Perceptions of Justice in Clinical Learning Environments: Development and Validation of an Organizational Justice Measure for Medical Trainees.

PURPOSE: This study aimed to develop an instrument to measure medical trainees' perceptions of justice in clinical learning environments. METHOD: Between 2019 and 2023, the authors conducted a multiyear, multi-institutional, multiphase study to develop a 16-item justice measure with 4 dimensions: interpersonal, informational, procedural, and distributive. The authors gathered validity evidence based on test content, internal structure, and relationships with other variables across 3 phases. Phase 1 involved drafting items and gathering evidence that items measured intended dimensions. Phase 2 involved analyzing relevance of items for target groups, examining interitem correlations and factor loadings in a preliminary analysis, and obtaining reliability estimates. Phase 3 involved a confirmatory factor analysis and collecting convergent and discriminant validity evidence. RESULTS: In phase 1, 63 of 91 draft items were retained following a content validation exercise gauging how well items measured targeted dimensions (mean [SD] item ratings within dimensions, 4.16 [0.36] to 4.39 [0.34]) on a 5-point Likert scale (with 1 indicating not at all well and 5 indicating extremely well). In phase 2, 30 items were removed due to low factor loadings (i.e., < 0.40), and 4 items per dimension were selected (factor loadings, 0.42-0.89). In phase 3, a confirmatory factor analysis supported the 4-dimension model (χ2 = 610.14, P < .001; comparative fit index = 0.90, Tucker-Lewis Index = 0.87, root mean squared error of approximation = 0.11, standardized root mean squared residual = 0.06), with convergent and discriminant validity evidence showing hypothesized positive correlations with a justice measure (r = 0.93, P < .001), trait positive affect (r = 0.46, P < .001), and emotional stability (r = 0.33, P < .001) and negative correlations with trait negative affect (r = -0.39, P < .001). CONCLUSIONS: Results indicate the measure's potential utility in understanding justice perceptions and designing targeted interventions.

Is long-term treatment of Alzheimer's disease with cholinesterase inhibitor therapy justified?

The cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine are the current mainstays in the drug treatment of Alzheimer's disease (AD). There is convincing evidence that these agents provide at least modest cognitive, behavioural and functional benefit for 6-12 months at all stages of the disease. Longer term benefits cannot be directly examined by placebo-controlled trials. Nevertheless, the results of virtually all open-label extensions of the pivotal trials, studies of patients with AD at different levels of severity and clinical trials using other designs favour treatment over no treatment for periods of up to 5 years. There are plausible biological reasons why ChEIs might be expected to work over a prolonged period of time although, to date, studies using various markers to chart the effects of medication on long-term disease progression have yielded mixed results. The most contentious issue regarding long-term treatment is economic, but the majority of available economic analyses suggest net savings over the long term if patients with AD receive persistent treatment with ChEIs.

Neurochemical organization of chimpanzee inferior pulvinar complex.

The pulvinar of primates, which connects with all visual areas, has been implicated in visual attention and in control of eye movements. Recently, five separate neurochemical subdivisions of a region termed the inferior pulvinar complex have been identified in monkeys (Gray et al. [1999] J Comp Neurol 409:452-468; Gutierrez et al. [1995] J Comp Neurol 363:545-562), and comparable subdivisions have been mapped in humans (Cola et al. [1999] NeuroReport 10:3733-3738). In the present study, we investigated the inferior pulvinar of the chimpanzee (Pan troglodytes), the closest evolutionary relative of humans, using cytochrome oxidase (CO) and acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for calbindin. Each staining method demarcated five histochemical zones corresponding, from medial to lateral, to the posterior (PI(P)), medial (PI(M)), central PI(C)), lateral (PI(L)), and the lateral-shell (PI(L-S)) divisions in monkeys. The PI(P) division stained darkly for calbindin and lightly for CO and AChE. The PI(M) division was characterized by less neuropil staining for calbindin, and by distinct, intensely stained patches of CO and AChE. PI(C) appeared lighter than adjacent divisions with CO and AChE histochemistry and was moderately stained with calbindin. PI(L) was moderately to darkly stained with each method and was adjoined by a lighter staining shell, PI(L-S). Thus, in the aspects of organization we examined, the inferior pulvinar of chimpanzees closely resembles that of humans and monkeys. This investigation provides a foundation for more detailed studies of the thalamic relationships of extrastriate cortex in apes and humans.

Donepezil: a review.

Donepezil is a selective acetylcholinesterase inhibitor that is widely prescribed for Alzheimer's disease (AD). It has been shown to be of benefit in mild, moderate and severe stages of AD, vascular dementia and dementia associated with Parkinson's disease. Donepezil is absorbed slowly, but completely, from the gut, reaching peak plasma levels in 3-4 h and, with daily dosing, steady-state concentration in 15-21 days. Within a relatively narrow range, there is a linear relationship between dose and pharmacodynamic effects, measured as red blood cell acetylcholinesterase inhibition and clinical efficacy. Donepezil is principally excreted unchanged in the urine, but there is also hepatic metabolism; some of its metabolites may be active. Despite being 96% bound to plasma proteins, it has few interactions with other drugs, and the 5-mg dose can be given safely to patients with mild-to-moderate hepatic and renal -disease. Side effects, which are mainly a consequence of its cholinomimetic mechanism of action, are usually mild and transient. Although donepezil was originally developed to inhibit the breakdown of the neurotransmitter acetylcholine as symptomatic therapy for AD, recent studies raise the possibility of other effects this drug has on the pathogenesis of AD.

Architectonics and cortical connections of the upper bank of the superior temporal sulcus in the rhesus monkey: an analysis in the tangential plane.

Area TPO in the upper bank of the superior temporal sulcus (STS) of macaque monkeys is thought to correspond to the superior temporal polysensory (STP) cortex, but has been shown to have neurochemical/connectional subdivisions. To examine directly the relationship between chemoarchitecture and cortical connections of area TPO, the upper bank of the STS was sectioned tangential to the cortical surface. Three subdivisions of area TPO (TPOr, TPOi, and TPOc) were examined with cytochrome oxidase (CO) histochemistry and neurofilament protein (NF) immunoreactivity and architectonic patterns were compared with connections on the same or adjacent sections. Area TPOc, which may partly overlap with the location of the medial superior temporal area MST, exhibited regular patchy staining for CO in layers III/IV and a complementary pattern in the NF stain. Area TPOr, but not TPOi, also had a patchy pattern of complementary staining in CO and neurofilament similar to TPOc, although not as distinct. Tracer injections within cortex including the frontal eye fields (areas 46 and 8) labeled areas TPOc, TPOi, and TPOr. The caudal inferior parietal lobule (IPL) projected to all three areas. The projections from prearcuate and posterior parietal cortices showed both overlap and nonoverlap with each other within TPOc, TPOi, and TPOr. Projections were to all neurochemical components within the subdivisions of TPO. The findings support the parcellation of area TPO into three subdivisions and extend findings of chemoarchitectonic modules within high-order association cortices.

Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease. DESIGN: Multicenter, randomized, double-blind, 24-week, placebo-controlled study that enrolled patients with early-stage Alzheimer disease. Patients were randomized in an approximately 2:1 ratio to donepezil, 5 mg/d, for the first 6 weeks, with a forced escalation to 10 mg/d thereafter (n = 96), or placebo (n = 57). The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale. Secondary efficacy measures included the Mini-Mental State Examination, the Computerized Memory Battery Test, the Clinical Dementia Rating Scale-Sum of the Boxes, the Patient Global Assessment Scale, and the Apathy Scale. RESULTS: Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point (last observation carried forward); treatment differences were 1.9 (P = .03), 2.3 (P = .008), and 2.3 (P = .001) points, respectively. Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6, 12, and 24 and at the end point (last observation carried forward); treatment differences were 1.4 (P = .02), 1.2 (P = .04), 1.4 (P = .03), and 1.8 (P = .002) points, respectively. Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales: facial recognition (P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population), first and last name total acquisition (P = .02), and name-face association delayed recall (P = .04). Donepezil was safe and well tolerated in this population; serious adverse events occurred in similar numbers of donepezil- and placebo-treated patients. CONCLUSION: These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease, supporting the initiation of therapy early in the disease course to improve daily cognitive functioning.

Cognitive components of deficit awareness in Alzheimer's disease.

Awareness of deficit was examined in 24 patients with Alzheimer's disease (AD) and their spouses (for a total of 48 participants) using performance prediction-postdiction and questionnaire discrepancy (QD) paradigms. Participants estimated their own memory performances as well the performances of spouses and of a fictional, memory-disordered patient observed on videotape. Patients overpredicted self-performances, but the extent of overestimation decreased for postdictions. Patients and caregivers accurately estimated caregiver performances but overestimated performances of the fictional patient. QD data revealed that patients underestimated their difficulties performing daily functioning tasks as compared with caregiver reports. Awareness of deficit is a complex ability, involving dissociable cognitive processes. AD patients may display intact immediate awareness of memory dysfunction but fail to incorporate incidents of memory failure into generalized self-belief systems.

Galantamine-ER for the treatment of mild-to-moderate Alzheimer's disease.

An extended release form of the cholinesterase inhibitor (ChEI) drug galantamine (galantamine-ER) was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer's disease (AD). Except for predicted differences in (C(max)) and t(max), comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR), are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24) showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs.

Donepezil: an update.

Donepezil hydrochloride is the most widely prescribed drug for Alzheimer's disease (AD). The main mechanism of action through which it influences cognition and function is presumed to be the inhibition of acetylcholinesterase enzyme in the brain; however, donepezil may also impact the pathophysiology of AD at several other points. Officially approved for mild-to-moderate and severe AD, donepezil has also been shown to be effective in early-stage AD, vascular dementia, Parkinson's disease dementia/Lewy body disease and cognitive symptoms associated with multiple sclerosis. In addition, one study suggested that donepezil may delay the onset of AD in subjects with mild cognitive impairment, a prodrome to AD. The pharmacokinetics, pharmacodynamics, safety/tolerability profile and drug interaction properties of donepezil make it an easy and safe agent to use. However, in general, the efficacy of donepezil is limited, and ongoing studies are investigating other agents that may ultimately overtake its present position as the mainstay of anti-AD therapy.