Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Variations in leopard cat (Prionailurus bengalensis) skull morphology and body size: sexual and geographic influences

The leopard cat, Prionailurus bengalensis (Kerr, 1792), is one of the most widespread Asian cats, occurring in continental eastern and southeastern Asia. Since 1929, several studies have focused on the morphology, ecology, and taxonomy of leopard cats. Nevertheless, hitherto there has been no agreement on basic aspects of leopard cat biology, such as the presence or absence of sexual dimorphism, morphological skull and body differences between the eleven recognized subspecies, and the biogeography of the different morphotypes. Twenty measurements on 25 adult leopard cat skulls from different Asian localities were analyzed through univariate and multivariate statistical approaches. Skull and external body measurements from studies over the last 77 years were assembled and organized in two categories: full data and summary data. Most of this database comprises small samples, which have never been statistically tested and compared with each other. Full data sets were tested with univariate and multivariate statistical analyses; summary data sets (i.e., means, SDs, and ranges) were analyzed through suitable univariate approaches. The independent analyses of the data from these works confirmed our original results and improved the overview of sexual dimorphism and geographical morphological variation among subspecies. Continental leopard cats have larger skulls and body dimensions. Skulls of Indochinese morphotypes have broader and higher features than those of continental morphotypes, while individuals from the Sunda Islands have skulls with comparatively narrow and low profiles. Cranial sexual dimorphism is present in different degrees among subspecies. Most display subtle sex-related variations in a few skull features. However, in some cases, sexual dimorphism in skull morphology is absent, such as in P. b. sumatranus and P. b. borneoensis. External body measurement comparisons also indicate the low degree of sexual dimorphism. Apart from the gonads, the longer hind foot of male leopard cats is the main feature of sexual dimorphism among P. b. bengalensis (and probably among P. b. horsfieldii too). External body measurements also indicated the absence of sexual dimorphism among individuals of P. b. borneoensis. Inter-subspecific skull comparisons provided a morphometric basis for differentiating some subspecies. Prionailurus b. horsfieldii and P. b. bengalensis were distinguished only by a subtle difference in PM4 size, indicating that overall skull morphology does not appear to support their separate taxonomical status, in spite of the marked differences reported in their coat patterns. Geological events affecting the Sunda Shelf connection between the Sunda Islands and the mainland during the Last Glacial Maximum seem to have influenced directly the morphological pattern shown by leopard cat subspecies nowadays

Patrones de vocalización de jóvenes y hembras adultas de Caiman yacare (Crocodilia: Alligatoridae) en el Pantanal de Brasil

The Paraguayan caiman (Caiman yacare) is the main Caimaninae species occurring in the Brazilian Pantanal Wetland. Despite the relative availability of works focused on biology and conservation of the Paraguayan caiman, almost nothing is known about its vocal structure and behavior. We recorded aggressive calls of adult caiman females guarding nests and, afterwards, the distress calls of the new born juvenile caimans in seasonally flooded areas of the Nhecolândia (Southern Pantanal). The results of both observations and sonographic analyses diverged from studies with other crocodilian species. Aggressive vocalization of adult females of the Paraguayan caiman was longer and more complex than the same vocalization of larger Alligatoridae species. Vocalizations of the young caimans presented interspecific differences with other crocodilian offsprings. Moreover, we found statistically significant intraspecific variation in the distress call structure among different pods, even separated by few kilometers. Differences in distress call structure were tested by Canonical Discriminant Analysis (CDA). We obtained the squared Mahalanobis distances between the acoustic multivariate spaces of each pod provided by the CDA and compared with the geographic distance between the bays of origin of each pod through Mantel Test. The geographic distance by itself did not explain the differences found in the structure of the vocalization of young caimans from different pods. The adult females of Paraguayan caiman positively responded to playbacks of calls from juvenile caimans from pods of other regions, as well as to rough imitations of distress call. Since the adult caimans showed protective responses to quite heterogeneous vocalizations of distress by juveniles, we hypothesized that the variation in the distress call pattern may be associated to a low specificity in sound recognition by adult caimans.Poco se conoce sobre la estructura vocal del Caiman yacare del Pantanal brasileño. Llamadas agresivas de hembras adultas que cuidaban de los nidos fueron registradas durante enero y febrero y llamadas de socorro de caimanes jóvenes, en abril de 1992. Hembras adultas de C. yacare presentaron una vocalización agresiva más larga y compleja que en otras especies más grandes de Alligatoridae. Las vocalizaciones de los jóvenes caimanes también presentaron diferencias interespecíficas con otros cocodrilos y variaciones intraespecíficas entre grupos separados por pocos kilómetros. Se utilizó la Prueba de Mantel para comparar las distancias de Mahalanobis entre la estructura de las vocalizaciones de los jóvenes de acuerdo con sus grupos y las distancias geográficas donde ellos estaban. La distancia geográfica en sí no explica las diferencias en las vocalizaciones de jóvenes de diferentes grupos. Hembras adultas de C. yacare han respondido a grabaciones de llamadas de caimanes de grupos de otras regiones, así como a imitaciones de llamada de socorro. Se postula que las variaciones en las llamadas de socorro pueden estar asociadas con una baja especificidad en el reconocimiento de sonido por caimanes adultos que han respondido de la misma forma protectora a las más heterogéneas expresiones de peligro de los jóvenes

Vocal patterns of adult females and juveniles Caiman yacare (Crocodilia: Alligatoridae) in Brazilian Pantanal wetland

The Paraguayan caiman (Caiman yacare) is the main Caimaninae species occurring in the Brazilian Pantanal Wetland. Despite the relative availability of works focused on biology and conservation of the Paraguayan caiman, almost nothing is known about its vocal structure and behavior. We recorded aggressive calls of adult caiman females guarding nests and, afterwards, the distress calls of the new born juvenile caimans in seasonally flooded areas of the Nhecolândia (Southern Pantanal). The results of both observations and sonographic analyses diverged from studies with other crocodilian species. Aggressive vocalization of adult females of the Paraguayan caiman was longer and more complex than the same vocalization of larger Alligatoridae species. Vocalizations of the young caimans presented interspecific differences with other crocodilian offsprings. Moreover, we found statistically significant intraspecific variation in the distress call structure among different pods, even separated by few kilometers. Differences in distress call structure were tested by Canonical Discriminant Analysis (CDA). We obtained the squared Mahalanobis distances between the acoustic multivariate spaces of each pod provided by the CDA and compared with the geographic distance between the bays of origin of each pod through Mantel Test. The geographic distance by itself did not explain the differences found in the structure of the vocalization of young caimans from different pods. The adult females of Paraguayan caiman positively responded to playbacks of calls from juvenile caimans from pods of other regions, as well as to rough imitations of distress call. Since the adult caimans showed protective responses to quite heterogeneous vocalizations of distress by juveniles, we hypothesized that the variation in the distress call pattern may be associated to a low specificity in sound recognition by adult caimans

Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach

<p>Abstract</p> <p>Background</p> <p>We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements.</p> <p>Methods</p> <p>Data from 189 female subjects (34.0±15.5 years, 30.5±7.1 kg/m²), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV_max), and the time taken to reach RBCV_max (TRBCV_max).</p> <p>Results</p> <p>A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV_max varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV_max, but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV_max). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity.</p> <p>Conclusions</p> <p>In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.</p

Drug prescription and delirium in older inpatients: Results from the nationwide multicenter Italian Delirium Day 2015-2016

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship