Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

Asymmetric space closure

In a vertically slotted 0.022 X 0.028 inch edgewise system, the use of a two-dimensional ribbon arch--0.022 X 0.016 inch from lateral incisor to lateral incisor and 0.016 X 0.022 inch from the canine to the molars--plus an uprighting spring on the canine maintained incisor position while unilaterally protracting a molar-premolar unit by means of sliding mechanics. Five degrees of labial crown torque was placed in the incisor portion of the wire and the uprighting spring exerted a force of 200 to 250 g. The intra-arch force applied to protract the molar--premolar unit was 300 to 350 g.     

Superficial bladder cancer: intravesical chemotherapy and tumour progression to muscle invasion or metastases

Of 299 patients who presented with superficial bladder cancer (Ta, T1), 60 were treated by intravesical chemotherapy (Epodyl, methotrexate or mitomycin C). The rate of tumour progression to muscle invasion or metastases was identical for each intravesical regime. There was no evidence that mitomycin C promoted tumour progression. Carcinoma in situ in non-tumour-bearing urothelium was the most significant predictive factor for progression to muscle invasion or metastases.     

ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

Digital imaging with a photostimulable phosphor in the chest of newborns

To evaluate use of a digital photostimulable phosphor imaging system in the neonatal nursery, 150 newborns were divided into three groups of 50. In the first two groups, screen-film and computed radiographs of the chest were obtained at the same radiation exposure; in the third group, computed radiographs were obtained with a 50% dose reduction (half-exposure computed radiographs). All images were blindly evaluated by three readers who scored the quality of visualization of the mediastinum, lung, bone, soft tissues, and endotracheal and nasogastric tubes, and also image density. No statistical differences in visualization of tubes existed among the three groups. Visualization of the mediastinum, lung, bones, and soft tissues was statistically significantly better on computed radiographs than on half-exposure computed radiographs; visualization of the lungs, bones, and soft tissues was statistically significantly better on screen-film radiographs than half-exposure computed radiographs. Image density was statistically better on computed and half-exposure computed radiographs than on screen-film radiographs.     

Evidence for a distinct nigropallidal dopaminergic projection in the squirrel monkey

Injections of the retrograde fluorescent tracer fast blue in the striatum (STR) and nuclear yellow in the internal segment of the globus pallidus (GPi) in the squirrel monkey (Saimiri sciureus) revealed a nigropallidal projection whose cellular origin was largely distinct from that of the nigrostriatal pathway. Neurons containing the tracer injected in GPi were scattered throughout the substantia nigra-ventral tegmental area complex where they formed approximately 20-25% of the total number of retrogradely labeled cells. Only about 5-10% of all positive neurons were double-labeled after STR-GPi injections. In experiments combining the use of the fluorescent tracer propidium iodide with immunofluorescence, the majority of neurons projecting to GPi displayed tyrosine hydroxylase immunoreactivity. Hence, in addition to their important role at striatal level, midbrain dopaminergic neurons may influence directly the output neurons of the basal ganglia at pallidal level in primates.     

Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord

Acute experimental allergic encephalomyelitis (EAE) in the Lewis rat is a cell-mediated autoimmune disease of central nervous system myelin. The lesion has been characterized by breakdown of the blood-brain barrier, edema, and periventricular infiltration of macrophages and lymphocytes. At the early stage of the disease, the astrocytes show a marked increase in immunostaining for glial fibrillary acidic protein (GFAP). A corresponding increase in GFAP content, however, cannot be demonstrated. Electron microscopic examination of the early lesion shows a typical reactive astrocytic response expressed by an enlarged watery cytoplasm, particularly at the level of the processes surrounding neurons and blood vessels and in the neuropil itself. The astroglial processes contain numerous glycogen particles (aggregates and single particles). Glial filaments are also conspicuous and are arranged in small bundles or loose thin filaments adjacent to the bundles. The glial filaments that normally appear as tight bundles have expanded and appear less dense. We suggest that the increase in GFAP immunostaining of the astrocytes in the early lesion is due in part to edema, which causes dissociation of the filaments and thereby exposes more antigenic sites to the antibodies.