Writing PharmD Program-Level, Ability-Based Outcomes: Key Elements for Success

A set of PharmD program curricular outcomes form the foundation of a doctor of pharmacy (PharmD) curriculum and are critical to the development of both the structure/courses of the curriculum and the assessment plan for the program. A goal for developing these outcomes is to craft a set of clear, concise, assessable statements that accurately reflect competencies of the generalist entry-level pharmacist or graduate of the first-professional doctor of pharmacy degree. This article will provide a review of one specific type of outcome, ability-based outcomes, and present a case study of how one college revised their PharmD program-level outcomes. A discussion of key elements for the successful adoption of these outcomes is also presented.     

Information for clinical governance: analysis of routine hospital activity data in Wales

BACKGROUND: Variations in hospital admission rates have been extensively reported for many years, but this evidence has not had a wide impact on clinical practice. Understanding local reasons for high variation to improve quality of healthcare should be a focus of clinical governance. Our aim was to convert routine hospital activity data into information on a category of high-variation, discretionary, hospital admissions and provide a tool for analysis for clinical governors in Local Health Groups (LHG). METHODS: We undertook a cross-sectional analysis of hospital activity data for the 22 LHGs in Wales and 101 general practices in Gwent Health Authority. Hospital spells for 1998-1999 and 1999-2000 were classified into Healthcare Resource Groups (HRGs). Using the systematic component of variation we identified a category of high-variation admissions for which the only plausible explanation was medical discretion. Using scatter plots we compared the proportion of these discretionary admissions with the age-, sex- and deprivation-adjusted standardized admission ratio. (SAR) for each LHG and practice. RESULTS: We found a two-fold variation in SARs between LHGs and a three-fold variation between practices. Mean discretionary activity was 55 per cent (range 50-59 per cent) of total activity for LHGs and 56 per cent (51-62 per cent) for practices. Greatest variation was found for elective admissions. The relation between discretionary admissions and the SAR was identified for each LHG and practice as the starting point for further investigation. CONCLUSION: This method provides useful information to LHG clinical governors to contribute to the process of reducing medical practice variation, increasing equity, improving the quality of care and making more cost-effective use of resources.     

The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Mitoxantrone is the first drug approved for the treatment of secondary progressive multiple sclerosis (SPMS) in the United States. This assessment considers use of mitoxantrone in the treatment of MS. Mitoxantrone probably reduces the clinical attack rate and reduces attack-related MRI outcomes in patients with relapsing MS (Type B recommendation). Also, mitoxantrone may have a beneficial effect on disease progression in patients with MS whose clinical condition is worsening (Type B recommendation). The potential for serious toxicity of mitoxantrone, however, must be taken into account when considering this therapy in individual patients. Moreover, because the potential clinical benefits on disease progression appear to be only modest, the results of the single phase III trial should be replicated in another (and hopefully much larger) clinical study before this agent is widely recommended for the treatment of patients with MS.     

Lyme disease

Lyme disease is due to infection with a tick-borne spirochete, Borrelia burgdorferi. Risk for infection is confined to regions that contain the Ixodid tick vector. Characteristic skin, musculoskeletal, cardiac, ocular, and neurologic disorders are associated with the local, early dissemination and late stages of infection. Neurologic involvement can be seen at all stages, and involves both central and peripheral nervous system syndromes. The inability to easily culture B. burgdorferi and the lack of a reliable active infection assay have contributed to controversies in diagnosis and management. Because the vast majority of patients are seropositive, however, antibody testing is helpful to support the diagnosis of Lyme disease. With appropriate antibiotics, most patients do well. This infection provides an important model system to understand how interactions between an organism, vector, and host lead to disease. It also provides a model to study how infectious agents lead to neurologic disease.     

Randomized,comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial

BACKGROUND: Interferon beta (IFNbeta) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial. METHODS: This randomized, controlled, multicenter trial compared the efficacy and safety of IFNbeta-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFNbeta-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks. RESULTS: After 24 weeks, 74.9% (254/339) of patients receiving IFNbeta-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw. Patients receiving 44 micro g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw. Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage. Neutralizing antibodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw. CONCLUSIONS: IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.     

Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET

Receptor supersensitivity is an important concept for understanding neurotransmitter and receptor dynamics. Traditionally, detection of receptor supersensitivity has been performed using autoradiography or positron emission tomography (PET). We show that use of magnetic resonance imaging (MRI) not only enables one to detect dopaminergic supersensitivity, but that the hemodynamic time course reflective of this fact is different in different brain regions. In rats unilaterally lesioned with intranigral 6-hydroxydopamine, apomorphine injections lead to a large increase in hemodynamic response (cerebral blood volume, CBV) in the striato-thalamo-cortico circuit on the lesioned side but had little effect on the intact side. Amphetamine injections lead to increases in hemodynamic responses on the intact side and little on the lesioned side in the same animals. The time course for the increase in CBV after either amphetamine or apomorphine administration was longer in striatum and thalamus than in frontal cortex. (11)C-PET studies of ligands which bind to the dopamine transporter (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1, 5-naphthalnendisulfonate, WIN 35, 428 or CFT) and D2 receptors (raclopride) confirm that there is a loss of presynaptic dopamine terminals as well as upregulation of D2 receptors in striatum in these same animals. Pharmacologic MRI should become a sensitive tool to measure functional supersensitivity in humans, providing a complementary picture to that generated using PET studies of direct receptor binding.     

A changing paradigm of glioma biology

The past 30 years have witnessed a major paradigm shift in brain tumor research with the development of a wide variety of molecular     

The emerging role of glutamate in the pathophysiology and treatment of schizophrenia

OBJECTIVE: Research has implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia. This review evaluates evidence from preclinical and clinical studies that brain glutamatergic neurotransmission is altered in schizophrenia, may affect symptom expression, and is modulated by antipsychotic drugs. METHOD: A comprehensive review of scientific articles published over the last decade that address the role of glutamate in the pathophysiology of schizophrenia was carried out. RESULTS: Glutamatergic neurons are the major excitatory pathways linking the cortex, limbic system, and thalamus, regions that have been implicated in schizophrenia. Postmortem studies have revealed alterations in pre- and postsynaptic markers for glutamatergic neurons in several brain regions in schizophrenia. The N-methyl-D-aspartic acid (NMDA) subtype of glutamate receptor may be particularly important as blockade of this receptor by the dissociative anesthetics reproduces in normal subjects the symptomatic manifestations of schizophrenia, including negative symptoms and cognitive impairments, and increases dopamine release in the mesolimbic system. Agents that indirectly enhance NMDA receptor function via the glycine modulatory site reduce negative symptoms and variably improve cognitive functioning in schizophrenic subjects receiving typical antipsychotics. CONCLUSIONS: Dysfunction of glutamatergic neurotransmission may play an important role in the pathophysiology of schizophrenia, especially of the negative symptoms and cognitive impairments associated with the disorder, and is a promising target for drug development.