Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999-2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies-one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics

Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia

Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics

We conducted high-dimensional propensity score-adjusted cohort studies to examine whether thiazolidinedione use with a statin or fibrate was associated with an increased risk of severe hypoglycemia. We found that concomitant therapy with a thiazolidinedione+fibrate was associated with a generally delayed increased risk of severe hypoglycemia

Antidepressant-Warfarin Interaction and Associated Gastrointestinal Bleeding Risk in a Case-Control Study

Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.Medicaid claims data (1999-2005) were used to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years. In total, 430,455 warfarin users contributed 407,370 person-years of warfarin use. The incidence rate of hospitalization for GI bleeding among warfarin users was 4.48 per 100 person-years (95% CI, 4.42-4.55). Each gastrointestinal bleeding cases was matched to 50 controls based on index date and state. Warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of citalopram (OR = 1.73 [95% CI, 1.25-2.38]), fluoxetine (OR = 1.63 [95% CI, 1.11-2.38]), paroxetine (OR = 1.64 [95% CI, 1.27-2.12]), amitriptyline (OR = 1.47 [95% CI, 1.02-2.11]). Also mirtazapine, which is not believed to interact with warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]).Warfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk

Biologization of lifestyle of the inhabitant in the ideological tradition of American horror film

Актуальность. Переосмысление классических политических доминант актуализирует смыслы взаимодействия государства, общества и индивида. Отказ от прямого физического принуждения побуждает к поиску идеологических механизмов социального контроля. Голливуд становится медийным рупором биотической трансформации политики, а фильм ужасов превращается в наиболее эффективную модель визуализации этих технологий. Цель работы - проанализировать методологические стратегии биотизации обывательской повседневности в пространстве современной массовой культуры посредством идеологической экспансии традиции американских фильмов ужасов. Методы: комплекс компаративистских, семиотических и психоаналитических методов, анализирующих художественный опыт кинематографа и его мифологию. Результаты. Голливудские фильмы ужасов выступают апробированным средством сублимации, деформации и потребительского замещения ментального ядра любых конкурирующих социокультурных традиций. Американская визуальная хоррор-культура эффективно вытесняет потенциал агрессии внутри страны, превращаясь в прибыльную пропагандистскую технологию формирования и продвижения патомифа. Он воспроизводит преимущественно физиологические мотивы коммуникации индивида с окружающим миром, пропагандирует идейную доминанту биологически сильной особи как фундамент социокультурной коммуникации постчеловеческого типа. Американский фильм ужасов обнуляет экзистенциальный опыт человечества и находится в авангарде ревизии традиций не только европейской, но и мировой культуры. Выводы. Голливудская модель биовласти разрушает культурные традиции и исторический опыт, конструирует и продвигает антропологическую и социокультурную сингулярность человеческой особи, понимаемую как ее единичность в противостоянии отчужденному социуму, а периодически накапливающаяся «интоксикация» голливудским ужасом компенсируется иллюзией американской геополитической гегемонии.Relevance. Reinterpretation of classical political dominants actualizes the meanings of interaction between the state, society and individual. The rejection of direct physical coercion encourages the search for ideological mechanisms of social control. Hollywood is becoming a media mouthpiece for the biotic transformation of politics, and horror film is becoming the most effective model for visualizing these technologies. The aim. The article analyzes the strategies of biotization of everyday life in the space of modern mass culture through the ideological expansion of American horror films. Research. Domestic and foreign authors state the transformation of classical ideology into latent forms of control at the level of official and everyday practices. Methods. The article uses a complex of comparative, semiotic and psychoanalytic methods analyzing the artistic experience of cinema and its mythology. Results. Hollywood horror films are a proven means of sublimation, deformation and consumer substitution of the mental core of any competing socio-cultural traditions. American visual horror-culture effectively displaces the potential of aggression within the country, turning into a lucrative propaganda technology for formation and promotion of pathomif. It reproduces mainly physiological motives of communication of the individual with the world, promotes the ideological dominant of the biologically strong individual as the foundation of socio-cultural communication of the posthuman type. American horror film nullifies the existential experience of mankind; it is at the forefront of the revision of the traditions of not only European but also world culture. Findings. The Hollywood model of bio-power destroys cultural traditions and historical experience, constructs anthropological and socio-cultural singularity of the human individual, and periodically accumulating «intoxication» with Hollywood horror is compensated by the illusion of American geopolitical hegemony

Processing of disgusted faces is facilitated by odor primes: A functional MRI study

Facilitation of emotional face recognition is an established phenomenon for audiovisual crossmodal stimulation, but not for other sensory modalities. The present study used a crossmodal priming task to identify brain systems controlling olfactory–visual interactions during emotion processing. BOLD fMRI was acquired for 44 healthy subjects during an emotional face discrimination task preceded by an emotionally valenced odorant.Behavioral performance showed that recognition of disgusted faces was improved by the presentation of an olfactory stimulus irrespective of its emotional valence. No such facilitation was seen for other facial expressions. The neuroimaging data showed a selective default network responsivity to emotional faces which was modulated by odor condition. Among disgust faces, hypoactivations during trials preceded by odorants indicated the presence of priming effects. Consistent with studies investigating the brain systems associated with audiovisual emotional integration, activity modulations in clusters in fusiform gyrus, middle frontal and middle cingulate gyrus corresponded to the observed behavioral facilitation. Our study further shows modulation of signal in the anterior insula during trials combining negatively valenced odor and disgusted faces, suggesting a modality-specific mechanism for integration of the disgust response and olfaction. These results indicate the presence of a central network with modality-specific and -unspecific components modulating emotional face recognition