Costs of potentially inappropriate medication use in residential aged care facilities.

BACKGROUND: The potential harms of some medications may outweigh their potential benefits (inappropriate medication use). Despite recommendations to avoid the use of potentially inappropriate medications (PIMs) in older adults, the prevalence of PIM use is high in different settings including residential aged care. However, it remains unclear what the costs of these medications are in this setting. The main objective of this study was to determine the costs of PIMs in older adults living in residential care. A secondary objective was to examine if there was a difference in costs of PIMs in a home-like model of residential care compared to an Australian standard model of care. METHODS: Participants included 541 participants from the Investigation Services Provided in the Residential Environment for Dementia (INSPIRED) Study. The INSPIRED study is a cross-sectional study of 17 residential aged care facilities in Australia. 12 month medication costs were determined for the participants and PIMs were identified using the 2015 updated Beers Criteria for older adults. RESULTS: Of all of the medications dispensed in 1 year, 15.9% were PIMs and 81.4% of the participants had been exposed to a PIM. Log-linear models showed exposure to a PIM was associated with higher total medication costs (Adjusted ß = 0.307, 95% CI 0.235 to 0.379, p < 0.001). The mean proportion (±SD) of medication costs that were spent on PIMs in 1 year was 17.5% (±17.8) (AUD$410.89 ± 479.45 per participant exposed to a PIM). The largest PIM costs arose from proton-pump inhibitors (34.4%), antipsychotics (21.0%) and benzodiazepines (18.7%). The odds of incurring costs from PIMs were 52% lower for those residing in a home-like model of care compared to a standard model of care. CONCLUSIONS: The use of PIMs for older adults in residential care facilities is high and these medications represent a substantial cost which has the potential to be lowered. Further research should investigate whether medication reviews in this population could lead to potential cost savings and improvement in clinical outcomes. Adopting a home-like model of residential care may be associated with reduced prevalence and costs of PIMs.

Peripheral cholinesterase inhibition by occupational chlorpyrifos exposure in Australian termiticide applicators.

Occupational exposure to organophosphorus insecticides (OPs), such as chlorpyrifos, may be monitored by the measurement of the activity of peripheral cholinesterase (ChE) enzymes, including erythrocyte acetylcholinesterase (EAChE) and serum cholinesterase (SChE). Lymphocyte neuropathy target esterase (NTE) is thought to have potential as a predictor of organophosphate-induced delayed neuropathy (OPIDN). This paper describes work performed in 39 Australian pest control operators (PCOs) exposed to a termiticide containing chlorpyrifos, and 34 unexposed control subjects. EAChE activities in PCOs did not differ from those of unexposed control workers. Mean NTE activity was slightly higher in PCOs than in controls and mean SChE was 52% of control activity. These results indicate that exposure of Australian PCOs to termiticides containing chlorpyrifos may be monitored using SChE but not EAChE or NTE, and that workers in this industry have sufficiently high OP exposure to significantly depress SChE activity. SChE inhibition of 70-80% may be associated with symptoms. Although no current symptoms were reported to be associated with occupational OP exposure, these workers may be at increased risk of acute effects following inadvertent spills or self-contamination due to their background level of exposure to OPs. While it is preferable to compare ChE enzyme activities between pre- and post-exposure periods to evaluate OP-related effects in individuals, in some cases there is an absence of pre-exposure data. The results of this study suggest that a screening value for SChE of 550 nmol/min/ml in a single blood sample may be useful to identify potentially OP-exposed individuals in the Australian population. Australian control subjects were similar with respect to EAChE, but displayed activities of NTE and SChE approximately 50 and 23% lower than an unexposed UK reference group. While these comparisons are presently speculative, they suggest that there may be differences in SChE and NTE activities in control populations of the two countries. The routine treatment of Australian homes with termiticides containing OPs, or differences in the availability and use of domestic OP-containing insecticides may explain these population differences. Further work is required to examine whether these differences are real, and if so their likely cause.

5-Hydroxytryptamine-induced contraction of the marmoset aorta is mediated by a 5-HT1-like receptor.

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT2 antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta. 2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A2 agonist U44069 in order to amplify the responses; or (ii) exposed to N(omega)-nitro-L-arginine (100 micromol/L) plus LY 53857 (0.1 micromol/L; a 5-HT2 receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated. 3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT3 and 5-HT4 receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase. 4. The above effects fulfill the criteria for a 5-HT1-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT1-like receptor.

Physician-assessment and physician-enhancement programs in Canada.

In the mid-1980s, the licensing authorities in Quebec, Ontario and Manitoba have introduced programs to conduct in-depth assessments of the clinical skills and abilities of physicians with suspected deficiencies. These assessments are intended to supplement the provincial licensing authorities' existing peer review or patient-complaint mechanisms by confirming the physicians' overall level of competence and identifying specific clinical strengths and weaknesses. An "educational prescription", based on the results of the assessment, focuses on aspects of clinical practice in which the physicians need or wish to enhance their skills. In some situations, licensure decisions are based on the assessment information. This article describes the programs in Quebec, Ontario and Manitoba. Each program comprises a different process of personal assessment and individualized continuing medical education to help physicians improve their clinical competence, and each is built on sound principles of clinical competence assessment and educational planning.

Physician-assessment and physician-enhancement programs in Canada.

Since the mid-1980s, the licensing authorities in Quebec, Ontario and Manitoba have introduced programs to conduct in-depth assessments of the clinical skills and abilities of physicians with suspected deficiencies. These assessments are intended to supplement the provincial licensing authorities' existing peer review or patient-complaint mechanisms by confirming the physicians' overall level of competence and identifying specific clinical strengths and weaknesses. An "educational prescription," based on the results of the assessment, focuses on aspects of clinical practice in which the physicians need or wish to enhance their skills. In some situations, licensure decisions are based on the assessment information. This article describes the programs in Quebec, Ontario and Manitoba. Each program comprises a different process of personal assessment and individualized continuing medical education to help physicians improve their clinical competence, and each is built on sound principles of clinical-competence assessment and educational planning.

Interactions between 5-hydroxytryptamine, noradrenaline and the thromboxane-A2 mimetic U44069 in the marmoset isolated aorta.

1. The effects of 5-hydroxytryptamine (5-HT) in the absence and presence of noradrenaline (NA) or the thromboxane-A2 mimetic, U44069, were investigated in ring preparations of marmoset aorta. 2. 5-HT (0.001-10 mumol/L) produced little or no contractile response in preparations at basal tone. When the tone was elevated to 50% of maximum with NA the predominant response to 5-HT was relaxation. The 5-HT2 receptor antagonist LY53857 (0.1 mumol/L) unmasked a contractile response to low concentrations of 5-HT (0.01-1.0 mumol/L) and reduced relaxation to high concentrations of 5-HT (1.0-10 mumol/L) in vessels precontracted with NA. 3. In U44069-contracted vessels, 5-HT was contractile in the range 0.01-1 mumol/L and relaxant in concentrations of 6.0-10.0 mumol/L. Ketanserin (1.0 mumol/L) had no effect on the contraction or relaxation to 5-HT. 4. The relaxant response to 5-HT was not significantly diminished in endothelium-impaired arteries. 5. In conclusion, 5-HT exerts complex inhibitory and excitatory actions on the marmoset aorta. The inhibitory actions are not endothelium-dependent and the excitatory actions do not appear to involve the 5-HT2 receptor.

Identification of a nonendothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats.

Aortic ring preparations from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with N omega-nitro-L-arginine (NOLA, 10(-4) M). This produced a sustained contraction in preparations from SHR but not WKY rats. A similar contraction in aortic ring preparations from the SHR was produced with methylene blue (10(-5) M) and NG-monomethyl-L-arginine (10(-5) M). The NOLA-induced contraction was reversed with indomethacin (8 x 10(-6) M), ridogrel (10(-5) M) and SQ 29548 (10(-6) M) thus confirming the involvement of thromboxane A2/prostaglandin H2 processes. Subsequent experiments demonstrated that the thromboxane-like contraction was not dependent upon the presence of endothelial cells and occurred in preparations from young, prehypertensive (5 week) and older (17 week) SHRs. The thromboxane-like contraction was markedly suppressed with chronic captopril treatment and reinstated 4 weeks after withdrawal from captopril. The addition of saralasin (10(-6) M) or captopril (10(-6) M) to aortic ring preparations did not suppress the thromboxane-like contractions. The foregoing findings support the presence of a nonendothelial cell thromboxane-like constrictor agent in the aorta of the SHR that is revealed after impairment of nitric oxide production. The activity of the thromboxane-like constrictor process is not tightly linked to prevailing blood pressure, but is reduced with chronic in vivo inhibition of the angiotensin-converting enzyme.

Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases.

Little is known about the signaling pathways by which motoneurons induce synapses on muscle fibers, and no receptors for synapse-inducing signals have yet been identified. Because several other inductive events in development are mediated by receptor tyrosine kinases (RTKs), and because phosphotyrosine staining within muscle fibers is concentrated at synaptic sites, one possibility is that synapse-inducing signals are transduced by a RTK within the muscle fiber. We have used PCR to search for tyrosine kinases within the electric organ of the electric ray Torpedo californica, since this tissue is homologous to muscle but is much more densely innervated and is therefore a rich source of synaptic molecules. We have isolated a RTK that is specifically expressed in electric organ and skeletal muscle. The kinase domain of this receptor is related to the trk family of neurotrophin receptors, but unlike any previously described receptor, the extracellular region of this Torpedo RTK contains a kringle domain close to the transmembrane domain.

The influence of chronic captopril treatment and its withdrawal on endothelium-dependent relaxation.

The current experiments were designed to explore the relationship between the renin angiotensin system (RAS) and prostanoid formation in aortic ring preparations from spontaneously hypertensive rats (SHR). A further aim was to examine the mechanisms responsible for the reversal of the impaired acetylcholine (ACh) mediated relaxation induced by chronic administration of the angiotensin converting enzyme inhibitor captopril and the relationship of the ACh response to blood pressure. Rats were administered captopril (100 mg/kg/day) and their blood pressures monitored from 5 to 17 weeks of age. ACh-mediated relaxation was determined in aortic ring preparations from untreated and treated rats, and drug withdrawn rats. The influence of indomethacin, saralasin, SQ29548 and captopril on ACh-mediated responses was determined. It was found that chronic captopril treatment produced a marked suppression of the development of hypertension in the SHR. After the withdrawal of the drug the blood pressure remained significantly lower than in untreated animals for 4 weeks. ACh relaxation was impaired in SHR ring segments; this was reversed with captopril treatment and returned to the impaired state upon withdrawal of the drug. In vitro inhibition of the RAS did not significantly influence ACh relaxation. In contrast, impairment of the prostanoid system in vitro reversed the impaired relaxation. The results suggest that the influence of captopril on enhancing ACh relaxation in the SHR does not involve an acute interaction of local angiotensin II synthesis with prostanoid mechanisms. Importantly, the results highlight a dissociation between the impaired ACh relaxation and elevated blood pressure in the SHR.

Dystrophin is a component of the subsynaptic membrane.

A subsynaptic protein of Mr approximately 300 kD is a major component of Torpedo electric organ postsynaptic membranes and copurifies with the AChR and the 43-kD subsynaptic protein. mAbs against this protein react with neuromuscular synapses in higher vertebrates, but not at synapses in dystrophic muscle. The Torpedo 300-kD protein comigrates in SDS-PAGE with murine dystrophin and reacts with antibodies against murine dystrophin. The sequence of a partial cDNA isolated by screening an expression library with mAbs against the Torpedo 300-kD protein shows striking homology to mammalian dystrophin, and in particular to the b isoform of dystrophin. These results indicate that dystrophin is a component of the postsynaptic membrane at neuromuscular synapses and raise the possibility that loss of dystrophin from synapses in dystrophic muscle may have consequences that contribute to muscular dystrophy.

Multiple dystrophin isoforms are associated with the postsynaptic membrane of Torpedo electric organ.

We have shown previously that dystrophin is a component of postsynaptic membranes in Torpedo electric organ and is localized at mammalian neuromuscular synapses. In skeletal muscle, dystrophin is also detectable at the non-synaptic membrane of the myofiber, whereas in the electric organ, dystrophin is strictly localized to the postsynaptic membrane, and is not detectable in non-synaptic membranes. Multiple isoforms of dystrophin are present in skeletal muscle, and different isoforms could potentially be targetted to synaptic and non-synaptic membranes. We sought to determine whether the electric organ contains a single, or multiple isoforms of dystrophin, and we show here that the electric organ contains both a and b isoforms of dystrophin. Because dystrophin is found only at the postsynaptic membrane of the electric organ, we conclude that the two isoforms coexist in the postsynaptic membrane.

Wiener filtering improves quantification of regional myocardial perfusion with thallium-201 SPECT.

Quantitation of myocardial perfusion with thallium-201 (201Tl) SPECT is limited by finite resolution and image noise. This study examined whether Wiener filtering could improve quantitation of the severity of myocardial perfusion deficits. In 19 anesthetized dogs, adjustable stenoses were placed on the left anterior descending (LAD, n = 12) or circumflex (LCx, n = 7) arteries. Thallium-201 SPECT images were acquired during maximal coronary vasodilation with dipyridamole, and simultaneous measurements of myocardial blood flow were made with microspheres. The relationship between SPECT and microsphere flow deficits in the LAD region was significantly better (p less than 0.05) with Wiener filtering (Y = 0.90X + 0.03, r = 0.78) than with conventional Hanning filtering (Y = 0.66X + 0.34, r = 0.61). Similarly, in the LCx region the relationship between SPECT and microsphere perfusion deficits was better (p less than 0.01) with the Wiener filter (Y = 0.91X + 0.07, r = 0.66) than with the Hanning filter (Y = 0.36X + 0.50, r = 0.40). Wiener filtering improves quantitation of the severity of regional myocardial perfusion deficits, allowing better assessment of the functional significance of coronary artery stenoses.