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Cariprazine is a potent D3/D2 partial agonist with preferential binding to D3 receptors.
To evaluate the efficacy and safety of cariprazine versus placebo in acute exacerbation of schizophrenia.
A multinational, multicenter, double-blind, randomized, placebo- and active-controlled, fixed-dose trial in patients aged 18–60 years with DSM-IV-TR-defined schizophrenia, current psychotic episode < 2 weeks, and PANSS total score between 80 and 120. After 1-week washout, patients received 6-weeks treatment (cariprazine 1.5, 3.0, or 4.5 mg/d, risperidone 4.0 mg/d, or placebo) and 2-week safety follow-up. Risperidone was used to assess assay sensitivity. Primary and secondary efficacy: baseline to Week 6 change (LOCF) in PANSS total and CGI-S scores, respectively. Safety: adverse events (AEs), vital signs, laboratory measures, extrapyramidal symptom (EPS) scales.
Of 732 randomized patients, 64% completed the study. Mean baseline PANSS (98) and CGI-S scores (4.8) were similar across groups. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (placebo-adjusted improvements: −7.5, −8.9, −10.4, respectively; P < .001; LOCF) and risperidone (−15.0, P < .001, LOCF); significant improvement on CGI-S was demonstrated for all active treatments (P < .05). The most common cariprazine AEs were insomnia, EPS, akathisia, sedation, nausea, dizziness, and constipation. AE discontinuation rates were 15% for placebo, 10%, 5% and 8% for cariprazine 1.5, 3.0, and 4.5 mg/d, respectively, and 9% for risperidone 4.0 mg/d.
Cariprazine significantly improved PANSS and CGI-S scores versus placebo in acute exacerbation of schizophrenia and was generally well tolerated.
To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate
Prospective cohort study
US multicenter, quality-improvement, BSI prevention network
PHO centers across the United States who agreed to follow a standardized central-line–maintenance care bundle and track all BSI events and central-line days every month.
Infections were categorized as CLABSI (stratified by mucosal barrier injury–related, laboratory-confirmed BSI [MBI-LCBI] versus non–MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked.
Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates.
Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public.
Based on seven measured sections from Svalbard, the marine strata of the Permian Kapp Starostin Formation are arranged into seven transgressive–regressive sequences (TR1–TR7) of c. 4–5 Ma average duration, each bound by a maximum regressive surface. Facies, including heterozoan-dominated limestones, spiculitic cherts, sandstones, siltstones and shales, record deposition within inner, middle and outer shelf areas. The lowermost sequence, TR1, comprises most of the basal Vøringen Member, which records a transgression across the Gipshuken Formation following a hiatus of unknown duration. Temperate to cold, storm-dominated facies established in inner to middle shelf areas between the latest Artinskian and Kungurian. Prolonged deepening during sequences TR2 and TR3 was succeeded by a long-term shallowing-upward trend that lasted until the latest Permian (TR4–TR7). A major depocentre existed in central and western Spitsbergen while to the north, Dickson Land remained a shallow platform, leading to a shallow homoclinal ramp in NE Spitsbergen and Nordaustlandet. The Middle Permian extinction (late Capitanian) is recorded near the base of TR6 in deeper parts of the basin only; elsewhere this sequence is not recorded. Likewise the youngest sequence, TR7, extending to the upper formational contact of latest Permian age, is found only in the basin depocentre. Comparison with age-equivalent strata in the Sverdrup Basin of Canada reveals a remarkably similar depositional history, with, for example, two (third-order) sea-level cycles recorded in the Late Permian of both regions, in keeping with the global record. Sequence stratigraphy may therefore be a powerful correlative tool for onshore and offshore Permian deposits across NW Pangaea.
This study assessed attachment representation and attachment-related autonomic regulation in a sample of 38 maltreating and 35 nonmaltreating mothers. Mothers’ state of mind regarding attachment was measured using the Adult Attachment Interview. They further watched an attachment-based comfort paradigm, during which we measured skin conductance and vagal tone. More maltreating mothers (42%) than nonmaltreating mothers (17%) had an unresolved/disoriented attachment classification. Attachment representation was related to physiology during the comfort paradigm: an unresolved state of mind and a nonautonomous classification were associated with a decrease in skin conductance during the comfort paradigm, specifically during the responsive caregiver scenario. However, physiology did not differ between maltreating and nonmaltreating mothers. The decrease in skin conductance of unresolved mothers during the comfort paradigm might be indicative of a deactivating response, which is congruent with the dissociative nature of the unresolved state of mind. The results point to the potential utility of interventions focused on attachment representations for maltreating mothers.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
Using a validated air sampling method we found Acinetobacter baumannii in the air surrounding only 1 of 12 patients known to be colonized or infected with A. baumannii. Patients’ closed-circuit ventilator status, frequent air exchanges in patient rooms, and short sampling time may have contributed to this low burden.
This paper contributes to research on defined contribution (DC) retirement plans by examining how financial knowledge and demographic factors influenced Chile's pension holders' choice between a default life-cycle retirement plan and active management. About one third of Chileans held default funds in 2009; younger people, men, people with lower incomes, and people with low financial knowledge were more likely to choose the default. For active investors, we examined what variables influenced their choice. Nearly three quarters of active investors chose more risky funds that the defaults for their age group. However, risk taking tended to decrease with age and to increase with income, financial knowledge and risk tolerance.
Polarimetry of the far infrared emission from magnetically-aligned interstellar grains is one of the best ways of studying the magnetic field at the Galactic center. We describe the HAWC+ instrument, under development for flight on SOFIA starting in 2015, which will provide a major advance in capability for these critically important measurements.
Across 36 US pediatric oncology centers, 576 central line-associated bloodstream infections (CLABSIs) were reported over a 21-month period. Most infections occurred in those with leukemia and/or profound neutropenia. The contribution of viridans streptococci infections was striking. Study findings depict the contemporary epidemiology of CLABSIs in hospitalized pediatric cancer patients.
Data on the dynamics of malaria incidence, admissions and mortality and their best possible description are very important to better forecast and assess the implementation of programmes to register, monitor (e.g. by remote sensing) and control the disease, especially in endemic zones. Semi-annual and seasonal cycles in malaria rates have been observed in various countries and close similarity with cycles in the natural environment (temperature, heliogeophysical activity, etc.), host immunity and/or virulence of the parasite suggested. This study aimed at confirming previous results on malaria cyclicity by exploring whether trans-year and/or multiannual cycles might exist. The exploration of underlying chronomes (time structures) was done with raw data (without smoothing) by linear and nonlinear parametric regression models, autocorrelation, spectral (Fourier) and periodogram regression analysis. The strongest cyclical patterns of detrended malaria admissions were (i) annual period of 1·0 year (12 months or seasonality); (ii) quasi-biennial cycle of about 2·25 years; and (iii) infrannual, circadecennial cycle of about 10·3 years. The seasonal maximum occurred in May with the minimum in September. Notably, these cycles corresponded to similar cyclic components of heliogeophysical activity such as sunspot seasonality and solar activity cyclicities and well-known climate/weather oscillations. Further analyses are thus warranted to investigate such similarities. In conclusion, multicomponent cyclical dynamics of cerebral malaria admissions in Papua New Guinea were observed thus allowing more specific analyses and modelling as well as correlations with environmental factors of similar cyclicity to be explored. Such further results might also contribute to and provide more precise estimates for the forecasting and prevention, as well as the better understanding, of the dynamics and aetiology of this vector-borne disease.