Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.

Aims: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials. Methods and results: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with ‘broad’ and ‘narrow’ preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18–96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33–1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75–1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF. Conclusion: We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted

The Relative Efficiency of Auditory (Social) Reinforcement vs. Food Reinforcement with the Squirrel Monkey (Saimiri Sciureus) in an Operant Situation

Research using non-deprivation and sensory or food reinforcement has received little attention to the present time. It is possible that, at least in the laboratory, sensory reinforcement under non- deprived conditions may be a much more economical and efficient reinforcer than food reinforcement under deprived conditions, which is traditionally used

Leadership Decisions: Situational Dimensions and Leaders\u27 Responses in Labor Intensive Industries

The problem of this study was to determine whether a relationship exists between situational leadership effectiveness of administrators in hospitals and principals in high schools in a selected geographical area. The data-gathering instruments were the Leader Effectiveness & Adaptability Description (LEAD-Self) and a one-page demographic sheet. The LEAD-Self provides a measurement of situational leadership style and leadership effectiveness based upon responses to 12 administrative decisions. Descriptive statistics were used to analyze the data gathered, with the Eta and Pearson\u27s product-moment being the correlation studies used. Six research questions were explored, dealing with the relationship between the effectiveness score and the following variables: age, number of employees reporting directly to the administrator, educational level of respondents, number of hours of monthly inservice or continuing education related to administration, years of administrative experience, and job position (hospital administrator or high school principal). The descriptive analysis of the study warranted the following conclusions: (1) The Pearson\u27s correlational studies revealed little or no relationship between effectiveness and respondents\u27 age, number of employees reporting directly, monthly inservice/continuing education, and years of administrative experience. (2) The Eta correlational studies revealed little to no relationship between effectiveness and respondents\u27 position or educational level

Consultation in the policy process: Douglasian cultural theory and the development of accounting regulation in the face of crisis

This article employs Douglasian cultural theory to explain how policy consultations intended to secure meaningful reform can, in fact, work to reinforce the status quo. The context for this is an examination of responses to three consultations established by the Financial Reporting Council (FRC), the body responsible for regulating accounting and auditing in the UK. The results reveal a lack of diversity of voices in the responses to three consultations, with the enclave and isolate voices being significantly under-represented despite the policy issues under debate being related to the financial crisis. Further, the initial pre-consultation proposals are largely unchanged post-consultation. We suggest that the regulator has not been captured; but instead is subject to what may be described as self-capture. Self-capture describes the instinctive reaction of a solidarity to act to uphold its pattern of social relations which results in the regulator's worldview inevitably (and unwittingly) being perpetuated