the frequency of such malfunctions. Results We identified four CDSS malfunctions at Brigham and Women’s Hospital: (1) an alert for monitoring thyroid function in patients receiving amiodarone stopped working when an internal identifier for amiodarone was changed in another system; (2) an alert for lead screening for children stopped working when the rule was inadvertently edited; (3) a software upgrade of the electronic health record software caused numerous spurious alerts to fire; and (4) a malfunction in an external drug classification system caused an alert to inappropriately suggest antiplatelet drugs, such as aspirin, for patients already taking one. We found that 93% of the Chief Medical Information Officers who responded to our survey had experienced at least one CDSS malfunction, and two-thirds experienced malfunctions at least annually. Discussion CDSS malfunctions are widespread and often persist for long periods. The failure of alerts to fire is particularly difficult to detect. A range of causes, including changes in codes and fields, software upgrades, inadvertent disabling or editing of rules, and malfunctions of external systems commonly contribute to CDSS malfunctions, and current approaches for preventing and detecting such malfunctions are inadequate. Conclusion CDSS malfunctions occur commonly and often go undetected. Better methods are needed to prevent and detect these malfunctions. PMID:27026616

Rational design and synthesis of water-compatible molecularly imprinted polymers for selective solid phase extraction of amiodarone.

PubMed

Muhammad, Turghun; Cui, Liu; Jide, Wang; Piletska, Elena V; Guerreiro, Antonio R; Piletsky, Sergey A

2012-01-04

Novel water-compatible molecularly imprinted polymers (MIPs) selective for amiodarone (AD) were designed via a new methodology which relies on screening library of non-imprinted polymers (NIPs). The NIP library consisted of eighteen cross-linked co-polymers synthesized from monomers commonly used in molecular imprinting. The binding capacity of each polymer in the library was analyzed in two different solvents. Binding in water was used to assess non-specific (hydrophobic) interactions and binding in an appropriate organic solvent was used to assess specific interactions. A good correlation was found between the screening tests and modeling of monomer-template interactions performed using computational approach. Additionally, analysis of template-monomer interactions was performed using UV-vis spectroscopy. As the result, 4-vinylpyridine (4-VP) was selected as the best monomer for developing MIP for AD. The 4-VP-based polymers demonstrated imprinting factor equal 3.9. The polymers performance in SPE was evaluated using AD and its structural analogues. The recovery of AD was as high as 96% when extracted from spiked phosphate buffer (pH 4.5) solution and 82.1% from spiked serum samples. The developed MIP shown as a material with specific binding to AD, comparing to its structural analogues, 1-(2-diethylaminoethoxy)-2,6-diiodo-4-nitrobenzene and lidocaine, which shown 9.9% and 25.4% of recovery from the buffer solution, correspondingly. We believe that the screening of NIP library could be proposed as an alternative to commonly used computational and combinatorial approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of sildenafil on cardiac repolarization.

PubMed

Chiang, Chern-En; Luk, Hsiang-Ning; Wang, Tsui-Min; Ding, Philip Yu-An

2002-08-01

Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats

PubMed Central

Valcheva-Kuzmanova, Stefka; Stavreva, Galya; Dancheva, Violeta; Terziev, Ljudmil; Atanasova, Milena; Stoyanova, Angelina; Dimitrova, Anelia; Shopova, Veneta

2014-01-01

Background: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. Objective: We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. Materials and Methods: AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when biochemical, cytological, and immunological assays were performed. Results: AMFJ antagonized AD-induced increase of the lung weight coefficient. In bronchoalveolar lavage fluid, AD increased significantly the protein content, total cell count, polymorphonuclear cells, lymphocytes and the activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not differ significantly from the control values. In lung tissue, AD induced oxidative stress measured by malondialdehyde content and fibrosis assessed by the hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL-10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that did not differ significantly from the control ones. Conclusion: AMFJ could have a protective effect against AD-induced pulmonary toxicity as evidenced by the reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation, and fibrosis. PMID:24914278

Effective physical treatment for chronic low back pain.

PubMed

Maher, C G

2004-01-01

It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

Chronic Myelogenous Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Chronic myelogenous leukemia treatments include tyrosine kinase inhibitors, high-dose therapy with allogeneic transplantation, and other medications. Get detailed information about chronic myelogenous leukemia (CML) treatment options in this summary for clinicians.

Chronic fatigue syndrome in the media: a content analysis of newspaper articles

PubMed Central

Knudsen, Ann Kristen; Omenås, Anne Nagelgaard; Harvey, Samuel B; Løvvik, Camilla MS; Lervik, Linn V; Mykletun, Arnstein

2011-01-01

Objectives Although cognitive behavioural therapy and graded exercise treatment are recognized evidence-based treatments for chronic fatigue syndrome/myalgic encephalomyelitis (ME), their use is still considered controversial by some patient groups. This debate has been reflected in the media, where many patients gather health information. The aim of this study was to examine how treatment for chronic fatigue syndrome/ME is described in the newspaper media. Design Content analysis of newspaper articles. Setting The digitalized media archive Atekst was used to identify Norwegian newspaper articles where chronic fatigue syndrome/ME was mentioned. Participants Norwegian newspaper articles published over a 20-month period, from 1 January 2008 to 31 August 2009. Main outcome measures Statements regarding efficiency of various types of treatment for chronic fatigue syndrome/ME and the related source of the treatment advice. Statements were categorized as being either positive or negative towards evidence-based or alternative treatment. Results One hundred and twenty-two statements regarding treatment of chronic fatigue syndrome/ME were identified among 123 newspaper articles. The most frequent statements were positive statements towards alternative treatment Lightning Process (26.2%), negative statements towards evidence-based treatments (22.1%), and positive statements towards other alternative treatment interventions (22.1%). Only 14.8% of the statements were positive towards evidence-based treatment. Case-subjects were the most frequently cited sources, accounting for 35.2% of the statements, followed by physicians and the Norwegian ME association. Conclusions Statements regarding treatment for chronic fatigue syndrome/ME in newspapers are mainly pro-alternative treatment and against evidence-based treatment. The media has great potential to influence individual choices. The unbalanced reporting of treatment options for chronic fatigue syndrome/ME in the media is potentially harmful. PMID:21637403

Chronic fatigue syndrome in the media: a content analysis of newspaper articles.

PubMed

Knudsen, Ann Kristen; Omenås, Anne Nagelgaard; Harvey, Samuel B; Løvvik, Camilla Ms; Lervik, Linn V; Mykletun, Arnstein

2011-05-01

Although cognitive behavioural therapy and graded exercise treatment are recognized evidence-based treatments for chronic fatigue syndrome/myalgic encephalomyelitis (ME), their use is still considered controversial by some patient groups. This debate has been reflected in the media, where many patients gather health information. The aim of this study was to examine how treatment for chronic fatigue syndrome/ME is described in the newspaper media. Content analysis of newspaper articles. The digitalized media archive Atekst was used to identify Norwegian newspaper articles where chronic fatigue syndrome/ME was mentioned. Norwegian newspaper articles published over a 20-month period, from 1 January 2008 to 31 August 2009. Statements regarding efficiency of various types of treatment for chronic fatigue syndrome/ME and the related source of the treatment advice. Statements were categorized as being either positive or negative towards evidence-based or alternative treatment. One hundred and twenty-two statements regarding treatment of chronic fatigue syndrome/ME were identified among 123 newspaper articles. The most frequent statements were positive statements towards alternative treatment Lightning Process (26.2%), negative statements towards evidence-based treatments (22.1%), and positive statements towards other alternative treatment interventions (22.1%). Only 14.8% of the statements were positive towards evidence-based treatment. Case-subjects were the most frequently cited sources, accounting for 35.2% of the statements, followed by physicians and the Norwegian ME association. Statements regarding treatment for chronic fatigue syndrome/ME in newspapers are mainly pro-alternative treatment and against evidence-based treatment. The media has great potential to influence individual choices. The unbalanced reporting of treatment options for chronic fatigue syndrome/ME in the media is potentially harmful.

Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery.

PubMed

Arsenault, Kyle A; Yusuf, Arif M; Crystal, Eugene; Healey, Jeff S; Morillo, Carlos A; Nair, Girish M; Whitlock, Richard P

2013-01-31

Atrial fibrillation is a common post-operative complication of cardiac surgery and is associated with an increased risk of post-operative stroke, increased length of intensive care unit and hospital stays, healthcare costs and mortality. Numerous trials have evaluated various pharmacological and non-pharmacological prophylactic interventions for their efficacy in preventing post-operative atrial fibrillation. We conducted an update to a 2004 Cochrane systematic review and meta-analysis of the literature to gain a better understanding of the effectiveness of these interventions. The primary objective was to assess the effects of pharmacological and non-pharmacological interventions for preventing post-operative atrial fibrillation or supraventricular tachycardia after cardiac surgery. Secondary objectives were to determine the effects on post-operative stroke or cerebrovascular accident, mortality, cardiovascular mortality, length of hospital stay and cost of treatment during the hospital stay. We searched the Cochrane Central Register of ControlLed Trials (CENTRAL) (Issue 8, 2011), MEDLINE (from 1946 to July 2011), EMBASE (from 1974 to July 2011) and CINAHL (from 1981 to July 2011). We selected randomized controlled trials (RCTs) that included adult patients undergoing cardiac surgery who were allocated to pharmacological or non-pharmacological interventions for the prevention of post-operative atrial fibrillation or supraventricular tachycardia, except digoxin, potassium (K(+)), or steroids. Two review authors independently abstracted study data and assessed trial quality. One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I(2) = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I(2) = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I(2) = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I(2) = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I(2) = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I(2) = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I(2) = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.

A closer look: Alternative pain management practices by heart failure patients with chronic pain.

PubMed

McDonald, Deborah Dillon; Soutar, Christina; Chan, Maria Agudelo; Afriyie, Angela

2015-01-01

To describe alternative non-pharmaceutical non-nutraceutical pain self-management strategies used by people with heart failure (HF) in order to reduce chronic non-cardiac pain. Little is known about alternative pain self-treatments used by HF patients with chronic pain. A cross-sectional descriptive design was used with 25 hospitalized HF patients who had chronic pain and used at least one alternative pain treatment. Pain intensity, pain interference with function, and current pain treatments were measured with the Brief Pain Inventory. Alternative treatments included walking, stretching, use of heat and cold. Five patients used evidence-based pain treatments for their chronic pain conditions. Patients reported moderate pain intensity and pain interference with activity. Patients with HF and chronic pain use few alternative pain treatments. Screening for chronic pain and referral to Integrative Medicine and/or Palliative care for a pain management consult might reduce the added burden of pain in people with HF. Copyright © 2015 Elsevier Inc. All rights reserved.

What's New in Chronic Lymphocytic Leukemia Research and Treatment?

MedlinePlus

... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Research ... help researchers learn more about how CLL develops. New drugs for chronic lymphocytic leukemia Dozens of new ...

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety.

PubMed

Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

2015-07-17

Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%-2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155-195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

PubMed Central

Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

2015-01-01

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

PubMed

Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

2015-01-01

The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

PubMed

Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules.

PubMed

Mackenzie, Louise S

2018-01-01

Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological processes including development, growth, metabolism, and cardiac function. The hyperthyroid condition results from an over production of thyroid hormones resulting in a continual stimulation of thyroid receptors which is detrimental for the patient. Therapies for hyperthyroidism are available, but there is a need for new small molecules that act as TR antagonists to treat hyperthyroidism. Many compounds exhibit TR antagonism and are considered detrimental to health. Some drugs in the clinic (most importantly, amiodarone) and environmental pollution exhibit TR antagonist properties and thus have the potential to induce hypothyroidism in some people. This chapter provides an overview of novel small molecules that have been specifically designed or screened for their TR antagonist activity as novel treatments for hyperthyroidism. While novel compounds have been identified, to date none have been developed sufficiently to enter clinical trials. Furthermore, a discussion on other sources of TR antagonists is discussed in terms of side effects of current drugs in the clinic as well as environmental pollution. © 2018 Elsevier Inc. All rights reserved.

Treatment options for chronic pancreatitis.

PubMed

Issa, Yama; Bruno, Marco J; Bakker, Olaf J; Besselink, Marc G; Schepers, Nicolien J; van Santvoort, Hjalmar C; Gooszen, Hein G; Boermeester, Marja A

2014-09-01

This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.

[Physical treatment modalities for chronic leg ulcers].

PubMed

Dissemond, J

2010-05-01

An increasing numbers of physical treatment options are available for chronic leg ulcer. In this review article, compression therapy, therapeutic ultrasound, negative pressure therapy, extracorporeal shock wave therapy, electrostimulation therapy, electromagnetic therapy, photodynamic therapy, water-filtered infrared-A-radiation and hydrotherapy are discussed in terms of their practical applications and the underlying evidence. With the exception of compression therapy for most of these treatments, good scientific data are not available. However this is a widespread problem in the treatment of chronic wounds. Nevertheless, several of the described methods such as negative pressure therapy represent one of the gold standards in practical treatment of patients with chronic leg ulcers. Although the use of physical treatment modalities may improve healing in patients with chronic leg ulcers, the diagnosis and treatment of the underlying causes are essential for long-lasting success.

Effectiveness of an Extended Yoga Treatment for Women with Chronic Posttraumatic Stress Disorder.

PubMed

Price, Maggi; Spinazzola, Joseph; Musicaro, Regina; Turner, Jennifer; Suvak, Michael; Emerson, David; van der Kolk, Bessel

2017-04-01

Yoga has been found to be an effective posttraumatic stress disorder (PTSD) treatment for a variety of trauma survivors, including females with chronic PTSD. Aim/Purpose: The current study builds on extant research by examining an extended trauma-sensitive yoga treatment for women with chronic PTSD. The study sought to optimize the results of a treatment protocol examined in a recent randomized controlled trial with a shorter duration and without assignment or monitoring of home practice. The authors examined a 20-week trauma-sensitive yoga treatment in a non-randomized single-group treatment feasibility study for women with chronic treatment-resistant PTSD (N = 9). The authors examined PTSD and dissociation symptom reduction over several assessment periods. The results indicate that participants experienced significant reductions in PTSD and dissociative symptomatology above and beyond similar treatments of a shorter duration. The findings suggest that more intensive trauma-sensitive yoga treatment characterized by longer duration and intentional assignment and monitoring of home practice may be more advantageous for individuals with severe and chronic PTSD. The implications of the findings for the potentially more substantial role of yoga as an intervention for a subset of adults with chronic treatment-resistant PTSD are discussed.

First-line treatment of chronic myeloid leukaemia.

PubMed

O'Dwyer, Michael

2010-02-01

Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase.

Healing of chronic wounds with adjunctive ablative fractional laser resurfacing in two pediatric patients.

PubMed

Krakowski, Andrew C; Diaz, Lucia; Admani, Shehla; Uebelhoer, Nathan S; Shumaker, Peter R

2016-02-01

The development of chronic non-healing wounds is multifactorial and can lead to increased patient morbidity. When traditional wound care methods fail, alternative treatments are needed to prevent chronic ulcer complications. Ablative fractional laser resurfacing (AFR) is an emerging therapy for chronic wounds. We report the successful use of AFR to facilitate the healing of chronic wounds in two pediatric patients. This is a case series including two patients with chronic wounds within scars that were treated with a micro-fractionated carbon dioxide (CO2 ) laser in a single pass at a pulse energy of 50 mJ and a treatment density of 5%. One patient had one treatment and the other had two treatments 1 month apart. AFR led to rapid healing of chronic wounds in both pediatric patients. The wounds remained epithelialized after 9 months in one patient and 4 months in the other. There were no complications. The combination of tolerability and efficacy observed in these cases introduces AFR as a potential promising adjunct to existing treatments for chronic, non-healing wounds in the pediatric population. © 2015 Wiley Periodicals, Inc.

Microbial Biofilms and Chronic Wounds

PubMed Central

Omar, Amin; Wright, J. Barry; Schultz, Gregory; Burrell, Robert; Nadworny, Patricia

2017-01-01

Background is provided on biofilms, including their formation, tolerance mechanisms, structure, and morphology within the context of chronic wounds. The features of biofilms in chronic wounds are discussed in detail, as is the impact of biofilm on wound chronicity. Difficulties associated with the use of standard susceptibility tests (minimum inhibitory concentrations or MICs) to determine appropriate treatment regimens for, or develop new treatments for use in, chronic wounds are discussed, with alternate test methods specific to biofilms being recommended. Animal models appropriate for evaluating biofilm treatments are also described. Current and potential future therapies for treatment of biofilm-containing chronic wounds, including probiotic therapy, virulence attenuation, biofilm phenotype expression attenuation, immune response suppression, and aggressive debridement combined with antimicrobial dressings, are described. PMID:28272369

[Thought and method of classic formulae in treatment of chronic cough].

PubMed

Su, Ke-Lei; Zhang, Ye-Qing

2018-06-01

Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction. Copyright© by the Chinese Pharmaceutical Association.

Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

PubMed Central

Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

2012-01-01

Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

First-line treatment of chronic myeloid leukaemia

PubMed Central

O'Dwyer, Michael

2010-01-01

Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase. PMID:23556068

Assessing United States Patient and Dermatologist Experiences with Severe Chronic Hand Eczema

PubMed Central

Baranowski, Eileen; Zelt, Susan; Reynolds, Maria; Sherrill, Beth

2015-01-01

Objective: Patients with severe chronic hand eczema often have persistent symptoms that interfere with daily activities, social functioning, and employment. Many patients are refractory to topical corticosteroids. This survey-based study was performed to characterize treatment experiences, impact on productivity, and quality of life of patients with severe chronic hand eczema; understand dermatologists’ severe chronic hand eczema treatment patterns. Design: A web-based survey in the United States queried pre-identified patients with severe chronic hand eczema regarding symptoms, treatment history, quality of life, work productivity, treatment satisfaction, and healthcare utilization. In a separate survey, dermatologists were asked about treatment patterns and satisfaction with currently available therapies. Results: The most commonly reported symptoms currently experienced by patients (n=163) were dryness/flaking (81%), itchiness (75%), and cracking/tearing of the skin (71%). Over the last three months, 84 percent of patients with severe chronic hand eczema self-reported using topical steroids, and 30 percent used systemic corticosteroids or retinoids. Approximately 30 percent reported impairment while working and productivity loss. Patient quality of life was negatively impacted. Dermatologists (n=125) reported most often treating severe chronic hand eczema with topical corticosteroids (99%), followed by topical immunomodulators (71%) and systemic treatments (70%). Only two percent were very satisfied with currently available products. Conclusion: Patients with severe chronic hand eczema experience symptoms that negatively impact work productivity and quality of life. Few dermatologists are very satisfied with currently available severe chronic hand eczema treatment options. PMID:26705436

Surface atrial frequency analysis in patients with atrial fibrillation: a tool for evaluating the effects of intervention.

PubMed

Raine, Dan; Langley, Philip; Murray, Alan; Dunuwille, Asunga; Bourke, John P

2004-09-01

The aims of this study were to evaluate (1) principal component analysis as a technique for extracting the atrial signal waveform from the standard 12-lead ECG and (2) its ability to distinguish changes in atrial fibrillation (AF) frequency parameters over time and in response to pharmacologic manipulation using drugs with different effects on atrial electrophysiology. Twenty patients with persistent AF were studied. Continuous 12-lead Holter ECGs were recorded for 60 minutes, first, in the drug-free state. Mean and variability of atrial waveform frequency were measured using an automated computer technique. This extracted the atrial signal by principal component analysis and identified the main frequency component using Fourier analysis. Patients were then allotted sequentially to receive 1 of 4 drugs intravenously (amiodarone, flecainide, sotalol, or metoprolol), and changes induced in mean and variability of atrial waveform frequency measured. Mean and variability of atrial waveform frequency did not differ within patients between the two 30-minute sections of the drug-free state. As hypothesized, significant changes in mean and variability of atrial waveform frequency were detected after manipulation with amiodarone (mean: 5.77 vs 4.86 Hz; variability: 0.55 vs 0.31 Hz), flecainide (mean: 5.33 vs 4.72 Hz; variability: 0.71 vs 0.31 Hz), and sotalol (mean: 5.94 vs 4.90 Hz; variability: 0.73 vs 0.40 Hz) but not with metoprolol (mean: 5.41 vs 5.17 Hz; variability: 0.81 vs 0.82 Hz). A technique for continuously analyzing atrial frequency characteristics of AF from the surface ECG has been developed and validated.

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.

PubMed

Kulier, A H; Novalija, E; Hogan, Q; Vicenzi, M N; Woehlck, H J; Bajic, J; Atlee, J L; Bosnjak, Z J

1999-12-01

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Analysis of clinical decision support system malfunctions: a case series and survey.

PubMed

Wright, Adam; Hickman, Thu-Trang T; McEvoy, Dustin; Aaron, Skye; Ai, Angela; Andersen, Jan Marie; Hussain, Salman; Ramoni, Rachel; Fiskio, Julie; Sittig, Dean F; Bates, David W

2016-11-01

To illustrate ways in which clinical decision support systems (CDSSs) malfunction and identify patterns of such malfunctions. We identified and investigated several CDSS malfunctions at Brigham and Women's Hospital and present them as a case series. We also conducted a preliminary survey of Chief Medical Information Officers to assess the frequency of such malfunctions. We identified four CDSS malfunctions at Brigham and Women's Hospital: (1) an alert for monitoring thyroid function in patients receiving amiodarone stopped working when an internal identifier for amiodarone was changed in another system; (2) an alert for lead screening for children stopped working when the rule was inadvertently edited; (3) a software upgrade of the electronic health record software caused numerous spurious alerts to fire; and (4) a malfunction in an external drug classification system caused an alert to inappropriately suggest antiplatelet drugs, such as aspirin, for patients already taking one. We found that 93% of the Chief Medical Information Officers who responded to our survey had experienced at least one CDSS malfunction, and two-thirds experienced malfunctions at least annually. CDSS malfunctions are widespread and often persist for long periods. The failure of alerts to fire is particularly difficult to detect. A range of causes, including changes in codes and fields, software upgrades, inadvertent disabling or editing of rules, and malfunctions of external systems commonly contribute to CDSS malfunctions, and current approaches for preventing and detecting such malfunctions are inadequate. CDSS malfunctions occur commonly and often go undetected. Better methods are needed to prevent and detect these malfunctions. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

The presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) does not exclude the diagnosis of type 2 amiodarone-induced thyrotoxicosis.

PubMed

Tomisti, L; Urbani, C; Rossi, G; Latrofa, F; Sardella, C; Manetti, L; Lupi, I; Marcocci, C; Bartalena, L; Curzio, O; Martino, E; Bogazzi, F

2016-05-01

It is widely accepted that type 2 amiodarone-induced thyrotoxicosis (AIT) generally occurs in patients with a normal thyroid gland without signs of thyroid autoimmunity. However, it is currently unknown if the presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) in AIT patients without other signs of an underlying thyroid disease may impair the response to glucocorticoid therapy. We performed a pilot retrospective cohort study with matched-subject design and an equivalence hypothesis, comparing the response to glucocorticoid therapy between 20 AIT patients with a normal thyroid gland, low radioiodine uptake, undetectable TSH receptor antibodies and positive TgAb and/or TPOAb (Ab+ group), and 40 patients with the same features and absent thyroid antibodies (Ab- group). The mean cure time was 54 ± 68 days in the Ab+ group and 55 ± 49 days in the Ab- group (p = 0.63). The equivalence test revealed an equivalent cure rate after 60, 90 and 180 days (p = 0.67, 0.88 and 0.278, respectively). The occurrence of permanent hypothyroidism was higher in the Ab+ group than in the Ab- group (26.3 vs 5.13 %, p = 0.032). The presence of TgAb and/or TPOAb does not affect the response to glucocorticoid therapy, suggesting that the patients with features of destructive form of AIT should be considered as having a type 2 AIT irrespective of the presence of TGAb or TPOAb. These patients have a higher risk of developing hypothyroidism after the resolution of thyrotoxicosis and should be monitored accordingly.

Improvement of the myocardial performance index in atrial fibrilation patients treated with amiodarone after cardioversion.

PubMed

Besli, Feyzullah; Basar, Cengiz; Kecebas, Mesut; Turker, Yasin

2015-03-01

This study evaluated the response to electrical cardioversion (EC) and the effect on the myocardial performance index (MPI) in patients with persistent and long-standing persistent atrial fibrillation (AF). We enrolled 103 patients (mean age 69.6 ± 8.9 years, 40.7% males) with a diagnosis of persistent and long-standing persistent AF. EC was applied to all patients after one g of amiodarone administration. Echocardiographic findings before EC were compared in patients with successful versus unsuccessful cardioversions and in patients with maintained sinus rhythm (SR) versus those with AF recurrence at the end of the first month. We also compared echocardiographic data before EC versus at the end of the first month in the same patients with maintained SR. SR was achieved in 72.8% of patients and was continued at the end of the first month in 69.3% of the patients. The MPI value of all patients was found to be 0.73 ± 0.21. The size of the left atrium was determined to be an independent predictor of the maintenance of SR at 1 month. In subgroup analyses, when we compared echocardiographic findings before EC and at the end of the first month in patients with maintained SR, the MPI (0.66 ± 0.14 vs 0.56 ± 0.09, p < 0.001) values were significantly decreased. Our study is the first to show impairment of the MPI, which is an indicator of systolic and diastolic function, in patients with persistent and long-standing persistent AF and improvement of the MPI after successful EC.

In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias.

PubMed

Gautier, Patrick; Serre, Martine; Cosnier-Pucheu, Sylvie; Djandjighian, Laurent; Roccon, Alain; Herbert, Jean-Marc; Nisato, Dino

2005-02-01

SSR149744C (2-butyl-3-{4-[3-(dibutylamino)propyl]benzoyl}-1-benzofuran-5-carboxylate isopropyl fumarate) is a new noniodinated benzofuran derivative structurally related to amiodarone and dronedarone that is currently undergoing clinical trials as an antiarrhythmic agent. As SSR149744C exhibits electrophysiological and hemodynamic properties of class I, II, III, and IV antiarrhythmic agents, the aim of this study was to evaluate its acute intravenous (IV) or oral (PO) antiarrhythmic activities in in vitro and in vivo animal models of atrial and ventricular arrhythmias. In vagally induced atrial fibrillation (AF) in anesthetized dogs, SSR149744C (3 and 10 mg/kg IV) terminated AF in all 7 dogs and prevented reinduction in 4 out of 7 dogs; effective refractory periods of right atrium were dose-dependently and frequency-independently lengthened. In low-K+ medium-induced AF models, SSR149744C (0.1 to 1 microM) prevented AF in isolated guinea pig hearts in a concentration-dependent manner. At the ventricular level, SSR149744C (0.1 to 10 mg/kg IV and 3 to 90 mg/kg PO) prevented reperfusion-induced arrhythmias in anesthetized rats with a dose-effect relationship, and, at doses of 30 to 90 mg/kg PO, it reduced early (0-24 hours) mortality following permanent left coronary artery ligature in conscious rats. The present results show that SSR149744C is an effective antiarrhythmic agent in atrial fibrillation and in ventricular arrhythmias. Like amiodarone and dronedarone, its efficiency in these animal models of arrhythmias is likely be related to its multifactorial mechanism of action.

Chronic orchialgia: Review of treatments old and new

PubMed Central

Tojuola, Bayo; Layman, Jeffrey; Kartal, Ibrahim; Gudelogul, Ahmet; Brahmbhatt, Jamin; Parekattil, Sijo

2016-01-01

Introduction: Chronic orchialgia is historically and currently a challenging disease to treat. It is a diagnostic and therapeutic challenge for physicians. Conservative therapy has served as the first line of treatment. For those who fail conservative therapy, surgical intervention may be required. We aim to provide a review of currently available surgical options and novel surgical treatment options. Methods: A review of current literature was performed using PubMed. Literature discussing treatment options for chronic orchialgia were identified. The following search terms were used to identify literature that was relevant to this review: Chronic orchialgia, testicular pain, scrotal content pain, and microsurgical denervation of the spermatic cord (MDSC). Results: The incidence of chronic orchialgia has been increasing over time. In the USA, it affects up to 100,000 men per year due to varying etiologies. The etiology of chronic orchialgia can be a confounding problem. Conservative therapy should be viewed as the first line therapy. Studies have reported poor success rates. Current surgical options for those who fail conservative options include varicocelectomy, MDSC, epididymectomy, and orchiectomy. Novel treatment options include microcryoablation of the peri-spermatic cord, botox injection, and amniofix injection. Conclusion: Chronic orchialgia has been and will continue to be a challenging disease to treat due to its multiple etiologies and variable treatment outcomes. Further studies are needed to better understand the problem. Treatment options for patients with chronic orchialgia are improving. Additional studies are warranted to better understand the long-term durability of this treatment options. PMID:26941490

Comparative effectiveness of exercise, acupuncture, and spinal manipulation for low back pain.

PubMed

Standaert, Christopher J; Friedly, Janna; Erwin, Mark W; Lee, Michael J; Rechtine, Glenn; Henrikson, Nora B; Norvell, Daniel C

2011-10-01

Systematic review. We sought to answer the following clinical questions: (1) Is structured exercise more effective in the treatment of chronic low back pain (LBP) than spinal manipulative therapy (SMT)? (2) Is structured exercise more effective in the treatment of chronic LBP than acupuncture? (3) Is SMT more effective in the treatment of chronic LBP than acupuncture? (4) Do certain subgroups respond more favorably to specific treatments? (5) Are any of these treatments more cost-effective than the others? Exercise, SMT, and acupuncture are widely used interventions in the treatment of chronic LBP. There is evidence that all of these approaches may offer some benefit for patients with chronic LBP when compared with usual care or no treatment. The relative benefits or cost-effectiveness of any one of these treatments when compared with the others are less well-defined, and it is difficult to identify specific subgroups of those with chronic LBP who may preferentially respond to a particular treatment modality. A systematic review of the literature was performed to identify randomized controlled trials comparing a structured exercise program, SMT, or acupuncture with one another in patients with chronic LBP. Two studies were identified comparing the use of structured exercise with SMT that met our inclusion criteria. Although these studies utilized different approaches for the exercise and SMT treatment groups, patients in both groups improved in terms of pain and function in both studies. Using random-effects modeling, there was no difference between the exercise and SMT groups when the data from these studies were pooled. We identified no studies meeting our inclusion criteria that compared acupuncture with either structured exercise or SMT or that addressed the relative cost-effectiveness of these approaches in the treatment of patients with chronic LBP. The studies identified indicate that structured exercise and SMT appear to offer equivalent benefits in terms of pain and functional improvement for those with chronic LBP with clinical benefits evident within 8 weeks of care. However, the level of evidence is low. There is insufficient evidence to comment on the relative benefit of acupuncture compared with either structured exercise or SMT or to address the differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is also insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP. Structured exercise and SMT appear to offer equivalent benefits in the management of pain and function for patients with nonspecific chronic LBP. If no clinical benefit is appreciated after using one of these approaches for 8 weeks, then the treatment plan should be reevaluated and consideration should be given to modifying the treatment approach or using alternate forms of care. Strength of recommendation: Weak.There is insufficient evidence regarding the relative benefits of the acupuncture compared with either structured exercise or SMT in the treatment of chronic LBP.There is insufficient evidence to address differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP.

Effectiveness of an Extended Yoga Treatment for Women with Chronic Posttraumatic Stress Disorder

PubMed Central

Price, Maggi; Musicaro, Regina; Turner, Jennifer; Suvak, Michael; Emerson, David; van der Kolk, Bessel

2017-01-01

Abstract Background: Yoga has been found to be an effective posttraumatic stress disorder (PTSD) treatment for a variety of trauma survivors, including females with chronic PTSD. Aim/Purpose: The current study builds on extant research by examining an extended trauma-sensitive yoga treatment for women with chronic PTSD. The study sought to optimize the results of a treatment protocol examined in a recent randomized controlled trial with a shorter duration and without assignment or monitoring of home practice. Materials and Methods: The authors examined a 20-week trauma-sensitive yoga treatment in a non-randomized single-group treatment feasibility study for women with chronic treatment-resistant PTSD (N = 9). The authors examined PTSD and dissociation symptom reduction over several assessment periods. Results: The results indicate that participants experienced significant reductions in PTSD and dissociative symptomatology above and beyond similar treatments of a shorter duration. Conclusions: The findings suggest that more intensive trauma-sensitive yoga treatment characterized by longer duration and intentional assignment and monitoring of home practice may be more advantageous for individuals with severe and chronic PTSD. The implications of the findings for the potentially more substantial role of yoga as an intervention for a subset of adults with chronic treatment-resistant PTSD are discussed. PMID:28121466

Accounting for frailty when treating chronic diseases.

PubMed

Onder, Graziano; Vetrano, Davide L; Marengoni, Alessandra; Bell, J Simon; Johnell, Kristina; Palmer, Katie

2018-03-08

Chronic diseases are considered to be major determinants of frailty and it could be hypothesized that their treatment may counteract the development of frailty. However, the hypothesis that intensive treatment of chronic diseases might reduce the progression of frailty is poorly supported by existing studies. In contrast, some evidence suggests that intensive treatment of chronic diseases may increase negative health outcomes in frail older adults. In particular, if treatment of symptoms related to chronic diseases (i.e. pain in osteoarthritis, dyspnoea in respiratory disease, motor symptoms in Parkinson disease) might potentially reverse frailty, the benefits related to preventive pharmacological treatment of chronic diseases (i.e. antihypertensive treatment) in patients with prevalent frailty is not certain. In particular, several factors might alter the risk/benefit ratio of a given treatment in persons with frailty. These include: exclusion of frail persons from clinical studies, reduced life expectancy in frail persons, increased susceptibility to iatrogenic events, and functional deficits associated with frailty. Therefore, frailty acts as an effect modifier, by modifying the risks and benefits of chronic disease treatments. This hypothesis must be considered and tested in future clinical intervention studies and clinical guidelines should provide specific recommendations for the treatment of frail people, underlining the pros and the cons of pharmacological treatment and possible targets for therapy in this population. Meanwhile, in older patients, the prescribing process should be individualized and flexible. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

How Is Chronic Myeloid Leukemia Diagnosed?

MedlinePlus

... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats

PubMed Central

Fischli, W.; Hefti, F.; Clozel, J.-P.

1989-01-01

1 The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radio-active microspheres technique. 2 Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 ± 7 to 140 241 ± 7 mm Hg (P < 0.001), chronic treatment (1 × 10 mg kg-1 day-1 orally for 9 weeks) from 191 ± 5 to 122 ± 3 mm Hg P < 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P < 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P < 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P < 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3 With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P < 0.001) and natriuresis (+124% and +111%, P < 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4 It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation. In addition, diuretic and natriuretic effects of cilazapril probably contribute to blood pressure reduction. PMID:2527529

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

PubMed

Martin, N K; Foster, G R; Vilar, J; Ryder, S; Cramp, M E; Gordon, F; Dillon, J F; Craine, N; Busse, H; Clements, A; Hutchinson, S J; Ustianowski, A; Ramsay, M; Goldberg, D J; Irving, W; Hope, V; De Angelis, D; Lyons, M; Vickerman, P; Hickman, M

2015-04-01

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence. © 2014 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact

PubMed Central

Martin, N K; Foster, G R; Vilar, J; Ryder, S; E Cramp, M; Gordon, F; Dillon, J F; Craine, N; Busse, H; Clements, A; Hutchinson, S J; Ustianowski, A; Ramsay, M; Goldberg, D J; Irving, W; Hope, V; De Angelis, D; Lyons, M; Vickerman, P; Hickman, M

2015-01-01

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37–48% HCV chronic prevalence among PWID), East London (37–48%), Manchester (48–56%), Nottingham (37–44%), Plymouth (30–37%), Dundee (20–27%) and North Wales (27–33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33–57%] and 61% genotypes 2/3 [95%CI 47–76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence. PMID:25288193

[Use of decamethoxine in the complex treatment of chronic bronchitis].

PubMed

Iukhimets, V A; Pilipchuk, V N

1990-02-01

Seventy-two patients with chronic bronchitis were examined and divided into 3 groups. Group I consisted of patients with chronic catarrhal bronchitis (CCB) group II of those with chronic purulent bronchitis (CPB), group III of subjects with bronchitis associated with purulent destructive pulmonary diseases. All the patients received combined treatment with decamethoxin as an antibacterial modality. It was found that decamethoxin promotes elimination of the infection of the bronchial secretion in 60% of chronic bronchitis suffers, the incidence of microorganisms resistent to several antibiotics reduced 2-fold. Local use of decamethoxin as an antibacterial and antiinflammatory drug in multimodality treatment of chronic purulent bronchitis proved highly effective.

[Efficiency of etiologic correction of concomitant ascaridosis in the complex treatment of chronic pancreatitis].

PubMed

Babinets', L S; Droniak, Iu V; Pliashko, K O; Babinets', A I

2014-11-01

The of antihelmintic preparation albendazole using in the complex treatment of patients with chronic pancreatitis with the concomitant ascaridosis was promote regression of clinical demonstration of basic and concomitant diseases (P < 0.05). Options of coprogram and the structural state of pancreas from data of ultrasonography in marks by Marseille-Cambridge classification of chronic pancreatitis, after the conducted treatment became the better (P < 0.05), that established expedience of the use of albendazole in complex treatment of patients with a chronic pancreatitis with a concomitant ascaridosis.

Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

PubMed

Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

2009-01-01

Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

Role of Alternative Therapies for Chronic Pain Syndromes.

PubMed

Thomas, Donna-Ann; Maslin, Benjamin; Legler, Aron; Springer, Erin; Asgerally, Abbas; Vadivelu, Nalini

2016-05-01

There is increasing interest in the use of complimentary and alternative medicine (CAM) for the treatment of chronic pain. This review examines alternative and complimentary therapies, which can be incorporated as part of a biopsychosocial approach in the treatment of chronic pain syndromes. In the present investigation, literature from articles indexed on PubMed was evaluated including topics of alternative therapies, complimentary therapies, pain psychology, biofeedback therapy, physical exercise therapies, acupuncture, natural and herbal supplements, whole-body cryotherapy, and smartphone technologies in the treatment of chronic pain syndromes. This review highlights the key role of psychology in the treatment of chronic pain. Cognitive behavior therapy appears to be the most impactful while biofeedback therapy has also been shown to be effective for chronic pain. Exercise therapy has been shown to be effective in short-, intermediate-, and long-term pain states. When compared to that in sham controls, acupuncture has shown some benefit for neck pain immediately after the procedure and in the short term and improvement has also been demonstrated in the treatment of headaches. The role of smartphones and whole-body cryotherapy are new modalities and further studies are needed. Recent literature suggests that several alternate therapies could play a role in the treatment of chronic pain, supporting the biopsychosocial model in the treatment of pain states.

Do We Know What Causes Chronic Myeloid Leukemia?

MedlinePlus

... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Chronic illness histories of adults entering treatment for co-occurring substance abuse and other mental health disorders.

PubMed

Chesher, Nicholas J; Bousman, Chad A; Gale, Maiken; Norman, Sonya B; Twamley, Elizabeth W; Heaton, Robert K; Everall, Ian P; Judd, Patricia A

2012-01-01

Little is known about the medical status of individuals entering treatment for co-occurring substance abuse and other mental disorders (COD). We analyzed the medical histories of 169 adults entering outpatient treatment for CODs, estimating lifetime prevalence of chronic illness and current smoking, comparing these rates to the general population, and examining psychiatric and substance-related correlates of chronic illness. Results revealed significantly higher prevalence of hypertension, asthma, arthritis, and smoking compared to the general US population, and showed an association between chronic illness and psychiatric symptom distress and substance use severity. Findings support integration of chronic illness management into COD treatment.  Copyright © American Academy of Addiction Psychiatry.

Does complementary and alternative medicine (CAM) use reduce negative life impact of headaches for chronic migraineurs? A national survey.

PubMed

Lee, Jieun; Bhowmick, Amrita; Wachholtz, Amy

2016-01-01

Chronic migraine is a disabling condition that impacts multiple aspects of migraineurs' lives. Although pharmacological treatments can help to treat the pain associated with migraine headache, chronic migraineurs often experience side-effects of pharmacological treatments. Those experiences may contribute to the observed growth in complementary and alternative medicine (CAM) use among migraineurs. Relatively little is known about the patterns of CAM treatment and the characteristics of chronic migraineurs. Therefore, the purpose of the present study is to investigate the characteristics of chronic migraineurs who use CAM treatment and the relationship among satisfaction with current CAM use, negative life impact, migraine outcomes, and psychiatric comorbidities among chronic migraineurs. 2907 participants were recruited from a well-known online migraine headache resource. All participants were US adults aged 18 years or older. Migraineurs are referred to this website through various routes (e.g., referral from healthcare providers, internet search, obtaining information from research papers, personal invitation from other users, and information shared on social media etc.). Participants completed a 30-min self-report-survey in the spring of 2014. Almost half of the participants reported that they are currently using more than three different CAM treatments even though the majority of the participants reported neutral or dissatisfied with their current CAM treatment. Chronic migraineurs who use CAM treatments were more likely to experience prolonged or frequent migraine headaches (p = .018, η(2) = .0021), and experience greater negative life impact from their headaches (p = .000, η(2) = .0172) compared to non-CAM users. CAM treatment satisfaction was inversely related to the number of psychiatric comorbidities, frequency of migraines, and number of migraine symptoms (p's < .05). However, CAM treatment satisfaction was more strongly correlated with migraine outcomes than psychiatric comorbidities. Chronic migraineurs often pursue multiple CAM treatments in spite of low levels of satisfaction with those treatments. Patients who experience relief from traditional treatments are less likely to seek the out additional CAM treatments. Thus it is often the sicker migraine patients who use CAM. More attention is needed to consider migraine treatment resistance, and psychological factors in planning the treatment of chronic migraineurs as those factors may play an important role in treatment choices by patients.

[Radiofrequency catheter ablation in children with Wolff-Parkinson-White syndrome and sudden cardiac death who had been resuscitated].

PubMed

Benito Bartolomé, F; Sánchez Fernández-Bernal, C

2001-04-01

Sudden death may be the first manifestation of the Wolff-Parkinson-White syndrome, especially in children and adolescents. The aim of this study was to evaluate the usefulness of radiofrequency catheter ablation in children with Wolff-Parkinson-White syndrome with aborted sudden death. We report four patients with Wolff-Parkinson-White syndrome who survived cardiac arrest. The patients were aged from 2.5 months to 16 years. The two first patients were lactating infants; in the first sudden death occurred during digoxin treatment for supraventricular tachycardia secondary to Wolff-Parkinson-White syndrome and in the second the syndrome was diagnosed after an episode of sudden death. In these patients a free wall accessory pathway (left posterior and left lateral, respectively) was successfully ablated using a transseptal approach. The third patient was diagnosed with asymptomatic Wolff-Parkinson-White syndrome; sudden death occurred during exercise. In the fourth patient, sudden death occurred after intravenous therapy with adenosine triphosphate and amiodarone for rapid atrial fibrillation. In both patients, one accessory pathway, located in right posteroseptal and right anterior free wall, respectively, was ablated. After a mean follow-up of 43.5 26.4 months, no recurrence of sudden death had occurred and electrocardiogram showed sinus rhythm without delta wave. The third patient presented severe sequelae of hypoxemic encephalopathy, which persisted during the follow-up. Radiofrequency catheter ablation is the treatment of choice in Wolff-Parkinson-White syndrome with episodes of aborted sudden death.

Management of ventricular tachycardia in the ablation era: results of the European Heart Rhythm Association Survey.

PubMed

Tilz, Roland Richard; Lenarczyk, Radoslaw; Scherr, Daniel; Haugaa, Kristina Herman; Iliodromitis, Konstantinos; Pürerfellner, Helmut; Kiliszek, Marek; Dagres, Nikolaos

2018-01-01

Patients with sustained ventricular tachycardia (VT) are at risk of sudden death. Treatment options for VT include antiarrhythmic drug therapy, insertion of an implantable cardioverter-defibrillator, and catheter ablation. Evidence on indications for VT ablation, timing, ablation strategies, and periprocedural management is sparse. The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate clinical practice regarding management of VT among the European countries. An electronic questionnaire was sent to members of the EHRA Electrophysiology Research Network. Responses were received from 88 centres in 12 countries. The results have shown that management of VTs is very heterogeneous across the participating centres. Indications, periprocedural management, and ablation strategies vary substantially. This EP Wire survey has revealed that catheter ablation is the first-line therapy for the treatment of recurrent monomorphic stable VT in patients without structural heart disease as well as in patients with ischaemic cardiomyopathy and impaired left ventricular ejection fraction in the majority of centres. Furthermore, in patients with ischaemic cardiomyopathy and the first episode of monomorphic VT, most centres (62.0%) performed catheter ablation. On the contrary, in patients with non-ischaemic cardiomyopathy, amiodarone (41.4%) and catheter ablation (37.1%) are used in a very similar proportion. Ablation strategies, endpoints, and post-ablation antithrombotic management vary substantially among European centres. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Optimizing patient treatment decisions in an era of rapid technological advances: the case of hepatitis C treatment.

PubMed

Liu, Shan; Brandeau, Margaret L; Goldhaber-Fiebert, Jeremy D

2017-03-01

How long should a patient with a treatable chronic disease wait for more effective treatments before accepting the best available treatment? We develop a framework to guide optimal treatment decisions for a deteriorating chronic disease when treatment technologies are improving over time. We formulate an optimal stopping problem using a discrete-time, finite-horizon Markov decision process. The goal is to maximize a patient's quality-adjusted life expectancy. We derive structural properties of the model and analytically solve a three-period treatment decision problem. We illustrate the model with the example of treatment for chronic hepatitis C virus (HCV). Chronic HCV affects 3-4 million Americans and has been historically difficult to treat, but increasingly effective treatments have been commercialized in the past few years. We show that the optimal treatment decision is more likely to be to accept currently available treatment-despite expectations for future treatment improvement-for patients who have high-risk history, who are older, or who have more comorbidities. Insights from this study can guide HCV treatment decisions for individual patients. More broadly, our model can guide treatment decisions for curable chronic diseases by finding the optimal treatment policy for individual patients in a heterogeneous population.

Reserve-building activities attenuate treatment burden in chronic illness: The mediating role of appraisal and social support

PubMed Central

Schwartz, Carolyn E; Zhang, Jie; Michael, Wesley; Eton, David T; Rapkin, Bruce D

2018-01-01

This study examines the importance of four psychosocial factors—personality, cognitive appraisal of quality of life, social support, and current reserve-building—in predicting treatment burden in chronically ill patients. Chronically ill patients (n = 446) completed web-based measures. Structural equation modeling was used to investigate psychosocial factors predicting treatment burden. Reserve-building activities indirectly reduced treatment burden by: (1) reducing health worries appraisals, (2) reducing financial difficulties, (3) increasing calm and peaceful appraisals, and (4) increasing perceived social support. These findings point to key behaviors that chronically ill people can use to attenuate their treatment burden. PMID:29785278

78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment... antiviral (DAA) drugs for the treatment of chronic hepatitis C. This guidance revises and replaces a...

Treatment of chronic extensor tendons lesions of the fingers.

PubMed

Bellemère, P

2015-09-01

Chronic finger extensor apparatus injuries are the result of the initial acute treatment having failed or being flawed. Because of their chronic nature, these injuries present various amounts of tendon retraction, tendon callus lengthening, peritendinous scar adhesions, static and dynamic imbalances with the flexor apparatus and intrinsic muscles, and joint contractures. This article will review the anatomy of the extensor mechanism and then will outline by location, the various clinical pictures that are secondary to chronic tendon injury. The clinical presentation of these injuries can be highly variable but their symptomatology and treatment are very specific. Of the possible therapeutic strategies for chronic mallet finger with or without associated swan-neck deformity, chronic boutonniere deformity, chronic sagittal band injuries, old ruptures on the dorsum of the wrist and traumatic defects in multiple tissues, conservative treatment is often the main element. Secondary surgical repair is not free of complications, and the results are often lacking. Rehabilitation and orthotic bracing are an integral part of the management of these injuries, no matter which treatment method is being considered. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Cardiac transcriptional response to acute and chronic angiotensin II treatments.

PubMed

Larkin, Jennie E; Frank, Bryan C; Gaspard, Renee M; Duka, Irena; Gavras, Haralambos; Quackenbush, John

2004-07-08

Exposure of experimental animals to increased angiotensin II (ANG II) induces hypertension associated with cardiac hypertrophy, inflammation, and myocardial necrosis and fibrosis. Some of the most effective antihypertensive treatments are those that antagonize ANG II. We investigated cardiac gene expression in response to acute (24 h) and chronic (14 day) infusion of ANG II in mice; 24-h treatment induces hypertension, and 14-day treatment induces hypertension and extensive cardiac hypertrophy and necrosis. For genes differentially expressed in response to ANG II treatment, we tested for significant regulation of pathways, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Microarray Pathway Profiler (GenMAPP) databases, as well as functional classes based on Gene Ontology (GO) terms. Both acute and chronic ANG II treatments resulted in decreased expression of mitochondrial metabolic genes, notably those for the electron transport chain and Krebs-TCA cycle; chronic ANG II treatment also resulted in decreased expression of genes involved in fatty acid metabolism. In contrast, genes involved in protein translation and ribosomal activity increased expression following both acute and chronic ANG II treatments. Some classes of genes showed differential response between acute and chronic ANG II treatments. Acute treatment increased expression of genes involved in oxidative stress and amino acid metabolism, whereas chronic treatments increased cytoskeletal and extracellular matrix genes, second messenger cascades responsive to ANG II, and amyloidosis genes. Although a functional linkage between Alzheimer disease, hypertension, and high cholesterol has been previously documented in studies of brain tissue, this is the first demonstration of induction of Alzheimer disease pathways by hypertension in heart tissue. This study provides the most comprehensive available survey of gene expression changes in response to acute and chronic ANG II treatment, verifying results from disparate studies, and suggests mechanisms that provide novel insight into the etiology of hypertensive heart disease and possible therapeutic interventions that may help to mitigate its effects.

Optimizing Patient Treatment Decisions in an Era of Rapid Technological Advances: The Case of Hepatitis C Treatment

PubMed Central

Liu, Shan; Goldhaber-Fiebert, Jeremy D.; Brandeau, Margaret L.

2015-01-01

How long should a patient with a treatable chronic disease wait for more effective treatments before accepting the best available treatment? We develop a framework to guide optimal treatment decisions for a deteriorating chronic disease when treatment technologies are improving over time. We formulate an optimal stopping problem using a discrete-time, finite-horizon Markov decision process. The goal is to maximize a patient’s quality-adjusted life expectancy. We derive structural properties of the model and analytically solve a three-period treatment decision problem. We illustrate the model with the example of treatment for chronic hepatitis C virus (HCV). Chronic HCV affects 3–4 million Americans and has been historically difficult to treat, but increasingly effective treatments have been commercialized in the past few years. We show that the optimal treatment decision is more likely to be to accept currently available treatment—despite expectations for future treatment improvement—for patients who have high-risk history, who are older, or who have more comorbidities. Insights from this study can guide HCV treatment decisions for individual patients. More broadly, our model can guide treatment decisions for curable chronic diseases by finding the optimal treatment policy for individual patients in a heterogeneous population. PMID:26188961

General Information about Chronic Lymphocytic Leukemia

MedlinePlus

... Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Chronic Myelogenous Leukemia

MedlinePlus

... Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

PubMed

Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

2017-01-01

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Pain Volatility and Prescription Opioid Addiction Treatment Outcomes in Patients with Chronic Pain

PubMed Central

Worley, Matthew J.; Heinzerling, Keith G.; Shoptaw, Steven; Ling, Walter

2015-01-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (N = 149) who received buprenorphine-naloxone (BUP-NLX) and counseling for 12 weeks in an outpatient, multi-site clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least two of the previous three weeks. Pain severity significantly declined over time during treatment (b = − 0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (OR = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A one standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP-NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk for returning to opioid use by the conclusion of an intensive treatment with BUP-NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

PubMed

Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

2015-12-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Effect of Depression Treatment on Chronic Pain Outcomes

PubMed Central

Teh, Carrie Farmer; Zaslavsky, Alan; Reynolds, Charles F.; Cleary, Paul D.

2011-01-01

Objective People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. We examined the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression Methods Propensity score weighted analyses using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems were used to examine the effect of (1) any depression treatment and (2) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of work days missed. Analyses were limited to those who met CIDI-SF criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n=553). Results Receiving any depression treatment was associated with higher scores on the mental component summary of the MOS SF-12, indicating better mental health (difference = 2.65 points, p=0.002) and less interference of pain on work (OR=0.57, p=0.02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Conclusions Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this Decade of Pain Control and Research to improve care for chronic pain sufferers. PMID:19875633

Effect of depression treatment on chronic pain outcomes.

PubMed

Teh, Carrie Farmer; Zaslavsky, Alan M; Reynolds, Charles F; Cleary, Paul D

2010-01-01

To examine the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression. People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. Propensity score-weighted analyses, using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems, were used to examine the effect of a) any depression treatment and b) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of workdays missed. Analyses were limited to those who met Composite International Diagnostic Interview Short-Form criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n = 553). Receiving any depression treatment was associated with higher scores on the mental component summary of the Medical Outcomes Study Short Form-12, indicating better mental health (difference = 2.65 points, p = .002) and less interference of pain on work (odds ratio = 0.57, p = .02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this decade of pain control and research to improve care for chronic pain sufferers.

Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia.

PubMed

Gofshteyn, Jacqueline; Cárdenas, Ana María; Bearden, David

2016-11-01

Enterovirus may result in a devastating chronic encephalitis in immunocompromised patients, particularly in patients with X-linked agammaglobulinemia. Prognosis for patients with chronic enterovirus encephalitis is poor, almost invariably resulting in mortality without specific treatment. There are currently no approved antiviral agents for enterovirus, but the antidepressant drug fluoxetine has been identified through library-based compound screening as a potential anti-enteroviral agent in vitro. However, use of fluoxetine has not previously been studied in humans with enteroviral disease. A five year old boy with X-linked agammaglobulinemia presented with progressive neurological deterioration and was found to have chronic enterovirus encephalitis by brain biopsy. He failed to respond to standard treatment with high dose intravenous immunoglobulin, but showed stabilization and improvement following treatment with fluoxetine. This is the first report to describe the use of fluoxetine as a potential therapy for chronic enterovirus infection. Further investigation of fluoxetine as a treatment option for chronic enterovirus encephalitis is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Non-arrhythmic therapy of ventricular tachyarrhythmias and sudden cardiac death after acute myocardial infarction.

PubMed

Schweitzer, P

2006-12-01

The management of ventricular tachyarrhythmias and prevention of sudden cardiac death after acute myocardial infarction (AMI) underwent important evolution. In the CAST study, encanaide and other antiarrhythmic drugs were not only ineffective but also increased mortality after myocardial infarction. Amiodarone had some beneficial effect on arrhythmic events without improving survival, and ICDs failed to improve outcome early after AMI. In comparison, short and long term survival benefits of beta blockers, angiotensine converting enzyme inhibitors and aldosterone antagonists after AMI is well established. This review discusses the role of non-arrhythmic therapy in the prevention of ventricular tachyarrhythmia's and sudden cardiac death after AMI.

[Clinical practice of systemic lysis in prehospital resuscitation. Success and complication rates].

PubMed

Everding, S; Römer, S; Bohn, A; Holz, E; Lieder, F; Baumgart, P; Loyen, M; Waltenberger, J; Lebiedz, P

2015-09-01

Systemic thrombolysis was introduced as the sole prehospital treatment option in patients with cardiac arrest in the setting of acute myocardial ischemia or pulmonary embolism; however, it remains the subject of discussion. A total of 194 patients with sudden prehospital cardiac arrest were included in this retrospective case control study. Of these patients, 96 in whom circulatory arrest due to cardiac disease (pulmonary artery embolism or myocardial ischemia) was suspected underwent thrombolytic treatment and were compared to the remaining 98 patients that did not undergo thrombolytic therapy. In addition to the circumstances of circulatory arrest, the course and success of resuscitation, as well as in-hospital course (including bleeding complications), overall survival and neurological outcomes were compared. There were no significant differences between patients with or without thrombolysis in terms of the circumstances of cardiac arrest. Patients that received thrombolytic treatment were significantly younger and were more frequently treated with anticoagulants, platelet aggregation inhibitors and amiodarone. They also received higher doses of epinephrine and arrived at hospital under ongoing resuscitation significantly more frequently. A trend toward more prehospital return of spontaneous circulation (ROSC) following thrombolytic treatment was seen in the entire cohort. However, patients pre-treated with acetylsalicylic acid and heparin did not show better prehospital ROSC rates as a result of additional thrombolytic therapy. Significant differences in terms of bleeding complications or the need for blood transfusion could not be seen due to the small number of patients. The indication for systemic thrombolysis in the context of prehospital resuscitation should remain restricted to patients with clear symptoms of acute pulmonary embolism or recurrent episodes of ventricular fibrillation in the setting of acute myocardial infarction. Due to a lack of evidence, systemic thrombolysis should not be used as a treatment of last resort in younger patients with persistent ventricular fibrillation.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

The Relationship Between Posttraumatic Stress Disorder and Chronic Pain in People Seeking Treatment for Chronic Pain: The Mediating Role of Psychological Flexibility.

PubMed

Åkerblom, Sophia; Perrin, Sean; Rivano Fischer, Marcelo; McCracken, Lance M

2018-06-01

The symptoms of posttraumatic stress disorder (PTSD) and chronic pain are thought to interact to increase the severity and impact of both conditions, but the mechanisms by which they interact remain unclear. This study examines the relationship between PTSD and chronic pain and whether indices of Psychological Flexibility mediate the relationship between these 2 conditions. Standardized self-report measures of PTSD, pain severity, pain interference, depression, and psychological flexibility (pain-related acceptance, committed action, cognitive fusion, and values-based action) were obtained from 315 people seeking treatment for chronic pain who also reported at least 1 traumatic experience. People seeking treatment for chronic pain and reporting symptoms consistent with a current diagnosis of PTSD had significantly higher levels of pain severity, pain interference, depression, and cognitive fusion and lower levels of pain-related acceptance and committed action than those reporting symptoms below the diagnostic threshold for PTSD. Pain-related acceptance, committed action, cognitive fusion, and depression mediated the relationship between PTSD and pain severity/interference, with pain-related acceptance being the strongest mediator from the Psychological Flexibility model. Processes from the Psychological Flexibility model were identified as mediators of the relationship between PTSD and chronic pain in people seeking treatment for chronic pain. The Psychological Flexibility model may be useful as an overarching model to help understand the relationship between PTSD and chronic pain. It is possible that targeting pain-related acceptance, committed action, and cognitive fusion (among other processes) in the treatment of chronic pain may produce corresponding improvements in comorbid symptoms of PTSD when these are present and may reduce impacts of PTSD on outcomes of chronic pain. Conversely, targeting of these processes in the treatment of PTSD may produce similar improvements for symptoms of chronic pain. Further research to evaluate these possibilities is needed.

Computers in the treatment of chronic aphasia.

PubMed

Katz, Richard C

2010-02-01

Computers and related technology can increase the amount of treatment received by adults with chronic aphasia. Computers used in treatment, however, are only valuable to the patient if the intervention is efficacious. Real and potential applications of computer technology are discussed in the context of three roles of computerized aphasia treatment for adults with chronic aphasia. Pertinent studies regarding Phases 1 and 2 are briefly described. The only Phase 3 study of efficacy of computerized aphasia treatment is more fully described and its implications discussed.

Development of a Guided Internet-based Psycho-education Intervention Using Cognitive Behavioral Therapy and Self-Management for Individuals with Chronic Pain.

PubMed

Perry, Jennifer; VanDenKerkhof, Elizabeth G; Wilson, Rosemary; Tripp, Dean A

2017-04-01

Evidence-based chronic pain treatment includes nonpharmacologic therapies. When addressing barriers to treatment, there is a need to deliver these therapies in a way that is accessible to all individuals who may benefit. To develop a guided Internet-based intervention for individuals with chronic pain, program content and sequence of evidence-based treatments for chronic pain, traditionally delivered via in-person sessions, were identified to be adapted for Internet delivery. With consideration to historical barriers to treatment, and through use of a concept map, therapeutic components and educational material were situated, in an ordered sequence, into six modules. An Internet-based chronic pain intervention was constructed to improve access to evidence-based chronic pain therapies. Research using this intervention, in the form of a pilot study for intervention refinement, was conducted, and a large-scale study to assess effectiveness is necessary prior to implementation. As clients may face barriers to multimodal treatment for chronic pain, nurses could introduce components of education, cognitive behavioral therapy and self-management to clients and prepare them for the "work" of managing chronic pain, through use of this Internet-based intervention. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Chronic pelvic pain.

PubMed

Stein, Sharon L

2013-12-01

Chronic pelvic pain is pain lasting longer than 6 months and is estimated to occur in 15% of women. Causes of pelvic pain include disorders of gynecologic, urologic, gastroenterologic, and musculoskeletal systems. The multidisciplinary nature of chronic pelvic pain may complicate diagnosis and treatment. Treatments vary by cause but may include medicinal, neuroablative, and surgical treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study.

PubMed

Mattos Júnior, Francisco Moreira; Mattos, Rafael Villanova; Teixeira, Manoel Jacobsen; Siqueira, Silvia Regina Dowgan Tesseroli de; Siqueira, Jose Tadeu Tesseroli de

2015-07-01

The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001) and in its intensity (p < 0.001). Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

Chronic proctalgia and chronic pelvic pain syndromes: New etiologic insights and treatment options

PubMed Central

Chiarioni, Giuseppe; Asteria, Corrado; Whitehead, William E

2011-01-01

This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs: chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing: A recently published large randomized, controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders. PMID:22110274

State of the art in biobehavioral approaches to the management of chronic pain in childhood

PubMed Central

Simons, Laura E; Basch, Molly C

2016-01-01

Chronic pain in childhood is prevalent, persistent and significantly impactful on most domains of life. The chronic pain experience occurs within a complex biopsychosocial framework, with particular emphasis on the social context. Currently, psychological treatments involve a cognitive–behavioral therapy treatment plan, providing some combination of psychoeducation, self-regulation training, maladaptive cognition identification, behavioral exposure and parent involvement. New treatment areas are emerging, such as group- and internet-based cognitive–behavioral therapy, motivational interviewing, comorbid obesity intervention and intensive multidisciplinary rehabilitation. Preliminary studies of emerging treatments demonstrate encouraging results; however, treatment effectiveness hinges on accurate matching of patient to treatment modality. Overall, the current direction of the field promises many innovative breakthroughs to ameliorate suffering in youth with chronic pain. PMID:26678858

Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

PubMed

Jindracek, Lauren; Stark, Jennifer

2017-01-01

Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

Association Between Facility-Level Utilization of Non-pharmacologic Chronic Pain Treatment and Subsequent Initiation of Long-Term Opioid Therapy.

PubMed

Carey, Evan P; Nolan, Charlotte; Kerns, Robert D; Ho, P Michael; Frank, Joseph W

2018-05-01

Expert guidelines recommend non-pharmacologic treatments and non-opioid medications for chronic pain and recommend against initiating long-term opioid therapy (LTOT). We examined whether veterans with incident chronic pain receiving care at facilities with greater utilization of non-pharmacologic treatments and non-opioid medications are less likely to initiate LTOT. Retrospective cohort study PARTICIPANTS: Veterans receiving primary care from a Veterans Health Administration facility with incident chronic pain between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent" chronic pain. The independent variable was facility-level utilization of pain-related treatment modalities (non-pharmacologic, non-opioid medications, LTOT) in the prior calendar year. The dependent variable was patient-level initiation of LTOT (≥ 90 days within 365 days) in the subsequent year, adjusting for patient characteristics. Among 1,094,569 veterans with incident chronic pain from 2010 to 2015, there was wide facility-level variation in utilization of 10 pain-related treatment modalities, including initiation of LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with greater utilization of non-pharmacologic treatments were less likely to initiate LTOT in the year following incident chronic pain. Conversely, veterans receiving care at facilities with greater non-opioid and opioid medication utilization were more likely to initiate LTOT; this association was strongest for past year facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in prior calendar year). Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain. Further studies should seek to understand facility-level variation in chronic pain care and to identify facility-level utilization patterns that are associated with improved patient outcomes.

Psychological Neuromodulatory Treatments for Young People with Chronic Pain

PubMed Central

Miró, Jordi; Castarlenas, Elena; de la Vega, Rocío; Roy, Rubén; Solé, Ester; Tomé-Pires, Catarina; Jensen, Mark P.

2016-01-01

The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments—neurofeedback, meditation and hypnosis—when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function), at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1) providing an empirical basis for better patient-treatment matching; and (2) identifying specific mechanisms that could be targeted with treatment. PMID:27929419

Transrectal microwave thermotherapy causing a short-time influence on sperm quality in Chinese chronic nonbacterial prostatitis patients.

PubMed

Jin, Jia-Xin; Wang, Han-Zhang; Zhai, Zheng-Xing; Ma, Bao-Liang; Li, Qin-Fang; Xiao, Nan; Wang, Zhi-Ping; Rodriguez, Ronald

2017-01-01

Chronic prostatitis can affect the sperm's quality. Previous studies have shown that transrectal microwave thermotherapy (TRMT) results in symptomatic relief in patients with chronic prostatitis, but the effects on sperm have not been carefully investigated. This study evaluates the impact of TRMT on the relief or decrease of symptoms and quality of sperm when used to treat patients with chronic nonbacterial prostatitis. Sixty patients were enrolled in the study. TRMT treatment was administered over 5 days, 1 h per day. Semen examination was carried out pretreatment and immediately at the conclusion of the 5-day treatment. Also, it was repeated 1 month, 3 months, and 6 months later. The treatment's symptom relief efficacy was evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). After the treatment, the overall NIH-CPSI scores were lower compared to those of pretreatment. In addition, the white blood cells and lecithin in expressed prostatic secretion were normal after the treatment. The sperm count was decreased by 23.8% 3 months after the treatment, sperm motility was reduced by 10.3% immediately after treatment, and sperm deformity was increased by 17.2%. The sperm volume and PH were not affected. However, the sperm quality recovered after treatment and the malformation rate was also lower at 6 months after treatment. TRMT is a favorable and safe treatment option for patients with nonbacterial chronic prostatitis. It could relieve the patient's symptoms and impact on sperm quality in the short-term.

Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension.

PubMed Central

Lijnen, P; Fagard, R; Staessen, J; Amery, A

1981-01-01

1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the maximum level reached after 1 week. 3 A significant (P less than 0.01) correlation (r = 0.74) between changes in plasma angiotensin II and renin activity provoked by chronic treatment for 3 months with hydrochlorothiazide and tienilic acid was found. 4 The increase in plasma aldosterone during chronic treatment with hydrochlorothiazide and tienilic acid (1000 mg) is related (r = 0.68; P less than 0.01) to the rise in plasma angiotensin II. PMID:7028060

[RECOMMENDATION FOR EVALUATION AND TREATMENT OF CHRONIC URTICARIA - THE ISRAELI ASSOCIATION FOR ALLERGY AND CLINICAL IMMUNOLOGY].

PubMed

Levin Agmon, Nancy; Kessel, Aharon; Maoz Segal, Ramit; Rottem, Menachem; Tal, Yuval; Confino-Cohen, Ronit; Tobi, Elias

2017-06-01

Chronic urticaria is a disease manifested by a pruritic rash lasting longer than 6 weeks that may severely affect quality of life and daily function. Chronic urticaria can be further divided into chronic spontaneous urticaria which appears without a trigger and chronic inducible urticaria which evolves following distinct physical triggers. These two clinical manifestations could coexist in the same patient. The pathogenesis of chronic urticaria is not fully elucidated, although it is considered an autoimmune disease in at least 50% patients that produce auto- IgG antibodies targeted against the high affinity Fc receptor and to a lesser extent against IgE itself. Auto-antibodies associated with different autoimmune diseases can be detected such as those directed at thyroid proteins. Urticaria tends to spontaneously resolve in 50% of patients within the first year while others will suffer from it for a much longer period of time. The treatment of chronic urticaria has dramatically progressed in the last decade, enabling reduction of systemic corticosteroid use which has been the cornerstone of treatment in the past. The recommended treatment for chronic urticaria is currently based on a stepwise approach that enables achieving disease control with a reasonably good quality of life. The first step of the treatment ladder consists of selective, new generation, anti-H1 histamine blockers, which do not cross the blood brain barrier, starting from the recommended dose (first line) and increasing up to four-fold (second line). The third line of treatment is the addition of immune modulators such as leukotriene receptor blockers (Singulair), anti-IgE biological therapy (Xolair), or cyclosporine. In this review we present the updates and considerations arising during evaluation and treatment of chronic urticaria. The need for specific tests, immunologist/allergologist evaluation, as well as treatment modalities taking into consideration the large body of evidence that has accumulated in the last few years, the new international guidelines as well as their application in Israel have been addressed.

Evidence-based guidelines for the chiropractic treatment of adults with neck pain.

PubMed

Bryans, Roland; Decina, Philip; Descarreaux, Martin; Duranleau, Mireille; Marcoux, Henri; Potter, Brock; Ruegg, Richard P; Shaw, Lynn; Watkin, Robert; White, Eleanor

2014-01-01

The purpose of this study was to develop evidence-based treatment recommendations for the treatment of nonspecific (mechanical) neck pain in adults. Systematic literature searches of controlled clinical trials published through December 2011 relevant to chiropractic practice were conducted using the databases MEDLINE, EMBASE, EMCARE, Index to Chiropractic Literature, and the Cochrane Library. The number, quality, and consistency of findings were considered to assign an overall strength of evidence (strong, moderate, weak, or conflicting) and to formulate treatment recommendations. Forty-one randomized controlled trials meeting the inclusion criteria and scoring a low risk of bias were used to develop 11 treatment recommendations. Strong recommendations were made for the treatment of chronic neck pain with manipulation, manual therapy, and exercise in combination with other modalities. Strong recommendations were also made for the treatment of chronic neck pain with stretching, strengthening, and endurance exercises alone. Moderate recommendations were made for the treatment of acute neck pain with manipulation and mobilization in combination with other modalities. Moderate recommendations were made for the treatment of chronic neck pain with mobilization as well as massage in combination with other therapies. A weak recommendation was made for the treatment of acute neck pain with exercise alone and the treatment of chronic neck pain with manipulation alone. Thoracic manipulation and trigger point therapy could not be recommended for the treatment of acute neck pain. Transcutaneous nerve stimulation, thoracic manipulation, laser, and traction could not be recommended for the treatment of chronic neck pain. Interventions commonly used in chiropractic care improve outcomes for the treatment of acute and chronic neck pain. Increased benefit has been shown in several instances where a multimodal approach to neck pain has been used. © 2014. Published by National University of Health Sciences All rights reserved.

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

PubMed

Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

2016-08-01

To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Evaluation of treatment with carboxymethylcellulose on chronic venous ulcers*

PubMed Central

Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli

2016-01-01

BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773

Visually induced analgesia during massage treatment in chronic back pain patients.

PubMed

Löffler, A; Trojan, J; Zieglgänsberger, W; Diers, M

2017-11-01

Previous findings suggest that watching sites of experimental and chronic pain can exert an analgesic effect. Our present study investigates whether watching one's back during massage increases the analgesic effect of this treatment in chronic back pain patients. Twenty patients with chronic back pain were treated with a conventional massage therapy. During this treatment, patients received a real-time video feedback of their own back. Watching a neutral object, a video of another person of the same sex being massaged, a picture of the own back, and keeping one's eyes closed were used as controls. These conditions were presented in randomized order on five separate days. All conditions yielded significant decreases in habitual pain intensity. The effect of real-time video feedback of the own back on massage treatment was the strongest and differed significantly from the effect of watching a neutral object, but not from the other control conditions, which may have induced slight effects of their own. Repeated real-time video feedback may be useful during massage treatment of chronic pain. This study shows that inducing visual induced analgesia during massage treatment can be helpful in alleviating chronic pain. © 2017 European Pain Federation - EFIC®.

Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

PubMed

Łaski, Dariusz; Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

2018-03-01

Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis

PubMed Central

Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

2018-01-01

Introduction Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland – NFZ) and the national insurance system (Poland – ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. Aim The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung’s duct within the Polish health care system. Results In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. Conclusions From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months. PMID:29643954

Involvement of the K+-Cl- co-transporter KCC2 in the sensitization to morphine-induced hyperlocomotion under chronic treatment with zolpidem in the mesolimbic system.

PubMed

Shibasaki, Masahiro; Masukawa, Daiki; Ishii, Kazunori; Yamagishi, Yui; Mori, Tomohisa; Suzuki, Tsutomu

2013-06-01

Benzodiazepines are commonly used as sedatives, sleeping aids, and anti-anxiety drugs. However, chronic treatment with benzodiazepines is known to induce dependence, which is considered related to neuroplastic changes in the mesolimbic system. This study investigated the involvement of K(+) -Cl(-) co-transporter 2 (KCC2) in the sensitization to morphine-induced hyperlocomotion after chronic treatment with zolpidem [a selective agonist of γ-aminobutyric acid A-type receptor (GABAA R) α1 subunit]. In this study, chronic treatment with zolpidem enhanced morphine-induced hyperlocomotion, which is accompanied by the up-regulation of KCC2 in the limbic forebrain. We also found that chronic treatment with zolpidem induced the down-regulation of protein phosphatase-1 (PP-1) as well as the up-regulation of phosphorylated protein kinase C γ (pPKCγ). Furthermore, PP-1 directly associated with KCC2 and pPKCγ, whereas pPKCγ did not associate with KCC2. On the other hand, pre-treatment with furosemide (a KCC2 inhibitor) suppressed the enhancing effects of zolpidem on morphine-induced hyperlocomotion. These results suggest that the mesolimbic dopaminergic system could be amenable to neuroplastic change through a pPKCγ-PP-1-KCC2 pathway by chronic treatment with zolpidem. © 2013 International Society for Neurochemistry.

Effects of chronic fluvoxamine on ethanol- and food-maintained behaviors

PubMed Central

Ginsburg, Brett C.; Lamb, R.J.

2011-01-01

Acute treatment with fluvoxamine reduces responding for ethanol more than responding for food. However, pharmacotherapy for alcoholism is likely to require chronic treatment. These experiments were performed to assess the effects of chronic fluvoxamine on ethanol- and food-maintained behaviors. Effects of chronic fluvoxamine (10 and 17.8 mg/kg/day × 30 days) on ethanol- and food-maintained responding were compared to responding during saline treatment in four Sprague-Dawley rats responding for ethanol and food under a multiple fixed-ratio 5, fixed-ratio 5 schedule. In two subjects, chronic fluvoxamine reduced ethanol-maintained responding more than food-maintained responding; however this effect was transient. In another subject, treatment persistently decreased food-maintained responding relative to ethanol-maintained responding. Finally, in one subject, fluvoxamine nonspecifically disrupted responding for food and ethanol. Similar to results in humans, outbred Sprague-Dawley rats had differential responses to chronic fluvoxamine. The effect was transient in rats that responded favorably (greater reduction of ethanol relative to food responding), while response reductions persisted throughout treatment in rats that responded unfavorably (greater reduction of food relative to ethanol or nonspecific reductions). PMID:16647721

New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

PubMed

Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi

2013-12-01

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Diagnosis and management of neuropathic pain: a balanced approach to treatment.

PubMed

Nicholson, Bruce D

2003-12-01

To provide nurse practitioners with a conceptual framework from which to diagnose and manage chronic neuropathic pain, specifically postherpetic neuralgia (PHN). A current review of the available treatment options for the management of neuropathic pain and PHN is provided. A comprehensive literature review was conducted. Clinical articles, meta-analyses, and reviews were selected for their relevance to the diagnosis and management of chronic neuropathic pain and PHN. Managing patients with chronic neuropathic pain is a common clinical challenge due to variability in individual symptoms, mechanisms, and treatment responses. In patients with PHN, a balanced treatment approach focusing on efficacy, safety, and tolerability is recommended. With appropriate treatment, most patients are able to achieve clinically significant relief from neuropathic pain. Diagnosis and management of neuropathic pain syndromes is challenging. Because of the complexity of chronic pain, successful long-term treatment can be especially difficult (Nicholson, 2003b). While most acute pain is nociceptive (i.e., a response to noxious stimuli), chronic pain can be nociceptive, neuropathic, or of mixed origin. PHN is a chronic pain syndrome that can last for years, causing physical and social disability and psychological distress (Kanazi, 2000). Despite major recent advances in the treatment of PHN, many patients remain refractory to current therapy (Dworkin, 2003). For practicing clinicians, including nurse practitioners, viewing pain as a disease rather than a symptom is the first step towards its successful management. Understanding the pathophysiology of chronic pain and emerging treatment paradigms for the management of neuropathic pain and PHN is critical to optimal care.

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

PubMed

Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

2016-05-01

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

New perspectives for chronic pain treatment: a patent review (2010-2016).

PubMed

Pina, Lícia T S; Gouveia, Daniele N; Costa, Janara S; Quintans, Jullyana S S; Quintans-Júnior, Lucindo J; Barreto, Rosana S S; Guimarães, Adriana G

2017-07-01

Chronic pain is a major problem of public health worldwide and is responsible for the increase in health costs. The therapeutic options available in the market for the treatment of chronic pain are often rather ineffective due to; the high number of adverse reactions, tolerance and dependence, reducing the quality of life, pharmacotherapy adherence and functional capacity. Hence, several studies have been conducted in the search for new treatment alternatives for chronic pain syndromes. Areas covered: This review brings together the therapeutic patents published over the past six years reporting the discovery of new drugs for the treatment of chronic pain, based on the perspective that these compounds are candidates for the management of chronic pain conditions. Expert opinion: Over the past 6 years, several pharmaceutical companies, as well as universities and researchers, have synthesized a series of compounds, which have been shown to be effective in controlling chronic pain in preclinical studies. These findings nurture the hope of discovering new therapeutic options for chronic pain. However, such studies are in early stages and there is a long and hard path to be followed until these compounds can become chemical entities available to the public.

Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

USDA-ARS?s Scientific Manuscript database

Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

Endoscopic treatment of chronic radiation proctopathy.

PubMed

Wilson, Sydney A; Rex, Douglas K

2006-09-01

Chronic radiation proctopathy is a complication of pelvic radiation therapy. The acute phase of radiation injury to the rectum occurs during or up to 3 months following radiation. Acute radiation injury can continue into a chronic phase or chronic radiation proctopathy may develop after a latent period of several months or years. Symptoms associated with the condition include diarrhea, rectal pain, bleeding, tenesmus, and stricture formation. Of the various symptoms, only bleeding from radiation-induced telangiectasias is amenable to endoscopic therapy. This paper summarizes the findings of experts in the field on endoscopic treatment of bleeding from chronic radiation proctopathy. Medical management is generally ineffective in controlling bleeding from chronic radiation proctopathy. Surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including formalin, neodymium/yttrium aluminum garnet, argon and potassium titanyl phosphate laser treatments, as well as argon plasma coagulation. Argon plasma coagulation presents an effective, efficient, inexpensive and reasonably safe noncontact method for destruction of radiation telangiectasias. Based on currently available data and trends, argon plasma coagulation is the favored treatment for bleeding from chronic radiation proctopathy.

Atrial Fibrillation in Eight New World Camelids.

PubMed

Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

2016-01-01

There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Chronic Achilles tendinopathy: a prospective randomized study comparing the therapeutic effect of eccentric training, the AirHeel brace, and a combination of both.

PubMed

Petersen, Wolf; Welp, Robert; Rosenbaum, Dieter

2007-10-01

Previous studies have shown that eccentric training has a positive effect on chronic Achilles tendinopathy. A new strategy for the treatment of chronic Achilles tendinopathy is the AirHeel brace. AirHeel brace treatment improves the clinical outcome of patients with chronic Achilles tendinopathy. The combination of the AirHeel brace and an eccentric training program has a synergistic effect. Randomized controlled clinical trial; Level of evidence, 1. One hundred patients were randomly assigned to 1 of 3 treatment groups: (1) eccentric training, (2) AirHeel brace, and (3) combination of eccentric training and AirHeel brace. Patients were evaluated at 6, 12, and 54 weeks after the beginning of the treatment protocol with ultrasonography, visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) ankle score, and Short Form-36 (SF-36). The VAS score for pain, AOFAS score, and SF-36 improved significantly in all 3 groups at all 3 follow-up examinations. At the 3 time points (6 weeks, 12 weeks, and 54 weeks) of follow-up, there was no significant difference between all 3 treatment groups. In all 3 groups, there was no significant difference in tendon thickness after treatment. The AirHeel brace is as effective as eccentric training in the treatment of chronic Achilles tendinopathy. There is no synergistic effect when both treatment strategies are combined. The AirHeel brace is an alternative treatment option for chronic Achilles tendinopathy.

[Efficiency of multidisciplinary treatment of chronic pain with locomotor disability].

PubMed

Collado Cruz, A; Torres i Mata, X; Arias i Gassol, A; Cerdà Gabaroi, D; Vilarrasa, R; Valdés Miyar, M; Muñoz-Gómez, J

2001-10-13

Disabling chronic pain is especially devastating among working population and, in many cases, it does not respond to conventional therapies. In chronic pain, the importance of psychosocial and occupational factors, in addition to biological ones, has prompted the development of successful multidisciplinary treatment programmes in various countries. We assessed the outcome of a multidisciplinary therapeutic program for work-disabled selected patients with chronic pain refractory to conventional treatment. The study included 70 patients (58 women, mean age [SD]: 42 [9]years) with chronic pain and sick leave (mean [SD]: 7 [4] months of work disability) diagnosed with fibromyalgia (51%), chronic low back pain (16%), regional myofascial pain (15%), cervicocraneal syndrome (3%), anquilosing spondylitis (3%), and other conditions(12%). All patients had received previous pharmacological treatment,physical therapy and/or other measures (surgery in 12% cases)without improvement. All patients underwent an intensive multidisciplinary treatment of 4 weeks' duration including medical techniques for pain control, cognitive-behavioural therapy, physical therapy,and occupational therapy. Average follow-up was 10 (4) months(1-24 months) post-discharge. Significant improvements were observed with regard to all relevant variables, as reflected in pre and post-discharge measures: pain(Visual-Analogue Scale 1-10 cm): 7.4 (1.5) versus 3.2 (2) (p <0.01); anxiety (HARS), 19 (7) versus 14 (8) (p < 0.01); depression(BDI), 16 (8) versus 10 (8) (p < 0.01); functional ability(HAQ), 1.6 (0.4) versus 0.6 (0.5) (p < 0.001). At discharge,73% of patients returned to work. In addition, 69% of treated patients maintained the acquired improvement and their employment status at the end of follow-up. Multidisciplinary treatment of chronic pain with special attention to work return is useful for selected patients with a disabling chronic pain syndrome refractory to conventional treatment.

Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

PubMed

Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru

2016-02-01

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

[Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

PubMed

Kat'uchová, Jana; Radonak, Jozef

2011-01-01

Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

PubMed

Spasojevic, Natasa; Jovanovic, Predrag; Dronjak, Sladjana

2015-03-01

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

PubMed

Zicha, Josef; Dobesová, Zdenka; Kunes, Jaroslav

2006-12-01

Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

PubMed Central

Tadokoro, Shigenori; Okamura, Naoe; Sekine, Yoshimoto; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi

2012-01-01

Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. PMID:21402722

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria.

PubMed

Wang, Sheng-Huei; Tang, Shih-En; Li, Yu-Huei; Wei, Kuang-Yu; Chang, Chan-Yuan

2017-01-01

Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

Migraines in Women: Current Evidence for Management of Episodic and Chronic Migraines.

PubMed

Deneris, Angela; Rosati Allen, Peggy; Hart Hayes, Emily; Latendresse, Gwen

2017-05-01

Migraine headache is a disabling brain disorder that affects millions of women in the United States. Many migraine sufferers are undertreated. Both inadequate treatment and overuse of abortive migraine medication can contribute to progression from episodic to chronic migraine disorders. A significant number of migraine headaches or severity of episodic migraine headaches warrants treatment with prophylactic medications for prevention. This clinical update reviews the pathophysiology and diagnosis of migraine headaches in women, discusses the efficacy of abortive and chronic pharmacologic treatment, and examines strategies to prevent progression from episodic migraine to chronic migraine. A discussion of treatment during pregnancy and lactation is included. © 2017 by the American College of Nurse-Midwives.

Chronic daily headache in children and adolescents: science and conjecture.

PubMed

Connelly, Mark; Bickel, Jennifer

2013-01-01

SUMMARY Chronic daily headache comprises a group of headache disorders in which headaches occur almost daily or continuously over several months. Although chronic daily headache is one of the most common chronic pain disorders in pediatrics, data on pathophysiological mechanisms and relative efficacy of treatments remain sparse. In this review, we aim to provide contemporary information on classification, epidemiology, etiology and treatment of pediatric chronic daily headache based on extant empirical data when available, or general consensus in the field when not.

New developments in the pharmacotherapy of neuropathic chronic pelvic pain

PubMed Central

Carey, Erin T; As-Sanie, Sawsan

2016-01-01

Advancements in further understanding the pathophysiology of chronic pelvic pain syndromes continue to direct therapy. The mechanisms of chronic pelvic pain are often multifactorial and therefore require a multidisciplinary approach. The final treatment plan is often an accumulation of organ-specific treatment and chronic pain medications directed to the CNS and PNS. This article is a review of commonly used medications for chronic pelvic neuropathic pain disorders as well as an introduction to recent innovative developments in pain medicine. PMID:28116131

[Clinical and immunological assessment of Polyoxidonium and Tantum Verde efficiency by catarrhal gingivitis treatment in children with chronic gastroduodenitis].

PubMed

Kazarina, L N; Pursanova, A E

2014-01-01

The article presents findings allowing estimating effect of local application of polioxidonium and yantum verde in 101 children aged 12-17 with chronic catarrhal gingivitis and chronic gastroduodenitis. Statistically significant PMA indeх decrease (40.1±2.3% till 1.4±0.6% (р<0,001)) proved the above mentioned therapy scheme to be highly effective for treatment of chronic catarrhal gingivitis in children with chronic gastroduodenitis.

Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.

PubMed

Czaja, A J; Ludwig, J; Baggenstoss, A H; Wolf, A

1981-01-01

To assess the prognosis of patients with severe chronic hepatitis after histologic examination had shown an improvement to chronic persistent hepatitis, we followed 52 such patients regularly for 54 +/- 4 months after the cessation of corticosteroid therapy. In 24 patients, the condition deteriorated 7 +/- 1 months after therapy and required further treatment with prednisone. Histologic features of chronic active hepatitis, including bridging and multilobular necrosis, were documented in all 14 patients in whom biopsies were performed. In 20 of 24 patients, the disease responded to retreatment, but 13 again had relapses, and cirrhosis developed in two. Of 28 patients who remained asymptomatic for 48 +/- 6 months, 17 retained features of chronic persistent hepatitis, and nine had improvement to normal histologic features. Cirrhosis developed in two patients without clinical manifestations of active inflammation. Findings before and after treatment did not predict outcome. We conclude that severe chronic active hepatitis that has been treated with prednisone and converted to chronic persistent hepatitis will often and unpredictably deteriorate after treatment has been stopped. Cirrhosis develops rarely but may occur with or without clinically overt chronic active hepatitis.

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg.

PubMed

Giménez-Arnau, A; Izquierdo, I; Maurer, M

2009-09-01

According to the EAACI/GA(2)LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg. Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.

Surgical and endoscopic treatment of pain in chronic pancreatitis: a multidisciplinary update.

PubMed

Issa, Y; van Santvoort, H C; van Goor, H; Cahen, D L; Bruno, M J; Boermeester, M A

2013-01-01

Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to achieve long-term pain relief, control of the complications associated with the disease, and to restore the quality of life. Currently, a conservative step-up approach is often used for the treatment of pain; progression to severe and intractable pain is considered necessary before invasive treatment is considered. Recent studies, however, suggest that surgical intervention should not be considered only as last-resort treatment, since it can mitigate disease progression, achieve excellent pain control, and preserve pancreatic function. In this review, we present a state-of-the art overview of endoscopic and surgical treatment options for patients with painful chronic pancreatitis, and elaborate on the timing of surgery. Copyright © 2013 S. Karger AG, Basel.

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

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

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com; Wisialowski, Todd A.; Cremers, Thomas

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure ofmore » arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular safety and efficacy more adequately address therapeutic index ► Similar paradigms may exist with other centrally and peripherally acting drugs.« less

[Treatment motivation in patients with chronic cardiorenal syndrome].

PubMed

Efremova, E V; Shutov, A M; Borodulina, E O

2015-01-01

To study treatment motivation in patients with chronic heart failure (CHF) and in those with CHF concurrent with chronic kidney disease (CKD). A total of 203 patients (130 men and 73 women; mean age, 61.8±9.6 years) with CHF diagnosed and assessed in accordance with the National Guidelines of the All-Russian Research Society of Cardiology and the Heart Failure Society for the diagnosis and treatment of CHF (third edition, 2009) were examined. CKD was diagnosed according to the 2012 National Guidelines of the Research Nephrology Society of Russia. A group of patients with chronic cardiorenal syndrome (CRS) included those with CHF and CKD with a glomerular filtration rate (GFR) of <60 ml/min/1.73 m2. The clinical course of CHF, personality profile, and motivation for non-drug and drug treatments were assessed in patients with chronic CRS. CFR was 67.7±17.2 ml/min/1.73 m2; chronic CRS was observed in 89 (44%) patients. Psychological functioning assessment showed that the patients with chronic CRS as compared with those with CHF without CKD had high anxiety and maladaptive disease attitudes. CHF treatment motivation (compliance with lifestyle modification and medication) was proved inadequate and detected only in 31 (15.3%) patients with CHF regardless of the presence of CKD. The specific features of psychological functioning, which affected treatment motivation, were seen in patients with chronic CRS: those who were lowly motivated had a euphoric attitude towards their disease (p=0.03); those who were satisfactorily motivated showed an emotive accentuation of character (p=0.002). The presence of CKD aggravates the clinical course of CHF and negatively affects the psychological functioning of patients with CHF. The patients with chronic CRS are characterized by a low level of motivation for both drug and non-drug treatments, which should be taken into account when managing this cohort of patients.

Endoscopic versus surgical drainage treatment of calcific chronic pancreatitis.

PubMed

Jiang, Li; Ning, Deng; Cheng, Qi; Chen, Xiao-Ping

2018-04-21

Endoscopic therapy and surgery are both conventional treatments to remove pancreatic duct stones that developed during the natural course of chronic pancreatitis. However, few studies comparing the effect and safety between surgery drainage and endoscopic drainage (plus Extracorporeal Shock Wave Lithotripsy, ESWL).The aim of this study was to compare the benefits between endoscopic and surgical drainage of the pancreatic duct for patients with calcified chronic pancreatitis. A total of 86 patients were classified into endoscopic/ESWL (n = 40) or surgical (n = 46) treatment groups. The medical records of these patients were retrospectively analyzed. Pain recurrence and hospital stays were similar between the endoscopic/ESWL treatment and surgery group. However, endoscopic/ESWL treatment yielded significantly lower medical expense and less complications compared with the surgical treatment. In selective patients, endoscopic/ESWL treatment could achieve comparable efficacy to the surgical treatment. With lower medical expense and less complications, endoscopic/ESWL treatment would be much preferred to be the initial treatment of choice for patients with calcified chronic pancreatitis. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Comparative Effectiveness of Proactive Tobacco Treatment among Smokers with and without Chronic Lower Respiratory Disease.

PubMed

Melzer, Anne C; Clothier, Barbara A; Japuntich, Sandra J; Noorbaloochi, Siamak; Hammett, Patrick; Burgess, Diana J; Joseph, Anne M; Fu, Steven S

2018-03-01

Adults with chronic lower respiratory disease differ in their barriers to smoking cessation but also suffer from tobacco-related health concerns, which may motivate quit attempts. Few studies have examined differences in tobacco treatment response between smokers with and without chronic lower respiratory disease. We examined the effectiveness of a proactive outreach program for cessation among smokers with and without chronic lower respiratory disease. Subgroup analysis of the Veterans Victory over Tobacco Study, a pragmatic randomized controlled trial that demonstrated the effectiveness of proactive outreach and the choice of tobacco treatments compared with usual care. Smokers identified via the electronic medical record were proactively offered phone-based counseling and care coordination to receive medication from their Veterans Affairs providers or in-person care. We compared the response among those with and without an International Classification of Diseases, 9th Revision diagnosis of a chronic lower respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma). We used stratification by propensity scores to adjust for imbalanced covariates between groups with and without chronic lower respiratory disease within each treatment arm, using complete case analysis accounting for the stratified sampling by site. The study participants were predominantly older, white, male smokers. Overall, 19.6% had chronic lower respiratory disease. A total of 3,307 had outcome data with the following assignments to the intervention: proactive care: n = 1,272 without chronic lower respiratory disease, n = 301 with chronic lower respiratory disease; usual care: n = 1,387 without chronic lower respiratory disease, n = 347 with chronic lower respiratory disease. A total of 1,888 had both complete baseline and outcome data and were included in the primary analysis. In unadjusted analyses (n = 3,307), among individuals with chronic lower respiratory disease, 13.1% in the proactive group reported 6-month prolonged abstinence compared with 8.7% of those in the usual care group (odds ratio, 1.57; 95% confidence interval, 0.93-2.65). Among individuals without chronic lower respiratory disease, 13.1% quit in the proactive group compared with 11.0% in the usual care group (odds ratio, 1.22; 95% confidence interval, 0.95-1.55). In adjusted analyses (n = 1,888), the association between treatment arm and quit rate varied by the presence of chronic lower respiratory disease, with a stronger association between allocation to the proactive group and quit rate among those with chronic lower respiratory disease (odds ratio, 3.45; 95% confidence interval, 1.59-7.47) than those without chronic lower respiratory disease (odds ratio, 1.34; 95% confidence interval, 0.95-1.88; P for interaction with chronic lower respiratory disease = 0.03). Smokers with chronic lower respiratory disease may be more likely to respond to a proactive outreach intervention for tobacco cessation treatment than those without chronic lower respiratory disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608426).

Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

PubMed

Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

2004-08-01

Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at acute treatment but showed a gradual rise reflecting the stress imposed on the animals. The rise in cortisol levels was visualized to potentiate the cardiovascular and metabolic changes. The effects on insulin and thyroxin were similar to those of testosterone level showing normal or stimulatory effect with acute treatment followed by decreased levels of hormones with chronic treatment.

[The clinical analysis of atrial fibrillation of 1 310 in patients in Urumqi of China].

PubMed

Guo, Xiaohua; Zhang, Yu; Xu, Guojun; Zhou, Xianhui; Li, Lei; Tang, Baopeng

2014-05-01

To investigate the clinical features and current therapy of atrial fibrillation (AF) of inpatients in Urumqi, China. The clinical data of inpatients diagnosed with AF from January, 2008 to December, 2012, in 12 hospitals in Urumqi were retrospectively analyzed. Totally 1 310 AF inpatients were enrolled in this study with the age of (64.8 ± 3.3) years old and a men to women ratio of 1.39. Most patients were in age groups of 61-70 years (26.5%) and 71-80 years (27.6%). More patients with paroxysmal AF were at cardiac function class I-II (75.2%), while more patients with persistent AF were at cardiac function class III-IV (31.0%) (both P values < 0.05). The most common co-morbidities of AF were hypertension (49.2%), coronary heart disease (38.5%), diabetes mellitus (20.1%). Compared with patients of chronic AF, the patients of paroxysmal AF had higher success rates in amiodarone conversation and sinus rhythm maintenance after ablation (44.8% vs 29.9%, 87.5% vs 68.9%, P values < 0.05). Among the 1 310 inpatients, 992 patients (75.7%) received antithrombotic therapy. There were statistically significant differences in CHA2DS2 score and incidence rate of cerebral infarction among patients receiving aspirin, warfarin or rivaroxaban/other anticoagulation drugs [2(1, 3) vs 3(2, 4) vs 3(2, 5) and 6.3% vs 23.8% vs 30.2%, both P values < 0.05]. Our results of AF inpatients' age, gender, related disease distribution, AF types, incidence of stoke, therapeutic and epidemiological features are in accordance with the domestic and abroad reports.

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

PubMed

Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

1981-01-01

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p < 0.05). The dogs were then stratified into high- and low-risk subgroups based on the arrhythmic events of the antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

Treatment of chronic plantar fasciopathy with extracorporeal shock waves (review)

PubMed Central

2013-01-01

There is an increasing interest by doctors and patients in extracorporeal shock wave therapy (ESWT) for chronic plantar fasciopathy (PF), particularly in second generation radial extracorporeal shock wave therapy (RSWT). The present review aims at serving this interest by providing a comprehensive overview on physical and medical definitions of shock waves and a detailed assessment of the quality and significance of the randomized clinical trials published on ESWT and RSWT as it is used to treat chronic PF. Both ESWT and RSWT are safe, effective, and technically easy treatments for chronic PF. The main advantages of RSWT over ESWT are the lack of need for any anesthesia during the treatment and the demonstrated long-term treatment success (demonstrated at both 6 and 12 months after the first treatment using RSWT, compared to follow-up intervals of no more than 12 weeks after the first treatment using ESWT). In recent years, a greater understanding of the clinical outcomes in ESWT and RSWT for chronic PF has arisen in relationship not only in the design of studies, but also in procedure, energy level, and shock wave propagation. Either procedure should be considered for patients 18 years of age or older with chronic PF prior to surgical intervention. PMID:24004715

A Comprehensive Examination of Changes in Psychological Flexibility Following Acceptance and Commitment Therapy for Chronic Pain.

PubMed

Scott, Whitney; Hann, Katie E J; McCracken, Lance M

Acceptance and commitment therapy (ACT) for chronic pain aims to improve patient functioning by fostering greater psychological flexibility. While promising, ACT treatment process research in the context of chronic pain so far has only focused on a few of the processes of psychological flexibility. Therefore, this study aimed to more comprehensively examine changes in processes of psychological flexibility following an ACT-based treatment for chronic pain, and to examine change in these processes in relation to improvements in patient functioning. Individuals with chronic pain attending an interdisciplinary ACT-based rehabilitation program completed measures of pain, functioning, depression, pain acceptance, cognitive fusion, decentering, and committed action at pre- and post-treatment and during a nine-month follow-up. Significant improvements were observed from pre- to post-treatment and pre-treatment to follow-up on each of the treatment outcome and process variables. Regression analyses indicated that change in psychological flexibility processes cumulatively explained 6-27 % of the variance in changes in functioning and depression over both assessment periods, even after controlling for changes in pain intensity. Further research is needed to maximize the effectiveness of ACT for chronic pain, and to determine whether larger improvements in the processes of psychological flexibility under study will produce better patient outcomes, as predicted by the psychological flexibility model.

Treatment and follow up of children with chronic hepatitis C in Albania

PubMed Central

2012-01-01

Background Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. Patients and methods This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. Results At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% Conclusion The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained PMID:22244498

Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

PubMed Central

Kissin, Igor

2013-01-01

Background For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present. PMID:23874119

Endoscopic lung volume reduction coil treatment in patients with chronic hypercapnic respiratory failure: an observational study.

PubMed

Simon, Marcel; Harbaum, Lars; Oqueka, Tim; Kluge, Stefan; Klose, Hans

2017-01-01

Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure. A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015. During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV 1 ) from 0.5 ± 0.1 l to 0.6 ± 0.2 l ( p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l ( p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO 2 ) from 53 ± 5 mmHg to 48 ± 4 mmHg ( p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event. LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO 2 .

Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

PubMed

Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

2016-11-01

Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

Chronic Myeloproliferative Neoplasms Treatment (PDQ®)—Health Professional Version

Cancer.gov

Chronic Myeloproliferative Neoplasms (MPN) treatment varies widely depending on the specific diagnosis. Treatment options may include observation, phlebotomy, steroids, chemotherapy, immunotherapy, and stem cell transplant. Get detailed information about MPNs in this summary for clinicians.

Chronic Lymphocytic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Chronic lymphocytic leukemia (CLL) treatment options can include observation, steroids, chemotherapy, targeted therapy, and/or stem cell transplant. Get detailed information about newly diagnosed and recurrent CLL and available treatment modalities in this summary for clinicians.

Transforming Pain Medicine: Adapting to Science and Society

PubMed Central

Borsook, David; Kalso, Eija

2013-01-01

The field of chronic pain medicine is currently facing enormous challenges. The incidence of chronic pain is increasing worldwide, particularly in the developed world. As a result, chronic pain is imposing a growing burden on Western societies in terms of cost of medical care and lost productivity. This burden is exacerbated by the fact that despite research efforts and a huge expenditure on treatment for chronic pain, clinicians have no highly effective treatments or definitive diagnostic measures for patients. The lack of an objective measure for pain impedes basic research into the biological and psychological mechanisms of chronic pain and clinical research into treatment efficacy. The development of objective measurements of pain and ability to predict treatment responses in the individual patient is critical to improving pain management. Finally, pain medicine must embrace the development of a new evidence-based therapeutic model that recognizes the highly individual nature of responsiveness to pain treatments, integrates bio-psycho-behavioral approaches, and requires proof of clinical effectiveness for the various treatments we offer our patients. In the long-term these approaches will contribute to providing better diagnoses and more effective treatments to lessen the current challenges in pain medicine. PMID:23468059

Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

PubMed Central

Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

2016-01-01

A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

Curcumin, inflammation, and chronic diseases: how are they linked?

PubMed

He, Yan; Yue, Yuan; Zheng, Xi; Zhang, Kun; Chen, Shaohua; Du, Zhiyun

2015-05-20

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

PubMed

De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

2017-04-01

'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

Multidisciplinary pain facility treatment outcome for pain-associated fatigue.

PubMed

Fishbain, David A; Lewis, John; Cole, Brandly; Cutler, Brian; Smets, Eve; Rosomoff, Hubert; Rosomoff, Rennee Steele

2005-01-01

Fatigue is frequently found in chronic pain patients (CPPs) and may be etiologically related to the presence of pain. Fishbain et al. have recently demonstrated that chronic low back pain (LBP) and chronic neck pain patients are more fatigued than controls. The purpose of this study was to determine whether chronic LBP- and chronic neck pain-associated fatigue responded to multidisciplinary multimodal treatment not specifically targeted to the treatment of fatigue. A total of 85 chronic LBP and 33 chronic neck pain patients completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale (NPS), and Beck Depression Inventory on admission. In addition, an information tool was completed on each CPP by the senior author. This tool listed demographic information, primary and secondary pain diagnoses, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) psychiatric diagnoses assigned, pain location, pain precipitating event, type of injury, years in pain, number of surgeries, type of surgery, type of pain pattern, opioids consumed per day in morphine equivalents, worker compensation status, and whether, according to the clinical examination, the CPP had a neuropathic pain component. At completion of the multidisciplinary multimodal treatment, each CPP again completed the MFI. Student's t-test was utilized to test for statistical changes on the MFI five scales from pre- to post-treatment. Pearson and point-biserial correlations were utilized to determine which variables significantly correlated with MFI change scores. Variables found significant at less than or equal to 0.01 were utilized in a stepwise aggression analysis to find variables predictive of change in MFI scores. Multidisciplinary pain facility. Chronic LBP and chronic neck pain patients. Multidisciplinary multimodal treatment significantly improved CPP fatigue as measured by the MFI. The available variables utilized to predict fatigue best explained only a small percentage (28.9%) of the variance. Improvement in fatigue was related to NPS-10 scale scores (neuropathic pain) and a previous diagnosis of fibromyalgia. Multidisciplinary multimodal pain facility treatment improves chronic LBP- and neck pain-associated fatigue. At the present time we cannot predict this improvement with significant accuracy.

[The use of eurespal for the treatment of chronic laryngitis].

PubMed

Riabova, M A

2011-01-01

The author provides a rationale for the use of eurespal for the treatment of chronic laryngitis based on the pathogenetic concept of pathological condition. The results of a clinical study designed to evaluate the efficiency and safety of eurespal therapy in patients with chronic laryngitis are presented.

Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain

PubMed Central

Berta, Temugin; Qadri, Yawar; Tan, Ping-Heng; Ji, Ru-Rong

2018-01-01

Introduction Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states. PMID:28480765

Physical Therapy for Chronic Low Back Pain in North Carolina: Overuse, Underuse, or Misuse?

PubMed Central

Carey, Timothy S.; Holmes, George M.

2011-01-01

Background There are limited population-based studies of determinants of physical therapy use for chronic low back pain (LBP) and of the types of treatments received by individuals who see a physical therapist. Objective The purposes of this study were: (1) to identify determinants of physical therapy use for chronic LBP, (2) to describe physical therapy treatments for chronic LBP, and (3) to compare use of treatments with current best evidence on care for this condition. Design This study was a cross-sectional, population-based telephone survey of North Carolinians. Methods Five hundred eighty-eight individuals with chronic LBP who had sought care in the previous year were surveyed on their health and health care use. Bivariate and multivariable analyses were conducted to identify predisposing, enabling, and need characteristics associated with physical therapy use. Descriptive analyses were conducted to determine the use of physical treatments for individuals who saw a physical therapist. Use of treatments was compared with evidence from systematic reviews. Results Of our sample, 29.7% had seen a physical therapist in the previous year, with a mean of 15.6 visits. In multivariable analyses, receiving workers' compensation, seeing physician specialists, and higher Medical Outcomes Study 12-Item Short-Form Health Survey questionnaire (SF-12) physical component scores were positively associated with physical therapy use. Having no health insurance was negatively associated with physical therapy use. Exercise was the most frequent treatment received (75% of sample), and traction was the least frequent treatment received (7%). Some effective treatments were underutilized, whereas some ineffective treatments were overutilized. Limitations Only one state was examined, and findings were based on patient report. Conclusions Fewer than one third of individuals with chronic LBP saw a physical therapist. Health-related and non–health-related factors were associated with physical therapy use. Individuals who saw a physical therapist did not always receive evidence-based treatments. There are potential opportunities for improving access to and quality of physical therapy for chronic LBP. PMID:21330449

Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC).

PubMed

Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

2009-05-01

This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

Chronic Neck Pain: Making the Connection Between Capsular Ligament Laxity and Cervical Instability

PubMed Central

Steilen, Danielle; Hauser, Ross; Woldin, Barbara; Sawyer, Sarah

2014-01-01

The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain. The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome. When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability. Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability. PMID:25328557

Chronic neck pain: making the connection between capsular ligament laxity and cervical instability.

PubMed

Steilen, Danielle; Hauser, Ross; Woldin, Barbara; Sawyer, Sarah

2014-01-01

The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain. The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome. When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability. Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability.

Predicting balance improvements following STARS treatments in chronic ankle instability participants.

PubMed

Wikstrom, Erik A; McKeon, Patrick O

2017-04-01

Sensory Targeted Ankle Rehabilitation Strategies that stimulate sensory receptors improve postural control in chronic ankle instability participants. However, not all participants have equal responses. Therefore, identifying predictors of treatment success is needed to improve clinician efficiency when treating chronic ankle instability. Therefore, the purpose was to identify predictors of successfully improving postural control in chronic ankle instability participants. Secondary data analysis. Fifty-nine participants with self-reported chronic ankle instability participated. The condition was defined as a history of at least two episodes of "giving way" within the past 6 months; and limitations in self-reported function as measured by the Foot and Ankle Ability Measure. Participants were randomized into three treatment groups (plantar massage, ankle joint mobilization, calf stretching) that received 6, 5-min treatment sessions over a 2-week period. The main outcome measure was treatment success, defined as a participant exceeding the minimal detectable change score for a clinician-oriented single limb balance test. Participants with ≥3 balance test errors had a 73% probability of treatment success following ankle joint mobilizations. Participants with a self-reported function between limb difference <16.07% and who made >2.5 errors had a 99% probability of treatment success following plantar massage. Those who sustained ≥11 ankle sprains had a 94% treatment success probability following calf stretching. Self-reported functional deficits, worse single limb balance, and number of previous ankle sprains are important characteristics when determining if chronic ankle instability participants will have an increased probability of treatment success. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor alpha1.

PubMed

Pantos, Constantinos; Mourouzis, Iordanis; Malliopoulou, Vassiliki; Paizis, Ioannis; Tzeis, Stylianos; Moraitis, Panagiotis; Sfakianoudis, Konstantinos; Varonos, Dennis D; Cokkinos, Dennis V

2005-01-01

Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses.

Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

NASA Astrophysics Data System (ADS)

Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

2004-03-01

Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

[Application of cryogenic stimulation in treatment of chronic wounds].

PubMed

Vinnik, Iu S; Karapetian, G E; Iakimov, S V; Sychev, A G

2008-01-01

The authors have studied alterations occurring both in the ultrastructure of the cell matrix and in the microcirculatory bed of the chronic wound after local exposure to cryoagent. The up-to-date effective methods including laser Doppler flowmetry were used followed by correct statistical processing of the data obtained. The cryogenic stimulation of the wound was shown to result in considerably improved perfusion of the microcirculatory bed, epithelization and remodeling of the scar. It allowed transformation of a chronic process into acute and thus led to considerably accelerated process of regeneration. The developed method of cryogenic treatment of the chronic wound was used in 35 patients, allowed quicker healing of the chronic wounds and made ambulatory treatment of the patients 3 weeks shorter.

[The use of the antidepressant citalopran for the treatment of chronic pharyngitis and pharyngeal neurosis].

PubMed

Milinevskiĭ, I V; Shabaldina, E V; Shamova, I P; Shabaldin, A V

2011-01-01

The analysis of the efficacy of citalopran for the treatment of chronic pharyngitis and pharyngeal neurosis was carried out. The positive outcome of the treatment was documented in 95% of the patients.

Chronic constipation: an evidence-based review.

PubMed

Leung, Lawrence; Riutta, Taylor; Kotecha, Jyoti; Rosser, Walter

2011-01-01

Chronic constipation is a common condition seen in family practice among the elderly and women. There is no consensus regarding its exact definition, and it may be interpreted differently by physicians and patients. Physicians prescribe various treatments, and patients often adopt different over-the-counter remedies. Chronic constipation is either caused by slow colonic transit or pelvic floor dysfunction, and treatment differs accordingly. To update our knowledge of chronic constipation and its etiology and best-evidence treatment, information was synthesized from articles published in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Levels of evidence and recommendations were made according to the Strength of Recommendation taxonomy. The standard advice of increasing dietary fibers, fluids, and exercise for relieving chronic constipation will only benefit patients with true deficiency. Biofeedback works best for constipation caused by pelvic floor dysfunction. Pharmacological agents increase bulk or water content in the bowel lumen or aim to stimulate bowel movements. Novel classes of compounds have emerged for treating chronic constipation, with promising clinical trial data. Finally, the link between senna abuse and colon cancer remains unsupported. Chronic constipation should be managed according to its etiology and guided by the best evidence-based treatment.

Management of familial benign chronic pemphigus

PubMed Central

Arora, Harleen; Bray, Fleta N; Cervantes, Jessica; Falto Aizpurua, Leyre A

2016-01-01

Benign familial chronic pemphigus or Hailey–Hailey disease is caused by an autosomal dominant mutation in the ATP2C1 gene leading to suprabasilar acantholysis. The disease most commonly affects intertriginous areas symmetrically. The chronic nature of the disease and multiple recurrences make the disease bothersome for patients and a treatment challenge for physicians. Treatments include topical and/or systemic agents and surgery including laser. This review summarizes the available treatment options. PMID:27695354

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-10-1-0962 TITLE: Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury...164. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0962 Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced...month follow-up period post-hyperbaric oxygen treatment. 1 additional subject is scheduled to be screened in October 2016 and 3 are awaiting first

Depression treatment decreases healthcare expenditures among working age patients with comorbid conditions and type 2 diabetes mellitus along with newly-diagnosed depression.

PubMed

Bhattacharya, Rituparna; Shen, Chan; Wachholtz, Amy B; Dwibedi, Nilanjana; Sambamoorthi, Usha

2016-07-19

There are many studies in the literature on the association between depression treatment and health expenditures. However, there is a knowledge gap in examining this relationship taking into account coexisting chronic conditions among patients with diabetes. We aim to analyze the association between depression treatment and healthcare expenditures among adults with Type 2 Diabetes Mellitus (T2DM) and newly-diagnosed depression, with consideration of coexisting chronic physical conditions. We used multi-state Medicaid data (2000-2008) and adopted a retrospective longitudinal cohort design. Medical conditions were identified using diagnosis codes (ICD-9-CM and CPT systems). Healthcare expenditures were aggregated for each month for 12 months. Types of coexisting chronic physical conditions were hierarchically grouped into: dominant, concordant, discordant, and both concordant and discordant. Depression treatment categories were as follows: antidepressants or psychotherapy, both antidepressants and psychotherapy, and no treatment. We used linear mixed-effects models on log-transformed expenditures (total and T2DM-related) to examine the relationship between depression treatment and health expenditures. The analyses were conducted on the overall study population and also on subgroups that had coexisting chronic physical conditions. Total healthcare expenditures were reduced by treatment with antidepressants (16 % reduction), psychotherapy (22 %), and both therapy types in combination (28 %) compared to no depression treatment. Treatment with both antidepressants and psychotherapy was associated with reductions in total healthcare expenditures among all groups that had a coexisting chronic physical condition. Among adults with T2DM and chronic conditions, treatment with both antidepressants and psychotherapy may result in economic benefits.

Efficacy and safety of extracorporeal shock wave lithotripsy for chronic pancreatitis.

PubMed

Vaysse, Thibaut; Boytchev, Isabelle; Antoni, Guillemette; Croix, Damien Sainte; Choury, André Daniel; Laurent, Valérie; Pelletier, Gilles; Buffet, Catherine; Bou-Farah, Rita; Carbonnel, Franck

2016-11-01

There is still uncertainty regarding the efficacy and optimal modalities of extracorporeal shock wave lithotripsy (ESWL) in the treatment of chronic pancreatitis. The aims of the present study were to assess the safety and the efficacy of ESWL, either alone or followed by therapeutic endoscopic retrograde cholangiopancreatography (adjuvant ERCP) and to determine predictive factors of efficacy, in a real-life setting. This study included all consecutive patients who underwent an ESWL in a single University Hospital between 2001 and 2012. The indication for ESWL was obstructive stone(s) of the main pancreatic duct resulting in either painful chronic pancreatitis or recurrent acute pancreatitis. Success was defined by resolution of pain, no analgesic treatment, no acute pancreatitis and no surgical treatment for chronic pancreatitis 6 months after the ESWL. One hundred and forty-six patients were studied; 6/146 (4%) had a complication of ESWL. Among the 132 patients in whom follow-up was completed, 91 (69%) had an adjuvant ERCP. After 6 months of follow-up, 100/132 (76%) patients achieved success. In multivariate analysis, the single significant predictive factor of the success of the ESWL treatment was chronic pain (p = 0.03). Patients who had chronic pain and needed opioid treatment had less chance of success than patients without chronic pain (OR 95%CI 0.31 [0.07-1.14]). We found no difference in the success rates between patients who underwent adjuvant ERCP and those who had ESWL only (p = 0.93). This study shows that the ESWL is a safe and effective treatment for patients with chronic pancreatitis and obstructive stones within the main pancreatic duct. Systematic association with therapeutic ERCP appears to provide no additional benefit and is therefore not recommended.

Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

PubMed

Ibrahim, Uroosa; Saqib, Amina; Dhar, Vidhya; Odaimi, Marcel

2018-01-01

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

Chronic Pain

MedlinePlus

... of mainstream medical care. Acupuncture and massage are examples of these treatments. Talk to your doctor before trying any CAM procedures. Severe cases of chronic pain could require more invasive treatment. ...

Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease

PubMed Central

Storer, Barry E.; Lee, Stephanie J.; Carpenter, Paul A.; Sandmaier, Brenda M.; Flowers, Mary E. D.; Martin, Paul J.

2013-01-01

This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD. PMID:23321253

Proposal of a model for multidisciplinary treatment program of chronic migraine with medication overuse: preliminary study.

PubMed

Grazzi, L; Prunesti, A; Bussone, G

2015-05-01

The treatment of patients with chronic migraine associated with medication overuse is challenging in clinical practice; different strategies of treatment have been recently developed, multidisciplinary treatment approaches have been developed in academic headache centers. Education and support of patients are necessary to improve patients' adherence to pharmacological treatments as well as to non-pharmacological therapies. This study reports a clinical experience conducted at our Headache center with a group of female patients, suffering from chronic migraine complicated by medication overuse, treated by a multidisciplinary approach and followed for a period of 1 year after withdrawal. Results confirm the efficacy of a multifaceted treatment to manage this problematic category of patients.

A Unified, Transdiagnostic Treatment for Adolescents with Chronic Pain and Comorbid Anxiety and Depression

ERIC Educational Resources Information Center

Allen, Laura B.; Tsao, Jennie C. I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

2012-01-01

Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional…

Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

ERIC Educational Resources Information Center

Braam, W.; Didden, R.; Smits, M.; Curfs, L.

2008-01-01

Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

Chronic pancreatitis.

PubMed

DiMagno, Matthew J; DiMagno, Eugene P

2012-09-01

We review important new clinical observations in chronic pancreatitis reported in 2011. Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct ± pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis.

Chronic pancreatitis.

PubMed

Gupte, Anand R; Forsmark, Chris E

2014-09-01

We review selected important clinical observations in chronic pancreatitis reported in 2013. Early diagnosis of chronic pancreatitis remains difficult, although newer techniques utilizing endoscopic ultrasonography-elastography and MRI hold promise. Patients with chronic pancreatitis are at risk of nutritional deficiencies. Osteoporosis, osteopenia, and bone fracture are particularly common in these patients, and require active intervention and treatment. Diabetes caused by chronic pancreatitis, type 3c diabetes, has specific characteristics and requires careful management. Antioxidants and neuromodulators may decrease pain in some patients with chronic pancreatitis. Endoscopic treatment is effective and can be utilized in patients with painful chronic pancreatitis, although randomized trials demonstrate that surgical therapy is somewhat more durable and effective. Although surgery has typically been a last resort, some advocate early surgical intervention but the optimal time remains unknown. Early diagnosis of pancreatitis may be improved by newer techniques associated with endoscopic ultrasonography imaging. Treatment of nutritional deficiencies and diabetes is an important aspect of treating chronic pancreatitis. Pain relief with adjunct means of pain modulation should be tried before starting narcotics for pain control. Endoscopic therapy is appropriate for treating chronic pancreatitis and its local complications and surgical intervention can be considered early in carefully selected individuals.

Stochastic modelling to assess economic effects of treatment of chronic subclinical mastitis caused by Streptococcus uberis.

PubMed

Steeneveld, Wilma; Swinkels, Jantijn; Hogeveen, Henk

2007-11-01

Chronic subclinical mastitis is usually not treated during the lactation. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model included the probability of cure after treatment, probability of the cow becoming clinically diseased, transmission of infection to other cows, and physiological effects of the infection. Using basic input parameters for Dutch circumstances, the average economic costs per cow of an untreated chronic subclinical mastitis case caused by Str. uberis in a single quarter from day of diagnosis onwards was euro109. With treatment, the average costs were higher (euro120). Thus, for the average cow, treatment was not efficient economically. However, the risk of high costs was much higher when cows with chronic subclinical mastitis were not treated. A sensitivity analysis showed that profitability of treatment of chronic subclinical Str. uberis mastitis depended on farm-specific factors (such as economic value of discarded milk) and cow-specific factors (such as day of diagnosis, duration of infection, amount of transmission to other cows and cure rate). Therefore, herd level protocols are not sufficient and decision support should be cow specific. Given the importance of cow-specific factors, information from the current model could be applied to automatic decision support systems.

The Effect of Photodynamic Therapy in the Treatment of Chronic Periodontitis: A Review of Literature.

PubMed

Meimandi, Mansour; Talebi Ardakani, Mohammad Reza; Esmaeil Nejad, Azadeh; Yousefnejad, Parisa; Saebi, Khosro; Tayeed, Mohammad Hossein

2017-01-01

Introduction: Chronic periodontitis is the most common periodontal disease which is related to the chronic accumulation of bacterial plaque. Since mechanical methods are not sufficient in the treatment of this disease, administration of local/systemic antibiotic is recommended following mechanical debridement. However, side effects of antibiotics such as microbial resistance and patient allergy led to development of alternative methods. One of these suggested methods is the antimicrobial photodynamic therapy (aPDT). PDT is a local noninvasive treatment modality without the side effects caused by antibiotics. The aim of this study was to review the articles related to the application of PDT with laser in the treatment of chronic periodontitis. Review of literature: In the present review of literature, the authors used key words such as chronic periodontitis, laser and photodynamic therapy, and conducted a literature search via Google Scholar and PubMed for the period of 1990 to 2015. A total of 47 articles in English were found. The articles that were not associated with the topic of research and review articles were deleted and only clinical trials were evaluated. After reviewing 23 articles' abstracts, the full texts of 16 articles were analyzed. Conclusion: Considering the safety, the lack of side effects and general advantages like more patient compliance, the PDT treatment with scaling and root planing (SRP) is recommended as an efficient adjunctive modality for the treatment of localized chronic periodontitis especially during the maintenance phase in non-surgical treatment.

A study of chronic fatigue in Norwegian cervical cancer survivors.

PubMed

Steen, Rita; Dahl, Alv A; Hess, Siri Lothe; Kiserud, Cecilie E

2017-09-01

Chronic fatigue after treatment is a common adverse event in cancer patients, but there are few studies in long-term survivors of cervical cancer. The aim of this investigation was to explore the prevalence of chronic fatigue and its association with various clinical and treatment-related factors in a population-based cohort of Norwegian cervical cancer survivors treated by any modality. All patients, treated for cervical cancer from 2000 through 2007 in the Health Region of South-Eastern Norway, cancer-free, alive and aged ≤75years by the end 2013 (n=822) received a questionnaire covering chronic fatigue and other clinical variables. 461 of 822 survivors (56%) completed the questionnaire and 382 entered the analyses. Chronic fatigue was reported by 23% (95% confidence interval 19%-27%) with a median age of 52years (range 32-75) at survey, 11years (range 7-15) after diagnosis. Among survivors treated by minimal invasive- or radical surgery, 19% had chronic fatigue, while the prevalence was 28% in those treated with radiation and concomitant chemotherapy (chemoradiation). The chronic fatigue group reported significantly more cardiovascular disease, obesity, less physical activity, more treatment-related symptom experience, more menopausal symptoms, higher levels of anxiety and depressive symptoms, and poorer quality of life than the non-fatigued group. In multivariate analysis only increased level of depression and poorer global quality of life were significantly associated with chronic fatigue. Chronic fatigue was reported by 23% of long-term survivors after cervical cancer at a mean of 11years after treatment. Some of the associated factors are amenable to prevention and/or treatment and should be subjects of attention at follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Operant Behavioral and Cognitive-Behavioral Group Treatment for Chronic Low Back Pain.

ERIC Educational Resources Information Center

Turner, Judith A.; Clancy, Steve

1988-01-01

Assigned chronic low back pain patients to operant behavioral (OB) treatment, cognitive-behavioral (CB) treatment, or waiting-list (WL) condition. Both treatments resulted in decreased physical and psychosocial disability. OB patients' greater improvement leveled off at followup; CB patients continued to improve over the 12 months following…

Absence from school related to cancer and other chronic conditions.

PubMed Central

Charlton, A; Larcombe, I J; Meller, S T; Morris Jones, P H; Mott, M G; Potton, M W; Tranmer, M D; Walker, J J

1991-01-01

Absence from school during the first year after starting major treatment for cancer or chronic or orthopaedic conditions was examined. Retrospective data were collected on 72 children and obtained from hospital records, school registers, and interviews with parents and teachers. Median initial absences caused by treatment were 91, 29-5, and 15 days for cancer, chronic, and orthopaedic patients respectively. The mean proportions of the remaining school time in the year occupied by absences caused by treatment and those not caused by treatment were respectively 17% and 17% for oncology patients, 8% and 12% for chronic patients, and 2% and 11% for orthopaedic patients. The only significant factor associated with the amount of absence caused by treatment was the type of illness. Increased absence not caused by treatment was associated with the amount of treatment time and the patient being a girl. The proportion of absence not caused by treatment decreased if the mother was educated beyond the age of 18. The possible reasons for and effects of excess absence are discussed. PMID:1953006

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed

Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

2016-03-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Neuromodulatory treatments for chronic pain: efficacy and mechanisms

PubMed Central

Jensen, Mark P.; Day, Melissa A.; Miró, Jordi

2017-01-01

Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable ‘first-line’ approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain. PMID:24535464

Diagnosis and treatment of chronic constipation – a European perspective

PubMed Central

Tack, J; Müller-Lissner, S; Stanghellini, V; Boeckxstaens, G; Kamm, M A; Simren, M; Galmiche, J-P; Fried, M

2011-01-01

Background Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. Purpose We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted. PMID:21605282

Neuromodulatory treatments for chronic pain: efficacy and mechanisms.

PubMed

Jensen, Mark P; Day, Melissa A; Miró, Jordi

2014-03-01

Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable 'first-line' approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain.

Attitudes toward mental illness in adults by mental illness-related factors and chronic disease status: 2007 and 2009 Behavioral Risk Factor Surveillance System.

PubMed

Kobau, Rosemarie; Zack, Matthew M

2013-11-01

We examined how attitudes toward mental illness treatment and its course differ by serious psychological distress, mental illness treatment, chronic disease, and sociodemographic factors using representative state-based data. Using data from jurisdictions supporting the Behavioral Risk Factor Surveillance System's Mental Illness and Stigma Module (35 states, the District of Columbia, and Puerto Rico), we compared adjusted proportions of adults agreeing that "Treatment can help people with mental illness lead normal lives" (treatment effectiveness) and that "People are generally caring and sympathetic to people with mental illness" (supportive environment), by demographic characteristics, serious psychological distress, chronic disease status, and mental illness treatment. Attitudes regarding treatment effectiveness and a supportive environment for people with mental illness varied within and between groups. Most adults receiving mental illness treatment agreed that treatment is effective. Fewer adults with serious psychological distress than those without such distress agreed that treatment is effective. Fewer of those receiving treatment, those with psychological distress, and those with chronic disease perceived the environment as supportive. These data can be used to target interventions for population subgroups with less favorable attitudes and for surveillance.

[Recognition and thoughts for diagnosis and treatment of chronic prostatitis in integrated traditional Chinese and Western medicine].

PubMed

Song, Shu-qi; Zhang, Ya-qiang

2009-12-01

The etiology, pathogenesis, and diagnostic criteria of chronic prostatitis were reviewed in this article. Based on clinical practice, the authors systematically discussed the thoughts and methods for the treatment of chronic prostatitis by integrated traditional Chinese and Western medicine. Meanwhile, advice on disputed problems in clinical study of prostatits were given, such as curative effect estimation value of the number of leukocytes in expressed prostatic secretion (EPS) and bacterial culture in EPS, the opportunity and treatment course of antibiotics, National Institutes of Health chronic prostatitis symptom index, classification of syndromes of traditional Chinese medicine (TCM), TCM symptom score, and clinical study period.

Clinical management of chronic TMD pain.

PubMed

Miller, D B

1998-01-01

Chronic Pain extracts a "penalty" on society now estimated to be well in excess of $100 million per year. The "penalty" that Chronic Pain extracts from its victims is incalculable. Chronic Pain is a major component of Temporomandibular Disorders. The current neurological theory of the mechanism of chronic TMD pain is explored along with the current modes of treatment. Pharmacological management of Chronic Pain in a clinical setting is outlined. Dentists are involved in pain management on a daily basis. Dentists treat pain both prophylacticly and in response to specific patient symptoms. Most dental treatment involves some type of pain management. We, dentists, have become very adept at managing acute pain. We have much greater difficulty managing chronic pain. The word "pain" derives from the Greek word for penalty, and appeared to them to be a "penalty" inflicted by the gods. In 1984, Bonica estimated that one-third of all Americans suffered from some kind of chronic pain at a "penalty" to society of $65 Billion annually in medical expenses and lost wages and productivity. This figure is certainly much greater now. Chronic pain can be a very complex problem that can require a multidisciplinary approach to treatment. Chronic pain in the dental setting is most frequetly caused by prolonged Temporomandibular Disorders.

Surgical Management of Chronic Pancreatitis.

PubMed

Parekh, Dilip; Natarajan, Sathima

2015-10-01

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav1.2 over-expressing cells.

PubMed

Lagrutta, Armando; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

2016-10-01

Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca(2+) transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca(2+) channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca(2+) stores, and SEA-0400, a Na(+)/Ca(2+) exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav1.2 ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav1.2 channel inhibition by AMIO, but did not affect inhibition of Cav1.2 by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca(2+)-handling mechanisms. Additional study in a Cav1.2 HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca(2+) channels. Copyright © 2016 Elsevier Inc. All rights reserved.

Worsening heart failure in the setting of dronedarone initiation.

PubMed

Coons, James C; Plauger, Kara M; Seybert, Amy L; Sokos, George G

2010-09-01

To describe a challenging patient case in which dronedarone was selected for a patient with atrial fibrillation and heart failure; the drug may have been associated with worsening heart failure, leading to acute renal and hepatic failure. A 47-year-old male with a history of heart failure with New York Heart Association class III-IV symptoms presented to our institution with ventricular fibrillation and ventricular tachycardia storm. Torsade de pointes secondary to a combination of dofetilide and hypokalemia was determined to be the etiology. Upon stabilization, the patient was initiated on dronedarone 400 mg orally twice daily by the electrophysiology service for atrial fibrillation. The patient had a questionable history of amiodarone intolerance. By hospital day 9 (day 4 of dronedarone therapy), the patient demonstrated a clinical picture consistent with acute renal and hepatic failure possibly due to worsening heart failure. Dronedarone was discontinued on hospital day 10. He was subsequently transferred to an outside hospital where he required milrinone therapy for cardiogenic shock. Laboratory markers of renal and hepatic function improved over the remainder of his hospitalization and he was discharged on hospital day 20. Dronedarone is a newly approved antiarrhythmic agent with multichannel blocking properties similar to amiodarone. Use of the Naranjo probability scale determined that this patient's worsening heart failure leading to acute renal and hepatic failure was possibly caused by dronedarone. The implication from the ANDROMEDA trial as well as our experience in this case is that dronedarone should be used cautiously in patients with heart failure and avoided in patients specifically outlined in the product labeling. This case report, to our knowledge, represents the first published postmarketing report of worsening heart failure complicated by multiorgan dysfunction in the setting of dronedarone initiation. Dronedarone use must be approached with caution in patients with a history of heart failure.

Best candidates for cognitive treatment of illness perceptions in chronic low back pain: results of a theory-driven predictor study.

PubMed

Siemonsma, Petra C; Stuvie, Ilse; Roorda, Leo D; Vollebregt, Joke A; Lankhorst, Gustaaf J; Lettinga, Ant T

2011-04-01

The aim of this study was to identify treatment-specific predictors of the effectiveness of a method of evidence-based treatment: cognitive treatment of illness perceptions. This study focuses on what treatment works for whom, whereas most prognostic studies focusing on chronic non-specific low back pain rehabilitation aim to reduce the heterogeneity of the population of patients who are suitable for rehabilitation treatment in general. Three treatment-specific predictors were studied in patients with chronic non-specific low back pain receiving cognitive treatment of illness perceptions: a rational approach to problem-solving, discussion skills and verbal skills. Hierarchical linear regression analysis was used to assess their predictive value. Short-term changes in physical activity, measured with the Patient-Specific Functioning List, were the outcome measure for cognitive treatment of illness perceptions effect. A total of 156 patients with chronic non-specific low back pain participated in the study. Rational problem-solving was found to be a significant predictor for the change in physical activity. Discussion skills and verbal skills were non-significant. Rational problem-solving explained 3.9% of the total variance. The rational problem-solving scale results are encouraging, because chronic non-specific low back pain problems are complex by nature and can be influenced by a variety of factors. A minimum score of 44 points on the rational problem-solving scale may assist clinicians in selecting the most appropriate candidates for cognitive treatment of illness perceptions.

[New guidelines on chronic pancreatitis : interdisciplinary treatment strategies].

PubMed

Lerch, M M; Bachmann, K A; Izbicki, J R

2013-02-01

Chronic pancreatitis is a common disorder associated with significant morbidity and mortality. Interdisciplinary consensus guidelines have recently updated the definitions and diagnostic criteria for chronic pancreatitis and provide a critical assessment of therapeutic procedures. Diagnostic imaging relies on endoscopic ultrasound (EUS) as the most sensitive technique, whereas computed tomography (CT) and magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) remain a frequent preoperative requirement. Endoscopic retrograde cholangiopancreatography (ERCP) is now used mostly as a therapeutic procedure except for the differential diagnosis of autoimmune pancreatitis. Complications of chronic pancreatitis, such as pseudocysts, duct stricture and intractable pain can be treated with endoscopic interventions as well as open surgery. In the treatment of pseudocysts endoscopic drainage procedures now prevail while pain treatment has greater long-term effectiveness following surgical procedures. Currently, endocopic as well as surgical treatment of chronic pancreatitis require an ever increasing degree of technical and medical expertise and are provided increasingly more often by interdisciplinary centres. Surgical treatment is superior to interventional therapy regarding the outcome of pain control and duodenum-preserving pancreatic head resection is presently the surgical procedure of choice.

A Unified, Transdiagnostic Treatment for Adolescents With Chronic Pain and Comorbid Anxiety and Depression

PubMed Central

Allen, Laura B.; Tsao, Jennie C.I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

2017-01-01

Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional disorders and suggest the possibility of extending these interventions to chronic pain and pain-related dysfunction. This case report describes the use of a unified protocol for treatment of an adolescent boy with chronic daily headache and social anxiety and an adolescent girl with whole body pain and depression. Following weekly, 50-minute individual treatment sessions, the boy demonstrated notable improvement in emotional symptoms, emotion regulation skills, somatization, and functional disability. The girl showed some improvement on measures of anxiety and depression, although there appeared to be a worsening of pain symptoms and somatization. However, both patients demonstrated improvement over follow-up. This case study illustrates the potential utility of a unified treatment approach targeting pain and emotional symptoms from an emotion regulation perspective in an adolescent population. PMID:28824271

[Variants of choice of surgical treatment of chronic pancreatitis in consideration of morphological changes in the pancreas].

PubMed

Priadko, A S; Maĭstrenko, N A; Romashchenko, P N

2014-01-01

The results of examination and treatment of 445 patients with chronic pancreatitis were analyzed. It was established, that 298 (67%) patients had indications for treatment in the conditions of surgical hospital. The patients were divided into three groups according to the modified pancreatitis classification of Marseilles-Rome 1988. There were the calcifying form (n = 78), obstructive form (n = 81), inflammatory form (n = 139). The application of modern methods of diagnostics and treatment of chronic pancreatitis allowed modifying the classification by selection of subgroups for each form of the disease. It was stated, that the substantiation of variants of surgical treatment of chronic pancreatitis in consideration of morphological changes in the pancreas could improve the possibilities of medical care plan for patients with minimal complications and good quality of life in long-term period of time.

The representation of getting ill in adolescents with systemic lupus erythematosus.

PubMed

Ceppas Resende, Ondina Lúcia; Barbosa, Maria Tereza Serrano; Simões, Bruno Francisco Teixeira; Velasque, Luciane de Souza

This study, developed in a federal hospital in the city of Rio de Janeiro, has aimed to analyze the social representation of chronic disease and its treatment, in the perspective of adolescents and their caregivers. The sample consisted of 31 adolescents (11-21 years) with systemic lupus erythematosus and 19 caregivers (32-66 years), followed in the pediatrics and in the internal medicine outpatient clinics for a period of six months. Data was collected from the free association of words test, using chronic disease and treatment of chronic disease impulses, and later submitted to the Multiple Correspondence Analysis using the R software. The group of adolescents associated the impulse chronic disease with the words medication, bad, illness, difficulty, no cure, faith and joy; and in the group of caregivers, to care, treatment, no cure and the word 'no'. The impulse treatment of chronic disease was associated, in the group of adolescents, with the words patience, improvement, help, affection, care and bad; and in the group of caregivers, to caring, hope, schedule, knowledge, obedience, medication, professional and improvement. Caregivers also associated impulses and words according to age: chronic disease was associated with the word care (over 61 years), pain and impotence (42-61 years), treatment (22-41 years); and treatment of chronic disease, with the words strength (over 61 years), professional, knowledge and improvement (42-61 years), affection and schedule (22-41 years). Considering as subjective and dynamic the experience of getting ill, knowing the representations can contribute to the orientation of conduct and type of psychotherapeutic intervention needed. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats.

PubMed

Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri; Slade, Susan; Wells, Corinne; Rezvani, Amir H; Rose, Jed E

2016-08-01

Chronic nicotine infusion via transdermal patches has been widely shown to assist with smoking cessation. In particular, transdermal nicotine treatment prior to quitting smoking helps reduce ad libitum smoking and aids cessation Rose et al. (Nicotine Tob Res 11:1067-75, 2009). However, despite this success, the majority of smokers who use transdermal nicotine fail to permanently quit smoking. Additional treatments are needed. Tobacco addiction does not just depend on nicotinic receptor systems; a variety of neural systems are involved, including dopamine, norepinepherine, serotonin, and histamine. Given the involvement of a variety of neural systems in the circuits of addiction, combination therapy may offer improved efficacy for successful smoking cessation beyond single treatments alone. We have found that pyrilamine, an H1 histamine antagonist, significantly decreases nicotine self-administration in rats. The current study was conducted to confirm the effect of chronic nicotine infusion on ongoing nicotine self-administration and resumed access after enforced abstinence and to determine the interaction of chronic nicotine with an H1 antagonist treatment. Chronic nicotine infusion via osmotic minipump (2.5 and 5 mg/kg/day for 28 days) significantly reduced nicotine self-administration in a dose-dependent manner. Chronic nicotine infusion also reduced the resumption of nicotine self-administration after enforced abstinence. Chronic pyrilamine infusion (25 mg/kg/day for 14 days) also significantly reduced nicotine self-administration. The combination of chronic nicotine and pyrilamine reduced nicotine self-administration to a greater extent than treatment with either drug alone.

The economic costs of chronic pain among a cohort of treatment seeking adolescents in the United States

PubMed Central

Groenewald, Cornelius B.; Essner, Bonnie S.; Wright, Davene; Fesinmeyer, Megan D.; Palermo, Tonya M.

2014-01-01

The aim of this study was to assess the economic cost of chronic pain among adolescents receiving interdisciplinary pain treatment. Information was gathered from 149 adolescents (ages 10-17) presenting for evaluation and treatment at interdisciplinary pain clinics in the United States. Parents completed a validated measure of family economic attributes, the Client Service Receipt Inventory, to report on health service use and productivity losses due to their child's chronic pain retrospectively over 12 months. Health care costs were calculated by multiplying reported utilization estimates by unit visit costs from the 2010 Medical Expenditure Panel Survey. The estimated mean and median costs per participant were $11,787 and $6,770 respectively. Costs were concentrated in a small group of participants, the top 5 % of those patients incurring the highest costs accounted for 30 % of total costs while the lower 75 % of participants accounted for only 34 % of costs. Total costs to society for adolescents with moderate to severe chronic pain were extrapolated to $19.5 billion annually in the U.S. The cost of childhood chronic pain presents a substantial economic burden to families and society. Future research should focus on predictors of increased health services use and costs in adolescents with chronic pain. Perspective This cost of illness study comprehensively estimates the economic costs of chronic pain in a cohort of treatment-seeking adolescents. The primary driver of costs was direct medical costs followed by productivity losses. Because of its economic impact, policy makers should invest resources in the prevention, diagnosis, and treatment of chronic pediatric pain. PMID:24953887

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.

PubMed

Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

2005-12-07

To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. After one course of treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio of CD4(+)/CD8(+) increased as compared to those before the treatment but the level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze.

PubMed

Gomes, Karina Santos; de Carvalho-Netto, Eduardo Ferreira; Monte, Kátia Cristina Da Silva; Acco, Bruno; Nogueira, Paulo José de Campos; Nunes-de-Souza, Ricardo Luiz

2009-03-30

The elevated T-maze (ETM) is an animal model of anxiety-like behavior that assesses two different defensive behavioral tasks in the same animal-acquisition of inhibitory avoidance and latency to escape from an open and elevated arm. In rats, cute and chronic treatments with anxiolytic-like drugs impair avoidance acquisition while only chronic administration of panicolytic-like drugs impairs open arm withdrawal. To date, only the acute effects of anxiolytic/anxiogenic or panicolytic/panicogenic drugs have been tested in the mouse ETM and the results have partially corroborated those found in the rat ETM. This study investigated the effects of acute (a single intraperitoneal injection 30 min before testing) and chronic (daily i.p. injections for 15 consecutive days) treatment with imipramine or fluoxetine, non-selective and selective serotonin reuptake inhibitors, respectively, on inhibitory avoidance and escape tasks in the mouse ETM. Neither acute nor chronic treatment with imipramine (0, 1, 5 or 10 mg/kg, i.p.) significantly changed the behavioral profile of mice in the two ETM tasks. Interestingly, while acute fluoxetine (0, 5, 10, 20 or 40 mg/kg, i.p.) facilitated inhibitory avoidance and impaired escape latency, chronic treatment (0, 5, 20 or 40 mg/kg, i.p.) with this selective serotonin reuptake inhibitor (SSRI) produced an opposite effect, i.e., it impaired inhibitory avoidance acquisition and facilitated open arm withdrawal. Importantly, acute or chronic treatment with imipramine (except at the highest dose that increased locomotion when given acutely) or fluoxetine failed to alter general locomotor activity in mice as assessed in an ETM in which all arms were enclosed by lateral walls (eETM). These results suggest that inhibitory avoidance acquisition is a useful task for the evaluation of acute and chronic effects of SSRI treatment on anxiety in mice. However, as open arm latency was actually increased and reduced by acute and chronic fluoxetine, respectively, this does not seem to be a useful measure of escape from a proximal threat in this species.

The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior.

PubMed

Ferraz, Marcia M D; Quintella, Suelen L; Parcial, André L N; Ferraz, Marcos R

2016-01-01

Ferraz MMD, Quintella SL, Parcial ALN, Ferraz MR. The effects of sildenafil citrate and L-NAME on male rat sexual behaviour. PHARMACOL BIOCHEM BEHAV. Erectile dysfunction (ED) affects up to 50% of men between 40 and 70years of age. Significant advances in the pharmacological treatment of ED occurred in recent years, most notably the introduction of the first oral selective phosphodiesterase type-5 inhibitor, sildenafil. This study investigated the effectiveness of chronic oral treatment with L-NAME in rats as an experimental model of erectile dysfunction to evaluate new pharmacological agents that affect the sexual response. The effects of chronic oral L-NAME treatment, separately or in combination with sildenafil, on the sexual behaviour of male rats were evaluated. Filtered water was used as a control. Acute administration of L-NAME did not alter the sexual response compared with control, but sildenafil administration facilitated sexual behaviour after acute and chronic administration. Chronic L-NAME treatment inhibited motivational and consummatory measures of male rat sexual behaviour. Sildenafil prevented the inhibitory effects of L-NAME. The present results confirm that chronic oral treatment with a nitric oxide synthase inhibitor may be a relevant peripheral ED model to evaluate the effects of drugs on erectile function of male rats. Copyright © 2016 Elsevier Inc. All rights reserved.

[Manegement and countermeasures against tuberculous patients with chronic positive sputum].

PubMed

Sato, K

1996-01-01

We studied measures for the prevention and treatment of chronic positive-sputum tuberculosis. Most physicians treating chronic intractable pulmonary tuberculosis are concerned about treatment and control measures. However, both the medical and social aspects of the disease must be dealt with. The study of the medical aspects of tuberculosis used data on patients at the Tokyo National Chest Hospital and other sanitoria in Japan. The socioeconomic study employed data from a health center in Tokyo. Recently, new cases of tuberculosis are concentrated in socioeconomically high risk groups, such as the homeless and illegal aliens, in a few large cities. Patients in these groups often have multidrug-resistant tuberculosis (MDRTB), including many patients with relapsing tuberculosis. However, it is dificult to keep such patients under treatment because of poor compliance and patient dropout. The results of our study are summarized as follows: 1. Prevention and treatment of chronic intractable tuberculosis should involve both the medical and socioeconomic aspects of the disease. 2. Surgical treatment offers benefits for patients with chronically positive sputum. Therefore, surgery should be recommended to patients with chronic intractable MDRTB. 3. If resistance to both isoniazid and rifampin is demonstrated, it is better to replace all ineffective drugs with a new effective regimen than to add a single drug to a failing regimen.

Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis

PubMed Central

He, Shuijin; Bausch, Suzanne B.

2013-01-01

Chronic N-methyl-D-aspartate receptor (NMDAR) blockade with high affinity competitive and uncompetitive antagonists can lead to seizure exacerbation, presumably due to an imbalance in glutamatergic and GABAergic transmission. Acute administration of the moderate affinity NMDAR antagonist memantine in vivo has been associated with pro- and anticonvulsive properties. Chronic treatment with memantine can exacerbate seizures. Therefore, we hypothesized that chronic memantine treatment would increase glutamatergic and decrease GABAergic transmission, similar to high affinity competitive and uncompetitive antagonists. To test this hypothesis, organotypic hippocampal slice culture were treated for 17–21 days with memantine and then subjected to electrophysiological recordings. Whole-cell recordings from dentate granule cells revealed that chronic memantine treatment slightly, but significantly increased sEPSC frequency, mEPSC amplitude and mEPSC charge transfer, consistent with minimally increased glutamatergic transmission. Chronic memantine treatment also increased both sIPSC and mIPSC frequency and amplitude, suggestive of increased GABAergic transmission. Results suggest that a simple imbalance between glutamatergic and GABAergic neurotransmission may not underlie memantine’s ictogenic properties. That said, glutamatergic and GABAergic transmission were assayed independently of one another in the current study. More complex interactions between glutamatergic and GABAergic transmission may prevail under conditions of intact circuitry. PMID:24184417

Acceptance and Commitment Therapy in the Rehabilitation of a Girl with Chronic Idiopathic Pain: Are We Breaking New Ground?

ERIC Educational Resources Information Center

Asmundson, Gordon J. G.; Hadjistavropolous, Heather D.

2006-01-01

Wicksell and colleagues (2005) addressed the important and currently understudied realm of chronic idiopathic musculoskeletal pain treatment in children. They presented a brief overview of empirically supported treatments for children with chronic pain, detailed their case and intervention strategy, and offered conclusions regarding the potential…

Risk of chronic and end stage kidney disease in patients with nephrolithiasis.

PubMed

Shoag, Jonathan; Halpern, Joshua; Goldfarb, David S; Eisner, Brian H

2014-11-01

We examine kidney stone disease as a potential risk factor for chronic kidney disease, end stage kidney disease and treatment with dialysis. The NHANES (National Health and Nutrition Examination Survey) 2007-2010 database was interrogated for patients with a history of kidney stones. Demographics and comorbid conditions including age, gender, body mass index, diabetes, hemoglobin A1c, hypertension, gout and smoking were also assessed. Multivariate analysis adjusting for patient demographics and comorbidities was performed to assess differences in the prevalence of chronic kidney disease and treatment with dialysis between the 2 groups. History of nephrolithiasis was assessed with the question, "Have you ever had kidney stones?" Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) and/or a urinary albumin-to-creatinine ratio greater than 30 mg/gm. Statistical calculations were performed using Stata® software with determinations of p values and 95% CI where appropriate. The study included an analysis of 5,971 NHANES participants for whom data on chronic kidney disease and kidney stones were available, of whom 521 reported a history of kidney stones. On multivariate analysis a history of kidney stones was associated with chronic kidney disease and treatment with dialysis (OR 1.50, 1.10-2.04, p = 0.013 and OR 2.37, 1.13-4.96, p = 0.025, respectively). This difference appeared to be driven by women, where a history of kidney stones was associated with a higher prevalence of chronic kidney disease (OR 1.76, 1.13-2.763, p = 0.016) and treatment with dialysis (OR 3.26, 1.48-7.16, p = 0.004). There was not a significant association between kidney stone history and chronic kidney disease or treatment with dialysis in men. Kidney stone history is associated with an increased risk of chronic kidney disease and treatment with dialysis among women even after adjusting for comorbid conditions. Large scale prospective studies are needed to further characterize the relationship between nephrolithiasis and chronic kidney disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Application of saw palmetto fruit extract in the treatment of prostate diseases].

PubMed

Zhan, Xu-xin; Shang, Xue-jun; Huang, Yu-feng

2015-09-01

Saw palmetto fruit extract (SPE), as a herbal product, is widely used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Recent studies show that SPE also has some therapeutic effects on chronic prostatitis, prostate cancer, sexual dysfunction, and so on. This article presents an overview on the application of SPE in the treatment of BPH, prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome, with a discussion on its action mechanisms.

Saw palmetto and finasteride in the treatment of category-III prostatitis/chronic pelvic pain syndrome.

PubMed

Yang, Jennifer; Te, Alexis E

2005-07-01

Chronic nonbacterial prostatitis/chronic pelvic pain syndrome is a common entity for which a standardized management has not been established. Patients often have a significant symptom complex and impact on quality of life, but very little is known about the efficacy of second- and third-line treatments, such as the use of herbal supplements. Many treatments studied in recent literature include antibiotics, alpha-blockade, anti-inflammatory agents, and cognitive behavioral interventions such as biofeedback and psychotherapy.

Review of posttraumatic stress disorder and chronic pain: the path to integrated care.

PubMed

Gibson, Carri-Ann

2012-01-01

With the large number of Veterans experiencing posttraumatic stress disorder (PTSD) and chronic pain, the purpose of this article is to review the prevalence of PTSD and chronic pain, the theoretical models that explain the maintenance of both conditions, and the challenges faced by providers and families who care for these patients. The Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress with special attention to chronic pain is presented. Limited scientific evidence supports specific care and treatment of PTSD and chronic pain, and this challenges providers to investigate and research potential treatment options. Integrated care models designed for working with these patients are reviewed, including a focus on the techniques and strategies to address not only PTSD and chronic pain, but other conditions, including substance dependence and depression. A specific focus on headaches, back pain, and neuropathic pain follows, including treatment recommendations such as pharmacological, psychotherapeutic, and complementary approaches, given the high rates of these pain complaints for Veterans in PTSD clinical programs. Integrated care is presented as a viable solution and approach that challenges clinicians and researchers to develop innovative, scientifically based therapeutics and treatments to enhance the recovery and quality of life for Veterans with PTSD and chronic pain.

Rethinking chronic pain in a primary care setting.

PubMed

Stanos, Steven; Brodsky, Marina; Argoff, Charles; Clauw, Daniel J; D'Arcy, Yvonne; Donevan, Sean; Gebke, Kevin B; Jensen, Mark P; Lewis Clark, Evelyn; McCarberg, Bill; Park, Peter W; Turk, Dennis C; Watt, Stephen

2016-06-01

Chronic pain substantially impacts patient function and quality of life and is a burden to society at large in terms of increased health care utilization and loss of productivity. As a result, there is an increasing recognition of chronic pain as a public health crisis. However, there remains wide variability in clinical practices related to the prevention, assessment, and treatment of chronic pain. Certain fundamental aspects of chronic pain are often neglected including the contribution of the psychological, social, and contextual factors associated with chronic pain. Also commonly overlooked is the importance of understanding the likely neurobiological mechanism(s) of the presenting pain and how they can guide treatment selection. Finally, physicians may not recognize the value of using electronic medical records to systematically capture data on pain and its impact on mood, function, and sleep. Such data can be used to monitor onset and maintenance of treatments effects at the patient level and evaluate costs at the systems level. In this review we explain how these factors play a critical role in the development of a coordinated, evidence-based treatment approach tailored to meet specific needs of the patient. We also discuss some practical approaches and techniques that can be implemented by clinicians in order to enhance the assessment and management of individuals with chronic pain in primary care settings.

Pharmacokinetic interactions of herbal medicines for the treatment of chronic hepatitis.

PubMed

Hsueh, Tun-Pin; Lin, Wan-Ling; Tsai, Tung-Hu

2017-04-01

Chronic liver disease is a serious global health problem, and an increasing number of patients are seeking alternative medicines or complementary treatment. Herbal medicines account for 16.8% of patients with chronic liver disease who use complementary and alternative therapies. A survey of the National Health Insurance Research Database in Taiwan reported that Long-Dan-Xie-Gan-Tang, Jia-Wei-Xia-Yao-San, and Xiao-Chai-Hu-Tang (Sho-saiko-to) were the most frequent formula prescriptions for chronic hepatitis used by traditional Chinese medicine physicians. Bioanalytical methods of herbal medicines for the treatment of chronic hepatitis were developed to investigate pharmacokinetics properties, but multicomponent herbal formulas have been seldom discussed. The pharmacokinetics of herbal formulas is closely related to efficacy, efficiency, and patient safety of traditional herbal medicines. Potential herbal formula-drug interactions are another essential issue during herbal formula administration in chronic hepatitis patients. In a survey with the PubMed database, this review article evaluates the existing evidence-based data associated with the documented pharmacokinetics profiles and potential herbal-drug interactions of herbal formulas for the treatment of chronic hepatitis. In addition, the existing pharmacokinetic profiles were further linked with clinical practice to provide insight for the safety and specific use of traditional herbal medicines. Copyright © 2016. Published by Elsevier B.V.

Extracorporeal shock wave treatment for chronic rotator cuff tendonitis (shoulder pain).

PubMed

Ho, C

2007-01-01

(1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic rotator cuff tendonitis (shoulder pain). The acoustic waves may help to accelerate the healing process of chronic rotator cuff tendonitis via an unknown mechanism. (2) ESWT, which is performed as an outpatient procedure, is intended to alleviate the pain due to chronic rotator cuff tendonitis. (3) Limited evidence from a German study indicates that the cost of ESWT for rotator cuff tendonitis is one-fifth to one-seventh the cost of surgical treatment, with longer recovery time and time off work in the surgical treatment group accounting for about two-thirds of the overall cost. (4) The evidence reviewed for this bulletin supports the use of high-energy ESWT for chronic calcific rotator cuff tendonitis, but not for non-calcific rotator cuff tendonitis. High-quality RCTs with larger sample sizes are needed to provide stronger evidence.

Common Questions About Chronic Prostatitis.

PubMed

Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

2016-02-15

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Sinonasal tumor in 3 dogs after successful topical treatment for frontal sinus aspergillosis

PubMed Central

Greci, Valentina; Stefanello, Damiano; Di Giancamillo, Mauro; Mortellaro, Carlo M.

2009-01-01

Three dogs diagnosed with aspergillosis developed sinonasal tumors several months after successful treatment with topical clotrimazole solution. Chronic rhinosinusitis was also detected in all cases prior to diagnosis of sinonasal tumors. The inflammatory response to Aspergillus, clotrimazole treatment, and chronic inflammation after treatment are discussed as possible neoplastic promoting factors. PMID:20119545

The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

PubMed Central

2012-01-01

Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway. PMID:22920325

An investigation of constructions of justice and injustice in chronic pain: a Q-methodology approach.

PubMed

McParland, Joanna; Hezseltine, Louisa; Serpell, Michael; Eccleston, Christopher; Stenner, Paul

2011-09-01

This study used Q-methodology to explore justice-related accounts of chronic pain. Eighty participants completed the Q-sorting procedure (33 chronic pain sufferers and 47 non-pain sufferers). Analysis revealed five main factors. Three factors blame: society for poor medical and interpersonal treatment; the chronic pain sufferer for indulging in self-pity and unempathic healthcare workers for ignoring patients. A fourth factor acknowledges the unfairness of pain and encourages self-reliance. The fifth factor rejects injustice in the chronic pain discourse. Overall, there is a shared view that chronic pain brings unfair treatment, disrespect and a de-legitimization of pain. Future research ideas are suggested.

[Factors that influence treatment adherence in chronic disease patients undergoing hemodialysis].

PubMed

Maldaner, Cláudia Regina; Beuter, Margrid; Brondani, Cecília Maria; Budó, Maria de Lourdes Denardin; Pauletto, Macilene Regina

2008-12-01

The following bibliographical research wanted to identify the main factors that influence adherence to treatment in chronic disease. The study focused on patients undergoing hemodialysis, as well as on the support nurses require for the promotion of health education among individuals with low treatment adherence. The identification of bibliographical sources was conducted at Health Virtual Library and Scientific Electronic Library Online (SciELO) data bases. Some printed magazines were also used. The results indicated nine factors influencing treatment adherence or non-adherence: team trust, support nets, educational level; accepting disease, treatment side effects, lack of access to medicines, long-term treatment, complex therapeutic approach, and lack of symptoms. It is advisable that nurses take into account these factors when dealing with chronic-disease patients that present low treatment adherence, getting family and multidisciplinary team support seeking treatment adherence.

Update on Postnatal Steroids.

PubMed

Halliday, Henry L

2017-01-01

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention. © 2017 S. Karger AG, Basel.

The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study.

PubMed

Lin, Tsai-Hui; Yen, Hung-Rong; Chiang, Jen-Huai; Sun, Mao-Feng; Chang, Hen-Hong; Huang, Sheng-Teng

2017-04-18

There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38-0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic hepatitis among colon cancer patients. This nationwide retrospective cohort study determined that therapy using CHM as an adjuvant modality may have a significant impact on liver protection in patients with colon cancer. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Deciding in the dark: advance directives and continuation of treatment in chronic critical illness.

PubMed

Camhi, Sharon L; Mercado, Alice F; Morrison, R Sean; Du, Qingling; Platt, David M; August, Gary I; Nelson, Judith E

2009-03-01

Chronic critical illness is a devastating syndrome for which treatment offers limited clinical benefit but imposes heavy burdens on patients, families, clinicians, and the health care system. We studied the availability of advance directives and appropriate surrogates to guide decisions about life-sustaining treatment for the chronically critically ill and the extent and timing of treatment limitation. Prospective cohort study. Respiratory Care Unit (RCU) in a large, tertiary, urban, university-affiliated, hospital. Two hundred three chronically critically ill adults transferred to RCU after tracheotomy for failure to wean from mechanical ventilation in the intensive care unit. None. We interviewed RCU caregivers and reviewed patient records to identify proxy appointments, living wills, or oral statements of treatment preferences, resuscitation directives, and withholding/withdrawal of mechanical ventilation, nutrition, hydration, renal replacement and vasopressors. Forty-three of 203 patients (21.2%) appointed a proxy and 33 (16.2%) expressed preferences in advance directives. Do not resuscitate directives were given for 71 patients (35.0%). Treatment was limited for 39 patients (19.2%). Variables significantly associated with treatment limitation were proxy appointment prior to study entry (time of tracheotomy/RCU transfer) (odds ratio = 6.7, 95% confidence interval [CI], 2.3-20.0, p = 0.0006) and palliative care consultation in the RCU (OR = 40.9, 95% CI, 13.1-127.4, p < 0.0001). Median (interquartile range) time to first treatment limitation was 39 (31.0-45.0) days after hospital admission and 13 (8.0-29.0) days after RCU admission. For patients dying after treatment limitation, median time from first limitation to death ranged from 3 days for mechanical ventilation and hydration to 7 days for renal replacement. Most chronically critically ill patients fail to designate a surrogate decision-maker or express preferences regarding life-sustaining treatments. Despite burdensome symptoms and poor outcomes, limitation of such treatments was rare and occurred late, when patients were near death. Opportunities exist to improve communication and decision-making in chronic critical illness.

Pulsed radiofrequency treatment of articular branches of femoral and obturator nerves for chronic hip pain.

PubMed

Chye, Cien-Leong; Liang, Cheng-Loong; Lu, Kang; Chen, Ya-Wen; Liliang, Po-Chou

2015-01-01

Chronic hip pain is a common symptom experienced by many people. Often, surgery is not an option for patients with multiple comorbidities, and conventional drugs either have many side effects or are ineffective. Pulsed radiofrequency (PRF) is a new method in the treatment of pain. We attempt to compare the efficacy of PRF relative to conservative management for chronic hip pain. Between August 2011 and July 2013, 29 patients with chronic hip pain were divided into two groups (PRF and conservative treatment) according to consent or refusal to undergo PRF procedure. Fifteen patients received PRF of the articular branches of the femoral and obturator nerves, and 14 patients received conservative treatment. Visual analog scale (VAS), Oxford hip scores (OHS), and pain medications were used for outcome measurement before treatment and at 1 week, 4 weeks, and 12 weeks after treatment. At 1 week, 4 weeks, and 12 weeks after treatment initiation, improvements in VAS were significantly greater with PRF. Improvements in OHS were significantly greater in the PRF group at 1 week, 4 weeks, and 12 weeks. Patients in the PRF group also used less pain medications. Eight subjects in the conservative treatment group switched to the PRF group after 12 weeks, and six of them had >50% improvement. When compared with conservative treatment, PRF of the articular branches of the femoral and obturator nerves offers greater pain relief for chronic hip pain and can augment physical functioning.

[Combined physiotherapy of chronic infectious prostatitis].

PubMed

Churakov, A A; Popkov, V M; Zemskov, S P; Glybochko, P V; Bliumberg, B I

2007-01-01

Our experience with therapy of 259 outpatients with chronic infectious prostatitis (CIP) aged 16-55 years has demonstrated that combined treatment of CIP with rectal digital massage of the prostate, electrophoresis of chimotripsin solution with dimexide and local magnetotherapy (Intramag unit) significantly raises treatment efficacy, shortens treatment, prevents complications.

Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Willner, Paul

2017-02-01

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

[Extracorporeal shock wave therapy in chronic prostatitis].

PubMed

Kul'chavenya, E V; Shevchenko, S Yu; Brizhatyuk, E V

2016-04-01

Chronic prostatitis is a prevalent urologic disease, but treatment outcomes are not always satisfactory. As a rule, chronic prostatitis results in chronic pelvic pain syndrome, significantly reducing the patient's quality of life. Open pilot prospective non-comparative study was conducted to test the effectiveness of extracorporeal shock wave therapy (ESWT) using Aries (Dornier) machine in patients with chronic prostatitis (CP) of IIIb category. A total of 27 patients underwent ESWL as monotherapy, 2 times a week for a course of 6 sessions. Exposure settings: 5-6 energy level (by sensation), the frequency of 5 Hz, 2000 pulses per session; each patient received a total energy up to 12000 mJ. per procedure. Treatment results were evaluated using NIH-CPSI (National Institute of Health Chronic Prostatitis Symptom Index) upon completing the 3 week course of 6 treatments and at 1 month after ESWT. Immediately after the ESWT course positive trend was not significant: pain index decreased from 9.1 to 7.9, urinary symptom score remained almost unchanged (4.2 at baseline, 4.1 after treatment), quality of life index also showed a slight improvement, dropping from 7.2 points to 6.0. Total NIH-CPSI score decreased from 20.5 to 18.0. One month post-treatment pain significantly decreased to 3.2 points, the urinary symptom score fell to 2.7 points, the average quality of life score was 3.9 points. ESWT, performed on Aries (Dornier) machine, is highly effective as monotherapy in patients with category IIIb chronic prostatitis.

Conversion Disorder, Functional Neurological Symptom Disorder, and Chronic Pain: Comorbidity, Assessment, and Treatment.

PubMed

Tsui, Patricia; Deptula, Andrew; Yuan, Derek Y

2017-06-01

This paper examines the overlap of conversion disorder with chronic pain conditions, describes ways to assess for conversion disorder, and provides an overview of evidence-based treatments for conversion disorder and chronic pain, with a focus on conversion symptoms. Conversion disorder is a significant problem that warrants further study, given that there are not many well-established guidelines. Accurate and timely assessment should help move treatment in a more fruitful direction and avoid unnecessary medical interventions. Advances in neuroimaging may also help further our understanding of conversion disorder. Creating a supportive environment and a collaborative treatment relationship and improving understanding of conversion symptoms appear to help individuals diagnosed with conversion disorder engage in appropriate treatments. Novel uses of earlier treatments, such as hypnosis and psychodynamic approaches, could potentially be beneficial and require a more vigorous and systematic study. There are treatments that produce significant improvements in functioning and reduction of physical symptoms from conversion disorder even for very severe cases. Hypnotherapy, cognitive behavioral therapy, and inpatient multidisciplinary treatment with intensive physiotherapy for severe cases have the most evidence to support reduction of symptoms. Components of treatment for conversion disorder overlap with treatments for chronic pain and can be used together to produce therapeutic effects for both conditions. Treatment needs to be tailored for each individual's specific symptoms.

[Effects of diazepam on mixed anxiety/depression state in male mice].

PubMed

Galiamina, A G; Smagin, D A; Kovalenko, I L; Bondar', N P; Kudriavtseva, N N

2013-11-01

Chronic social defeat stress in daily agonistic interactions leads to the development of mixed anxiety/depression state in male mice. This paper aimed to study the effects of chronic diazepam treatment on the psychoemotional state of these animals. Diazepam (0.5 mg/kg, i/p, Polfa Tarchomin S. A.) or saline was chronically injected into male mice for two weeks on the background of continuing agonistic interactions (preventive treatment) or into male mice with mixed anxiety/depression state after stopping of social confrontations (therapeutic treatment). Then, the animals were studied in the partition, plus-maze and Porsolt' tests, estimating the levels of communicativeness, anxiety and depressiveness, respectively. Preventive diazepam treatment had a weak protective anxiolytic and pro-depressive effect. The therapeutic diazepam treatment didn't influence on the anxiety and depression-like state. Chronic diazepam was ineffective for the treatment of the mixed anxiety/depression state in male mice. Different effects ofdiazepam on anxiety and depression-like states under preventive treatment confirmed our conclusion shown earlier about the independent development of these pathologies at least in our experimental paradigm.

Smoking, chronic wound healing, and implications for evidence-based practice.

PubMed

McDaniel, Jodi C; Browning, Kristine K

2014-01-01

Chronic wounds are rising in prevalence and creating significant socioeconomic burdens for patients and healthcare systems worldwide. Therefore, it is now more important than ever that clinicians follow evidence-based guidelines for wound care when developing personalized treatment plans for their patients with chronic wounds. Evidence-based guidelines for treating venous leg ulcers, diabetic foot ulcers, and pressure ulcers, the 3 main categories of chronic wounds, focus primarily on biologic therapies. However, there are also evidence-based guidelines for treating behavioral risks to poor healing, such as smoking, which should be incorporated into treatment plans when appropriate. The purpose of this article was to review the mechanisms through which smoking adversely impacts the wound healing process, and propose strategies for incorporating evidence-based guidelines for treating tobacco dependence into treatment plans for patients with chronic wounds who smoke.

The Efficacy of Systemic Lidocaine in the Management of Chronic Pain: A Literature Review.

PubMed

Yousefshahi, Fardin; Predescu, Oana; Francisco Asenjo, Juan

2017-06-01

Despite recent advances in the understanding of the chronic pain concept, its diagnosis and management remains a daily challenge for clinicians and patients. Based on the published literature, this review discusses and tries to organize the current knowledge and the up-to-date clinical experience about the efficacy and safety of the use of intravenous lidocaine in treatment and prevention of chronic pain. To prepare this narrative review, we performed an in depth literature review using the PubMed searching engine. We extracted all relevant articles published in English, up to April 2016. Lidocaine, administered as transdermal patch or intravenous lidocaine, is a safe and effective modality in the treatment of post-herpetic neuralgia (PHN), complex regional pain syndrome, as well and for prevention of chronic pain. It may be effective in the management of neuropathic pain syndromes, chronic pain, post-operative pain, and refractory cancer pain. Intravenous lidocaine and lidocaine patch are effective and safe for the treatment of several chronic or neuropathic pain syndromes. The use of lidocaine during surgery could prevent the development of some chronic post-surgical pain syndromes.

Tuberculosis associated chronic obstructive pulmonary disease.

PubMed

Sarkar, Malay; Srinivasa; Madabhavi, Irappa; Kumar, Kushal

2017-05-01

Reviewed the epidemiology, clinical characteristics, mechanisms, and treatment of tuberculosis associated chronic obstructive pulmonary disease. We searched PubMed, EMBASE, and the CINAHL from inception to June 2016. We used the following search terms: Tuberculosis, COPD, Tuberculosis associated COPD, and so forth. All types of study were chosen. Chronic obstructive pulmonary disease (COPD) and tuberculosis are significant public health problems, particularly in developing countries. Although, smoking is the conventional risk factor for COPD, nonsmoking related risk factors such as biomass fuel exposure, childhood lower-respiratory tract infections, chronic asthma, outdoor air pollution, and prior history of pulmonary tuberculosis have become important risk factors of COPD, particularly in developing countries. Past history of tuberculosis as a risk factor of chronic airflow obstruction has been reported in several studies. It may develop during the course of tuberculosis or after completion of tuberculosis treatment. Developing countries with large burden of tuberculosis can contribute significantly to the burden of chronic airflow obstruction. Prompt diagnosis and treatment of tuberculosis should be emphasized to lessen the future burden of chronic airflow obstruction. © 2017 John Wiley & Sons Ltd.

Older people's experiences of patient-centered treatment for chronic pain: a qualitative study.

PubMed

Teh, Carrie F; Karp, Jordan F; Kleinman, Arthur; Reynolds Iii, Charles F; Weiner, Debra K; Cleary, Paul D

2009-04-01

Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient-provider relationship. In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient-provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient-provider relationship is important to this population. Specifically, participants described the importance of "being heard" and "being understood" by providers. As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient-provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient-provider relationship by attending to differences in patients' willingness to engage in patient-directed care and emphasizing shared decision-making.

The role of insomnia in the treatment of chronic fatigue.

PubMed

Kallestad, Håvard; Jacobsen, Henrik B; Landrø, Nils Inge; Borchgrevink, Petter C; Stiles, Tore C

2015-05-01

The definition of Chronic Fatigue Syndrome (CFS) overlaps with definitions of insomnia, but there is limited knowledge about the role of insomnia in the treatment of chronic fatigue. To test if improvement of insomnia during treatment of chronic fatigue was associated with improved outcomes on 1) fatigue and 2) cortisol recovery span during a standardized stress exposure. Patients (n = 122) with chronic fatigue received a 3.5-week inpatient return-to-work rehabilitation program based on Acceptance and Commitment Therapy, and had been on paid sick leave>8 weeks due their condition. A physician and a psychologist examined the patients, assessed medication use, and SCID-I diagnoses. Patients completed self-report questionnaires measuring fatigue, pain, depression, anxiety, and insomnia before and after treatment. A subgroup (n = 25) also completed the Trier Social Stress Test for Groups (TSST-G) before and after treatment. Seven cortisol samples were collected during each test and cortisol spans for the TSST-G were calculated. A hierarchical regression analysis in nine steps showed that insomnia improvement predicted improvement in fatigue, independently of age, gender, improvement in pain intensity, depression and anxiety. A second hierarchical regression analysis showed that improvement in insomnia significantly predicted the cortisol recovery span after the TSST-G independently of improvement in fatigue. Improvement in insomnia severity had a significant impact on both improvement in fatigue and the ability to recover from a stressful situation. Insomnia severity may be a maintaining factor in chronic fatigue and specifically targeting this in treatment could increase treatment response. Copyright © 2014. Published by Elsevier Inc.

Update on the use of alitretinoin in treating chronic hand eczema.

PubMed

Ghasri, Pedram; Scheinfeld, Noah

2010-04-19

Chronic hand eczema is a debilitating dermatological condition with significant economic, social, and functional impacts. To date, conventional treatments such as topical corticosteroids, phototherapy, and systemic immunosuppressants have yielded disappointing results, owing to either a lack of efficacy or significant adverse events. Oral alitretinoin (9-cis-retinoic acid) is a unique panagonist retinoid with immunomodulatory and anti-inflammatory activity that has emerged as a novel treatment for chronic hand eczema. Several large-scale clinical studies have demonstrated oral alitretinoin's high efficacy rate of 28% to 89%, its safe tolerability profile, and its positive impact on quality of life, validating it as a therapeutic option for patients with severe chronic hand eczema refractory to standard treatment.

Constipation: evaluation and treatment of colonic and anorectal motility disorders.

PubMed

Rao, Satish S C

2007-09-01

This article focuses on the colonic and anorectal motility disturbances that are associated with chronic constipation and their management. Functional chronic constipation consists of three overlapping subtypes: slow transit constipation, dyssynergic defecation, and irritable bowel syndrome with constipation. The Rome criteria may serve as a useful guide for making a clinical diagnosis of functional constipation. Today, an evidence-based approach can be used to treat patients with chronic constipation. The availability of specific drugs for the treatment of chronic constipation, such as tegaserod and lubiprostone, has enhanced the therapeutic armamentarium for managing these patients. Randomized controlled trials have also established the efficacy of biofeedback therapy in the treatment of dyssynergic defecation.

A meta-analysis of hypnosis for chronic pain problems: a comparison between hypnosis, standard care, and other psychological interventions.

PubMed

Adachi, Tomonori; Fujino, Haruo; Nakae, Aya; Mashimo, Takashi; Sasaki, Jun

2014-01-01

Hypnosis is regarded as an effective treatment for psychological and physical ailments. However, its efficacy as a strategy for managing chronic pain has not been assessed through meta-analytical methods. The objective of the current study was to conduct a meta-analysis to assess the efficacy of hypnosis for managing chronic pain. When compared with standard care, hypnosis provided moderate treatment benefit. Hypnosis also showed a moderate superior effect as compared to other psychological interventions for a nonheadache group. The results suggest that hypnosis is efficacious for managing chronic pain. Given that large heterogeneity among the included studies was identified, the nature of hypnosis treatment is further discussed.

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

PubMed Central

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-01-01

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects.

PubMed

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-12-02

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

Treatment of a Case Example with PTSD and Chronic Pain

ERIC Educational Resources Information Center

Shipherd, Jillian C.

2006-01-01

This commentary reviews the case of GH, a survivor of a road traffic collision, who has chronic pain and posttraumatic stress disorder (PTSD). The case formulation, assessment strategy, and treatment plan are informed by the relevant experimental literature and empirically supported treatments using a cognitive behavioral perspective. Given this…

Familiarizing Students with the Empirically Supported Treatment Approaches for Psychophysiological Disorders and Chronic Pain.

ERIC Educational Resources Information Center

Wilkins, Victoria; Chambliss, Catherine

In training counseling students, it is increasingly important to acquaint them with the clinical research literature exploring the efficacy of particular treatments. This review of empirically supported treatments (EST's) concerning psychophysiological disorders and chronic pain is intended to facilitate the educational process. EST's, or…

Family-Based Cognitive-Behavioral Treatment of Chronic Pediatric Headache and Anxiety Disorders: A Case Study

ERIC Educational Resources Information Center

Drake, Kelly L.; Ginsburg, Golda S.

2012-01-01

Background: Chronic pediatric headache disorders are pervasive, debilitating, and associated with high rates of comorbid anxiety disorders. The combination of headaches and anxiety presents unique challenges for clinicians. Cognitive behavioral therapy (CBT) is a promising treatment for pediatric headache, however, available treatments fail to…

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... Kidney Disease Anemia in Chronic Kidney Disease Financial Help for Treatment of Kidney Failure Learning as much as you can about your treatment will help make you an important member of your health ...

Endoscopic Therapies for Chronic Pancreatitis.

PubMed

Adler, Jeffrey M; Gardner, Timothy B

2017-07-01

Chronic pancreatitis is a fibroinflammatory disease of the pancreas leading to varying degrees of endocrine and exocrine dysfunction. Treatment options are generally designed to control the pain of chronic pancreatitis, and endoscopic therapy is one of the main treatment modalities. Herein, we describe the endoscopic management of pancreatic duct calculi and strictures, entrapment of the intrapancreatic bile duct, celiac plexus interventions, and drainage of pancreatic pseudocysts.

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

PubMed Central

Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

2005-01-01

AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B. PMID:16437674

Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.

PubMed

Roitman, Pablo; Mechoulam, Raphael; Cooper-Kazaz, Rena; Shalev, Arieh

2014-08-01

Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ(9)-tetrahydrocannabinol (THC) for chronic PTSD. Ten outpatients with chronic PTSD, on stable medication, received 5 mg of Δ(9)-THC twice a day as add-on treatment. There were mild adverse effects in three patients, none of which led to treatment discontinuation. The intervention caused a statistically significant improvement in global symptom severity, sleep quality, frequency of nightmares, and PTSD hyperarousal symptoms. Orally absorbable Δ(9)-THC was safe and well tolerated by patients with chronic PTSD.

Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain.

PubMed

Aronson, M D

1997-01-01

The treatment of chronic pain is an important function of physicians. In the United States, available drug treatments for chronic pain currently include simple analgesics such as acetaminophen, salicylates and other nonsteroidal anti-inflammatory drugs, traditional opioid drugs, and adjuvant agents (eg, antidepressants, anticonvulsants). Typically, the choice of a drug is made by balancing the indications for treatment, the clinical efficacy of the drug, and its toxicity. An understanding of the mechanism of action of these drugs helps to establish their role in therapy. Tramadol is an effective analgesic that works through a combined mechanism of weak mu receptor binding and the inhibition of serotonin and norepinephrine reuptake. Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes.

Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

PubMed Central

Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

2012-01-01

Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa].

PubMed

Schwarz, C; Schulte-Hubbert, B; Bend, J; Abele-Horn, M; Baumann, I; Bremer, W; Brunsmann, F; Dieninghoff, D; Eickmeier, O; Ellemunter, H; Fischer, R; Grosse-Onnebrink, J; Hammermann, J; Hebestreit, H; Hogardt, M; Hügel, C; Hug, M; Illing, S; Jung, A; Kahl, B; Koitschev, A; Mahlberg, R; Mainz, J G; Mattner, F; Mehl, A; Möller, A; Muche-Borowski, C; Nüßlein, T; Puderbach, M; Renner, S; Rietschel, E; Ringshausen, F C; Schmidt, S; Sedlacek, L; Sitter, H; Smaczny, C; Tümmler, B; Vonberg, R; Wielpütz, M O; Wilkens, H; Wollschläger, B; Zerlik, J; Düesberg, U; van Koningsbruggen-Rietschel, S

2018-05-01

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa ( Pa ) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa -infection. This is a S3-clinical guideline which implements a definition for chronic Pa -infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa -infection in order to give guidance for individual treatment options. © Georg Thieme Verlag KG Stuttgart · New York.

An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

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

Pauly, J.R.; Marks, M.J.; Gross, S.D.

1991-09-01

Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the numbermore » of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.« less

The proteins interacting with C-terminal of μ receptor are identified by bacterial two-hybrid system from brain cDNA library in morphine-dependent rats.

PubMed

Zhou, Peilan; Jiang, Jiebing; Dong, Zhaoqi; Yan, Hui; You, Zhendong; Su, Ruibin; Gong, Zehui

2015-12-15

Opioid addiction is associated with long-term adaptive changes in the brain that involve protein expression. The carboxyl-terminal of the μ opioid receptor (MOR-C) is important for receptor signal transduction under opioid treatment. However, the proteins that interact with MOR-C after chronic morphine exposure remain unknown. The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study. The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART (Switching Mechanism At 5' end of RNA Transcript) technique. Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library. RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment. Column overlay assays, immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor (NADE). 21 positive proteins, including 19 known proteins were screened to interact with rat MOR-C. Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment. Among these proteins, NADE was confirmed to interact with rat MOR-C by in vitro protein-protein binding and coimmunoprecipitation in Chinese hamster ovary (CHO) cells and rat brain with or without chronic morphine treatment. Understanding the rat MOR-C interacting proteins and the proteins variation under chronic morphine treatment may be critical for determining the pathophysiological basis of opioid tolerance and addiction. Copyright © 2015. Published by Elsevier Inc.

5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats.

PubMed

Sukoff Rizzo, Stacey J; Pulicicchio, Claudine; Malberg, Jessica E; Andree, Terrance H; Stack, Gary P; Hughes, Zoë A; Schechter, Lee E; Rosenzweig-Lipson, Sharon

2009-09-01

Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapies. 5-HT(1A) antagonists have been suggested as beneficial adjunctive treatment in respect of antidepressant efficacy; however, the effects of 5-HT(1A) antagonism on antidepressant-induced side-effects has not been fully examined. The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT(1A) antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls. Acute administration of the 5-HT(1A) antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines. Chronic co-administration of the 5-HT(1A) antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats. Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT(1A) antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT(1A) antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.

Chronic treatment with fluoxetine modulates vascular adrenergic responses by inhibition of pre- and post-synaptic mechanisms.

PubMed

Pereira, Camila A; Rodrigues, Fernanda L; Ruginsk, Silvia G; Zanotto, Camila Z; Rodrigues, José A; Duarte, Diego A; Costa-Neto, Claudio M; Resstel, Leonardo B; Carneiro, Fernando S; Tostes, Rita C

2017-04-05

Fluoxetine, a serotonin reuptake inhibitor (SSRI), has other effects in addition to blocking serotonin reuptake, including changes in the vasomotor tone. Whereas many studies focused on the acute effects of fluoxetine in the vasculature, its chronic effects are still limited. In the present study, we tested the hypothesis that chronic fluoxetine treatment modulates adrenergic vascular responses by interfering with post- and pre-synaptic mechanisms. Wistar rats were treated with vehicle (water) or chronic fluoxetine (10mg/kg/day) for 21 days. Blood pressure (BP) and heart rate were measured. Vascular reactivity was evaluated in perfused mesenteric arterial beds (MAB) and in mesenteric resistance arteries. Protein expression by western blot analysis or immunohistochemistry, β-arrestin recruitment by BRET and calcium influx by FLIPR assay. Fluoxetine treatment decreased phenylephrine (PE)-induced, but not electrical-field stimulation (EFS)-induced vasoconstriction. Fluoxetine-treated rats exhibited increased KCl-induced vasoconstriction, which was abolished by prazosin. Desipramine, an inhibitor of norepinephrine (NA) reuptake, increased EFS-induced vasoconstrictor response in vehicle-treated, but not in fluoxetine-treated rats. Chronic treatment did not alter vascular expression of α 1 adrenoceptor, phosphorylation of PKCα or ERK 1/2 and RhoA. On the other hand, vascular contractions to calcium (Ca 2+ ) as well as Ca 2+ influx in mesenteric arteries were increased, while intracellular Ca 2+ storage was decreased by the chronic treatment with fluoxetine. In vitro, fluoxetine decreased vascular contractions to PE, EFS and Ca 2+ , but did not change β-arrestin activity. In conclusion, chronic treatment with fluoxetine decreases sympathetic-mediated vascular responses by mechanisms that involve inhibition of NA release/reuptake and decreased Ca 2+ stores. Copyright © 2017 Elsevier B.V. All rights reserved.

Bosutinib: a review of its use in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

PubMed

Syed, Yahiya Y; McCormack, Paul L; Plosker, Greg L

2014-02-01

Bosutinib (Bosulif®) is an orally administered small molecule tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC family kinases. It is indicated for the treatment of adult patients with chronic-, accelerated-, or blast-phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy (imatinib, dasatinib, or nilotinib) [USA] or for a small subpopulation of these patients for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options (EU). In a multinational pivotal trial (n = 547), bosutinib treatment resulted in a major cytogenetic response (MCyR) at 24 weeks in one-third of all treated patients with imatinib-resistant chronic-phase CML who had no previous exposure to any TKIs other than imatinib (primary endpoint), with similar results observed in chronic-phase CML patients who were intolerant of imatinib and naïve to all other TKIs. MCyRs were also seen in more than one-quarter of evaluable patients with chronic-phase CML previously treated with multiple TKIs. Most of the patients with chronic-phase CML achieved a complete hematologic response with bosutinib and some patients with advanced phases of CML achieved an overall hematologic response. Responses were seen irrespective of the type of BCR-ABL mutation at baseline, except T315I. Bosutinib had a manageable tolerability profile in the pivotal trial, with ≤21 % of patients with chronic-phase CML discontinuing the treatment because of adverse events. Diarrhea was the most common adverse event but was generally manageable, with only few patients discontinuing the treatment because of diarrhea. Therefore, bosutinib is a useful TKI option for patients with Ph+ CML in second-line or greater settings.

Chronic urinary tract infections in patients with spinal cord lesions - biofilm infection with need for long-term antibiotic treatment.

PubMed

Tofte, Nete; Nielsen, Alex C Y; Trøstrup, Hannah; Andersen, Christine B; Von Linstow, Michael; Hansen, Birgitte; Biering-Sørensen, Fin; Høiby, Niels; Moser, Claus

2017-04-01

Patients suffering from spinal cord injuries resulting in complete or incomplete paraplegia or tetraplegia are highly disposed to frequent, recurrent or even chronic urinary tract infections (UTIs). The reason for the increased risk of acquiring UTIs is multifactorial, including reduced sensation of classical UTI symptoms, incomplete bladder emptying, frequent catheterizations or chronic urinary tract catheters. Biofilms in relation to UTIs have been shown both on catheters, on concrements or as intracellular bacterial communities (IBCs). Due to the increased risk of acquiring recurrent or chronic UTIs and frequent antibiotic treatments, patients experience an increased risk of being infected with antibiotic-resistant bacteria like extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella spp., but also bacteria like Pseudomonas aeruginosa inherently resistant to several antibiotics. Diagnosing the UTI can also be challenging, especially distinguishing harmless colonization from pathogenic infection. Based on a previous study showing activation of humoral immune response toward UTI pathogens in patients with spinal cord lesions (SCL), the present mini review is an evaluation of using antibody response as an indicator of chronic biofilm UTI. In addition, we evaluated the effect of long-term treatment with antibiotics in patients with SCLs and chronic UTI, defined by culturing of a uropathogen in the urine and elevated specific precipitating antibodies against the same uropathogen in a blood sample. Elimination of chronic UTI, decrease in specific precipitating antibody values and avoiding selection of new multidrug-resistant (MDR) uropathogens were the primary markers for effect of treatment. The results of this evaluation suggest that the long-term treatment strategy in SCL patients with chronic UTI may be effective; however, randomized prospective results are needed to confirm this. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Sleep America: managing the crisis of adult chronic insomnia and associated conditions.

PubMed

Kraus, Stefanie S; Rabin, Laura A

2012-05-01

Chronic insomnia, a public health crisis affecting 10-15% of the U.S. population and costing billions of dollars annually, typically presents with one or more comorbid psychiatric or organic conditions. Historical classification of chronic insomnia as "secondary" to a presenting comorbid condition has resulted in under-recognition and under-treatment of both the insomnia and comorbid condition(s). Though critical in any model of comorbid disease management, chronic insomnia receives little, if any, public policy attention. We conducted a systematic review of recent empirical studies, review papers, books, government documents, press releases, advertisements, and articles pertaining to the classification, epidemiology, treatment, and physiology of sleep, insomnia, and comorbid conditions. Data were located primarily through MEDLINE, PsycINFO, SCOPUS, and PUBMED databases. Our goal was to provide an overview of the systems for classifying insomnia and available epidemiological data, and to review theoretical models regarding the etiology and maintaining factors of chronic insomnia along with research on the complex, bidirectional associations between chronic insomnia and various affective (and other) conditions. After thorough review of the literature, we propose several public policy measures as an initial step in managing chronic insomnia in the United States. These include introducing a nation-wide multi-modal educational and awareness campaign titled "Sleep America;" increasing the availability and demand for behavioral sleep medicine - the initially preferred treatment approach; and increasing the use of monitoring and enforcement activities by regulatory authorities to curtail false and misleading claims by sponsors of supplements or treatments for insomnia. Through the adoption of such measures, we hope to galvanize a national interest in healthy sleep and the evidence-based treatment of chronic insomnia. Copyright © 2011 Elsevier B.V. All rights reserved.

Ghrelin and cachexia: will treatment with GHSR-1a agonists make a difference for patients suffering from chronic wasting syndromes?

PubMed

DeBoer, Mark D

2011-06-20

Cachexia is a syndrome of wasting and anorexia that worsens the prognosis of many chronic diseases including cancer, chronic kidney disease, chronic heart disease and chronic obstructive pulmonary disease. Properties of the orexigenic hormone ghrelin-including appetite-stimulation, weight-gain production and increased cardiac output make it a logical treatment for cachexia. While endogenous ghrelin levels are increased in the setting of cachexia, treatment with ghrelin and other GHSR-1a agonists in animal models of cachexia and in humans with cachexia has demonstrated consistent effects of increased appetite and improved weight gain. These positive effects occur in multiple underlying diseases associated with cachexia and appear to be sustained over treatment duration of up to 12 weeks. The mechanism of action in producing these effects is likely related to stimulation of central appetite centers such as the central melanocortin system and to increased growth hormone release, though ghrelin's effects may also relate to decreased systemic inflammation and other direct and indirect actions. Questions regarding the long-term safety of ghrelin treatment are still unanswered, as is the important question of whether successful treatment of cachexia will improve the prognosis of the underlying disease itself. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ghrelin and cachexia: Will treatment with GHSR-1a agonists make a difference for patients suffering from chronic wasting syndromes?

PubMed Central

DeBoer, Mark D.

2011-01-01

Cachexia is a syndrome of wasting and anorexia that worsens the prognosis of many chronic diseases including cancer, chronic kidney disease, chronic heart disease and chronic obstructive pulmonary disease. Properties of the orexigenic hormone ghrelin—including appetite-stimulation, weight-gain production and increased cardiac output—make it a logical treatment for cachexia. While endogenous ghrelin levels are increased in the setting of cachexia, treatment with ghrelin and other GHSR-1a agonists in animal models of cachexia and in humans with cachexia have demonstrated consistent effects of increased appetite and improved weight gain. These positive effects occur in multiple underlying diseases associated with cachexia and appear to be sustained over treatment duration of up to 12 weeks. The mechanism of action in producing these effects is likely related to stimulation of central appetite centers such as the central melanocortin system and to increased growth hormone release, though ghrelin’s effects may also relate to decreased systemic inflammation and other direct and indirect actions. Questions regarding the long-term safety of ghrelin treatment are still unanswered, as is the important question of whether successful treatment of cachexia will improve the prognosis of the underlying disease itself. PMID:21354462

From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

PubMed Central

Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

2015-01-01

Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

PubMed

Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

2014-09-05

Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed Central

Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

2016-01-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

"I'm not abusing or anything": patient-physician communication about opioid treatment in chronic pain.

PubMed

Matthias, Marianne S; Krebs, Erin E; Collins, Linda A; Bergman, Alicia A; Coffing, Jessica; Bair, Matthew J

2013-11-01

To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients. This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation. Uncertainties about opioid treatment for chronic pain, particularly addiction and misuse, play an important role in communicating about pain treatment. Three patterns of responding to uncertainty emerged in conversations between patients and physicians: reassurance, avoiding opioids, and gathering additional information. Results are interpreted within the framework of Problematic Integration theory. Although it is well-established that opioid treatment for chronic pain poses numerous uncertainties, little is known about how patients and their physicians navigate these uncertainties. This study illuminates ways in which patients and physicians face uncertainty communicatively and collaboratively. Acknowledging and confronting the uncertainties inherent in chronic opioid treatment are critical communication skills for patients taking opioids and their physicians. Many of the communication behaviors documented in this study may serve as a model for training patients and physicians to communicate effectively about opioids. Published by Elsevier Ireland Ltd.

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

PubMed Central

Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

2014-01-01

Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia.

PubMed

Jabbour, Elias J; Hughes, Timothy P; Cortés, Jorge E; Kantarjian, Hagop M; Hochhaus, Andreas

2014-07-01

Despite vast improvements in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment.

Under one roof: identification, evaluation, and treatment of chronic hepatitis C in addiction care.

PubMed

Martin, Stephen A; Bosse, Jordon; Wilson, Amanda; Losikoff, Phyllis; Chiodo, Lisa

2018-04-25

For over a decade, the vast majority of new hepatitis C virus (HCV) infections have been among young people who inject drugs (PWID). Well-characterized gaps in chronic HCV diagnosis, evaluation, and treatment have resulted in fewer than 5% of PWID receiving HCV treatment. While interferon-based treatment may have intentionally been foregone during part of this time in anticipation of improved oral therapies, the overall pattern points to deficiencies and treatment exclusions in the health care system. Treatment for HCV with all-oral, highly effective direct-acting antiviral medication for 12 weeks or less is now the standard of care, putting renewed focus on effective delivery of care. We describe here both the need for and process of chronic HCV care under the roof of addiction medicine.

Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report

PubMed Central

Oneal, Brent J.; Patterson, David R.; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P.

2009-01-01

This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

PubMed

van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid hormone metabolism.

Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment.

PubMed

Kim, Helena K; Isaacs-Trepanier, Cameron; Elmi, Nika; Rapoport, Stanley I; Andreazza, Ana C

2016-05-01

Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse

PubMed Central

Malloul, Hanaa; Bennis, Mohammed; Bonzano, Sara; Gambarotta, Giovanna; Perroteau, Isabelle; De Marchis, Silvia; Ba-M'hamed, Saadia

2018-01-01

Thinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations. Yet, the sites and mechanisms of action of these compounds on the brain are far from being fully understood. Here, we investigated the consequences of paint thinner inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect were found following repeated exposure in chronic treatments lasting 12 weeks. Both subchronic (6 weeks) and chronic treatments impaired learning and memory functions, while no changes were observed after acute treatment. To investigate possible molecular/structural alterations underlying such behavioral changes, we focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation strongly affected adult neurogenesis in the dentate gyrus (DG), reducing progenitor cell proliferation after chronic treatments and impairing the survival of newborn neurons following both chronic and subchronic treatments. Furthermore, a down-regulation in the expression of BDNF and NMDA receptor subunits as well as a reduction in CREB expression/phosphorylation were found in the hippocampi of chronically treated mice. Our findings demonstrate for the first time significant structural and molecular changes in the adult hippocampus after prolonged paint thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly supporting its implication in the behavioral dysfunctions associated to inhalant abuse. PMID:29472835

Linaclotide: a novel therapy for chronic constipation and constipation-predominant irritable bowel syndrome.

PubMed

Lacy, Brian E; Levenick, John M; Crowell, Michael D

2012-10-01

Chronic constipation and irritable bowel syndrome (IBS) are functional gastrointestinal disorders that significantly affect patients' quality of life. Chronic constipation and IBS are prevalent-1 2% of the US population meet the diagnostic criteria for IBS, and 1 5% meet the criteria for chronic constipation- and these conditions negatively impact the healthcare system from an economic perspective. Despite attempts at dietary modification, exercise, or use of over-the-counter medications, many patients have persistent symptoms. Alternative treatment options are limited. This article describes linaclotide (Linzess, Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first-in-class medication for the treatment of chronic constipation and constipation-predominant IBS.