Measuring anticholinergic drug exposure in older community-dwelling Australian men: a comparison of four different measures

Aims

Anticholinergic drug exposure is associated with adverse outcomes in older people. While a number of tools have been developed to measure anticholinergic drug exposure, there is limited information about the agreement and overlap between the various scales. The aim of this study was to investigate the agreement and overlap between different measures of anticholinergic drug exposure in a cohort of community-dwelling older men.

Methods

A cross-sectional study was used to compare anticholinergic drug exposure calculated using the Anticholinergic Risk Scale (ARS), the Anticholinergic Drug Scale (ADS), the Anticholinergic Cognitive Burden (ACB) and the Drug Burden Index anticholinergic subscale (DBI-ACH) in a cohort of community-dwelling men aged 70 years and older (n = 1696). Statistical agreement, expressed as Cohen''s kappa (κ), between these measurements was calculated.

Results

Differences were found between the tools regarding the classification of anticholinergic drug exposure for individual participants. Thirteen percent of the population used a drug listed as anticholinergic on the ARS, 39% used a drug listed on the ADS and the ACB, and 18% of the population used one or more anticholinergic drugs listed on the DBI-ACH. While agreement was good between the ACB and ADS (κ = 0.628, 95% CI 0.593, 0.664), little agreement was found between remaining tools (κ = 0.091–0.264).

Conclusions

With the exception of the ACB and ADS, there was poor agreement regarding anticholinergic drug exposure among the four tools compared in this study. Great care should be taken when interpreting anticholinergic drug exposure using existing scales due to the wide variability between the different scales.     

Pulse pressure amplification in relation to body fatness

AIMS

Arterial pressure transfer to the periphery is accompanied by pulse pressure amplification (PPA). Pulse pressure is influence by body fat. The purpose of the present study was to evaluate any possible inter-relation between body fatness and PPA in healthy subjects.

METHODS

Haemodynamic and wave reflection indices were estimated by pulse wave analysis. Body fat was measured by bio-impedance.

RESULTS

A total of 367 healthy volunteers (136 men and 231 women) was studied. Pulse pressure amplification correlated significantly with percentage of body fat (r = −0.53, P < 0.0001), age (r = −0.62, P < 0.0001), height (r = 0.43, P < 0.0001), heart rate (r = 0.28, P < 0.0001) and mean blood pressure (r = −0.29, P < 0.0001). The association of PPA with body fat was also significant in a multiple linear regression model. Age was an independent predictor of PPA and analysis of study subjects subdivided into two groups, those <50 years and those >50 years showed that body fatness correlated inversely and significantly with PPA in individuals both younger and older than 50 years (r = −0.44, P < 0.0001, r = −0.37, P < 0.0001 respectively). Augmentation pressure was also associated significantly with percentage of body fat in both subgroups (r = 0.48, P < 0.0001 and r = 0.49, P < 0.0001 respectively).

CONCLUSIONS

This study performed on healthy subjects showed that pulse pressure amplification is related to body fatness over a wide age range. Percentage body fat is significantly associated with augmentation pressure, a component of central pulse pressure.     

Effectiveness of a medication reconciliation project conducted by PharmD students

Objectives

This study evaluated the effectiveness of a medication reconciliation program conducted by doctor of pharmacy (PharmD) students during an advanced pharmacy practice experience.

Methods

Patients admitted to medicine or surgery units at 3 hospitals were included. Students were instructed to interview each patient to obtain a medication history, reconcile this list with the medical chart, and identify and solve drug-related problems.

Results

Eleven students reconciled medications for 330 patients over 10 months and identified 922 discrepancies. The median number of discrepancies found per patient was 2, and no discrepancies were found in 25% of the cases. In cases in which discrepancies were identified, a greater number of medications had been prescribed for the patient (7.9 ± 4.0 medications compared to 5.4 ± 3.9 medications; p < 0.05). The students completed 59 interventions. Differences were found in the numbers of discrepancies and drug-related problems that different students at different sites identified (p < 0.05).

Conclusions

Pharmacy students provided a valuable service to 3 community hospitals. The students improved the quality of patient care by identifying and solving significant drug-related problems, identifying drug allergy information, and resolving home and admission medication discrepancies.     

Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

AIMS

To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects.

METHODS

Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide.

RESULTS

The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P < 0.0002), but there was no significant difference (P = 0.36) in N-demethylation. Similar changes in plasma metabolic ratios were also found. In plasma, compared with those maintained on buprenorphine, the methadone-maintained subjects had increased codeine and norcodeine concentrations (P < 0.004), similar morphine (P = 0.72) and lower morphine-3- and -6- and codeine-6-glucuronide concentrations (P < 0.008).

CONCLUSION

Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6.     

High dose methotrexate chemotherapy: pharmacokinetics, folate and toxicity in osteosarcoma patients

AIMS

To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy.

METHODS

MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma patients (288 cycles) and AUC (area under the blood concentration–time curve) was calculated. Pretreatment concentrations of folate in serum (S) and erythrocytes (ER) were determined. Hepatic, renal and haematological toxicities, assessed by routine laboratory parameters, as well as mucositis were graded according to National Cancer Institute Common Terminology Criteria for adverse events (CTCAE v.3.0). Dermatitis and pleuritis were reported as occurred or not.

RESULTS

S- and ER-folate pretreatment concentrations increased significantly with increasing number of HD MTX cycles (P < 0.001). ER-folate pretreatment concentrations were higher among males (median 610 nmol l⁻¹, 95% CI 550, 680) compared with females (median 465 nmol l⁻¹, 95% CI 430, 520, P < 0.001), but showed no correlation with MTX or 7-OH-MTX pharmacokinetics. We found correlations between alanine aminotransferase peak concentration (ALAT_max) and clearance of MTX (P < 0.001), gender (P < 0.001), age (P < 0.001) and 7-OH-MTX concentrations (P < 0.001), the latter being the main factor influencing ALAT_max.

CONCLUSION

Our results suggest that 7-OH-MTX is involved in the development of HD MTX hepatic toxicity and that young female patients are most affected.     

Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone

AIM

The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone.

METHODS

A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated.

RESULTS

Paroxetine alone reduced the area under concentration–time curve (AUC(0,0–48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,∞) of oxycodone increased by 2.9-fold (P < 0.001), and its C_max by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo.

CONCLUSIONS

Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially.     

Exploring epistatic relationships of NO biosynthesis pathway genes in susceptibility to CHD

Aim:

To assess the epistatic relationships of nitric oxide (NO) biosynthesis pathway genes in susceptibility to coronary heart disease (CHD).

Methods:

A total of 2142 subjects enrolled in two case-control studies was genotyped for 7 single-nucleotide polymorphisms (SNP) within NO biosynthesis pathway genes using TaqMan assays. The association analyses were performed at both SNP and haplotype levels. Two-way SNP-SNP interactions and high-order interactions were tested using multiple unconditional logistic regression analyses and generalized multifactor dimensionality reduction (GMDR) analyses, respectively.

Results:

Two alleles (rs1049255*C and rs841*A) were identified that were significantly associated with increased risk of CHD after adjusting for all confounders (OR=1.21, 95% CI: 1.06−1.39, combined P=0.001, P_corr=0.007 and OR=1.30, 95% CI 1.12−1.50, combined P<0.001, P_corr<0.001, respectively). Significant two-way SNP–SNP interactions were found between SNP rs2297518 and these two significant polymorphisms, affecting the risk of CHD (P<0.001 for both). No significant high-order interactions were identified.

Conclusion:

The results suggested that two-way SNP–SNP interactions of polymorphisms within NO biosynthesis pathway genes contribute to CHD risk.     

Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren

AIM

The aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren.

METHODS

In a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h.

RESULTS

Orange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%, P < 0.001) and 84% (95% CI 72%, 91%, P < 0.001), and the area under the plasma aliskiren concentration–time curve (AUC) by 62% (95% CI 47%, 72%, P < 0.001) and 63% (95% CI 46%, 74%, P < 0.001), respectively, but had no significant effect on its elimination half-life or renal clearance. The decreases in aliskiren AUC by orange and apple juice correlated with aliskiren AUC during the water phase (r = 0.98, P < 0.001). Plasma renin activity was 87% and 67% higher at 24 h after aliskiren during the orange juice and apple juice phases, respectively, than during the water phase (P < 0.05).

CONCLUSIONS

Orange juice and apple juice greatly reduce the plasma concentrations and renin-inhibiting effect of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided.     

Psychometric evaluation of a self-medication assessment tool in an elderly population

Background:

Most community-dwelling older adults are engaged in medication self-management activities. Deviation in these activities can lead to adverse outcomes for patients and an increased burden on the health care system. Successful medication self-management involves a complex interaction among cognitive, functional, and psychosocial variables. Several assessment instruments have been developed, but there remains a need for an effective and comprehensive tool.

Objective:

To evaluate the psychometric properties (inter-rater reliability, test–retest reliability, and validity), as well as the usability, of the Self-Medication Assessment Tool (SMAT), an instrument designed to measure elderly patients’ ability to manage their medications.

Methods:

The study enrolled patients 65 years of age or older who were living independently and were admitted to family medicine beds in a community hospital in eastern Canada. Three subsamples of the population were identified. The inter-rater reliability group was videotaped and scored independently by 2 pharmacists. The test–retest reliability group was tested with the SMAT and was retested with the same tool a week later. The usability group was interviewed after using the SMAT to determine their satisfaction. Standard neuropsychological measures (Cognitive Competency Test, clock-drawing test, and Mini Mental State Examination [MMSE]) were used to determine convergent and divergent validity. Pill counts, refill rates, and use of adherence aids or reminders before study enrolment were used as measures of concurrent validity.

Results:

A total of 121 patients (mean age 81.5 years) were enrolled. The scales of the SMAT were determined to have good internal consistency and high inter-rater and test–retest reliability. Convergent validity was evidenced by the high positive correlation between the functional scale of the SMAT and the results of the clock-drawing and Cognitive Competency tests (p < 0.01) and between the cognitive and recall scales of the SMAT and the results of the clock-drawing test (p < 0.05), the MMSE (p < 0.01), and the Cognitive Competency Test (p < 0.01). Patients reported being highly satisfied with their experience.

Conclusion:

The SMAT is a practical, reliable, comprehensive instrument with demonstrated convergent validity, strong patient acceptability, and various internally consistent scales that assess multiple dimensions of elderly patients’ ability to self-manage their medications. Further testing is required to show that the SMAT correlates with medication adherence.     

Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-KB pathway in primary rat microglia

Aim:

To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia.

Methods:

Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 μg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein (MCP-1) was measured with ELISA. Protein expression of the nuclear factor-κB (NF-κB) p65 subunit, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was detected with immunocytochemistry 1 h or 24 h after LPS treatment.

Results:

LIG showed a concentration-dependent anti-inflammatory effect in LPS-activated microglia, without causing cytotoxicity. Pretreatment with LIG at 2.5, 5, 10, and 20 μmol/L decreased LPS-induced NO production to 75.9%, 54.4%, 43.1%, and 47.6% (P<0.05 or P< 0.01), TNF-α content to 86.2%, 68.3%, 40.1%, and 39.9% (P<0.01, with the exception of 86.2% for 2.5 μmol/L LIG), IL-1β content to 31.5%, 27.7%, 0.6%, and 0% (P<0.01), and MCP-1 content to 84.4%, 50.3%, 45.1%, and 42.2% (P<0.05 or P<0.01), respectively, compared with LPS treatment alone. LIG (10 μmol/L) significantly inhibited LPS-stimulated immunoreactivity of activated NF-κB, COX-2, and iNOS (P<0.01 vs LPS group).

Conclusion:

LIG exerted a potent anti-inflammatory effect on microglia through inhibition of NF-κB pathway. The data provide direct evidence of the neuroprotective effects of LIG and the potential application of LIG for the treatment of the neuroinflammatory diseases characterized by excessive microglial activation.     

Anticholinergic and sedative medications exposure in older patients: a cross-sectional study

International Journal of Clinical Pharmacy - Background The Drug Burden Index is a risk assessment tool used to quantify anticholinergic and sedative medications burden of older patients. There...     

Association of serum omentin-1 levels with coronary artery disease

Aim:

Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD.

Methods:

One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated.

Results:

Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08±61.43 ng/mL; SAP, 155.41±66.89 ng/mL; control, 254.00±72.9 ng/mL; P<0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P<0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=−0.17, P<0.05) and serum IL-6 concentration (r=−0.19, P<0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD.

Conclusion:

The findings suggest that serum concentrations of omentin-1 are related to CAD.     

Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle

Aim:

To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at ɛ-AChR and γ-AChR.

Methods:

Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing ɛ-AChR or γ-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique.

Results:

NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 μmol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC₅₀) values (VEC: from 11.2 to 39.2 nmol/L, P<0.01; ATR: from 24.4 to 129.0 nmol/L, P<0.01; ROC: from 37.9 to 101.4 nmol/L, P<0.01). In HEK293 cell expression system, ATR was less potent at γ-AChR than ɛ-AChR (IC₅₀ values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC₅₀ values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at γ-AChR than ɛ-AChR (IC₅₀ values: 22.3 vs 33.5 nmol/L, P<0.05).

Conclusion:

Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes.     

Pharmacy-Based Medication Reconciliation Program Utilizing Pharmacists and Technicians: A Process Improvement Initiative

Background:

Pharmacists and pharmacy technicians have an opportunity to impact the quality of the medication histories and improve patient safety by ensuring accurate medication lists are obtained and complete reconciliation has occurred with the admission medication orders by owning the admission medication reconciliation process.

Objective:

To compare the quality of a pharmacy-based medication reconciliation program on admission utilizing pharmacists and technicians to the usual multidisciplinary process.

Methods:

This was a retrospective chart review process improvement study at a 186-bed tertiary care inpatient facility. Primary outcomes included both the accuracy of pre-admission medications listed and the reconciliation of those medications with admission inpatient orders. Technicians obtained patient medication histories. Pharmacists checked the technician-obtained medication histories and ensured reconciliation of those medications with admission orders.

Results:

Medication accuracy increased from 45.8% to 95% per patient (P < .001) and medication reconciliation increased from 44.2% to 92.8% (P < .001) and remained above benchmark.

Conclusion:

A pharmacy-based medication reconciliation program utilizing both pharmacists and technicians significantly increased the accuracy and reconciliation of medications on admission. These gains were maintained for the duration of the 6-month period studied and beyond per continued process improvement data collection.     

Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis

BACKGROUND AND PURPOSE

Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis.

EXPERIMENTAL APPROACH

Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE^−/−) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE^−/− mice were supplemented with either telmisartan (20 mg·kg⁻¹·day⁻¹), ramipril (2.5 mg·kg⁻¹·day⁻¹) or the combination thereof.

KEY RESULTS

Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE^−/− mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE^−/− mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade.

CONCLUSIONS AND IMPLICATIONS

Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE^−/− via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly.     

Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure

AIMS

To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine.

METHODS

A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h.

RESULTS

With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 ± 19 vs. 15 ± 9 ng ml⁻¹; difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration–time curve was almost three times higher [885 ± 560 vs. 304 ± 84 ng h ml⁻¹; difference (95% CI) 581 (205, 957), P < 0.05]; half-life was prolonged by 63% [21.1 ± 6.2 vs. 12.9 ± 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 ± 0.77 vs. 2.25 ± 0.66 l h⁻¹ kg⁻¹; difference (95% CI) −1.13 (−1.80, −0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=−0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects.

CONCLUSIONS

Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF.     

Pilot of a National Inpatient Medication Chart in Australia: improving prescribing safety and enabling prescribing training

AIMS

To establish whether a standard national inpatient medication chart (NIMC) could be implemented across a range of sites in Australia and reduce frequency of prescribing errors and improve the completion of adverse drug reaction (ADR) and warfarin documentation.

METHODS

A medication chart, which had previously been implemented in one state, was piloted in 22 public hospitals across Australia. Prospective before and after observational audits of prescribing errors were undertaken by trained nurse and pharmacist teams. The introduction of the chart was accompanied by local education of prescribers and presentation of baseline audit findings.

RESULTS

After the introduction of the NIMC, prescribing errors decreased by almost one-third, from 6383 errors in 15 557 orders, a median (range) of 3 (0–48) per patient to 4293 in 15 416 orders, 2 (0–45) per patient (Wilcoxon Rank Sum test, P < 0.001). The documentation of drugs causing previous ADRs increased significantly from 81.9% to 88.9% of drugs (χ² test, P < 0.001). The documentation of the indication for warfarin increased from 12.1 to 34.3% (χ² test, P = 0.001) and the documentation of target INR increased from 10.8 to 70.0% (χ² test, P < 0.001) after implementation of the chart.

CONCLUSIONS

National implementation of a standard medication chart is possible. Similar reduction in the rate of prescribing errors can be achieved in multiple sites across one country. The consequent benefits for patient care and training of staff could be significant.     

Validation of the cantharidin-induced skin blister as an in vivo model of inflammation

AIM

Pharmacological profiling techniques, such as the cantharidin-induced skin blister, may be used to assess the anti-inflammatory properties of novel drugs. However, no data are available on the reproducibility of this technique or on the blocking effect of anti-inflammatory drugs, such as anti-TNF and corticosteroids.

METHODS

A group of 30 healthy subjects were randomized into three parallel groups treated with placebo, oral methylprednisolone 20 mg day⁻¹ for 7 days or anti-tumour necrosis factor (TNF) (adalimumab, Humira®, Abbott) 40 mg s.c. single dose. A first blister was induced at baseline and collected, immediately before the start of treatment and a second blister was obtained 7 days after the start of treatment. The total number of cells, the cell viability and the differential cell count were evaluated by two independent observers, who were blind to treatment. anova was used to compare change from baseline among the three groups before pairwise comparisons.

RESULTS

Among the placebo group, there was no significant difference in the total cell count, neutrophils, eosinophils and monocytes between day 1 and day 7. Methylprednisolone inhibited the eosinophil influx in mean % (95% CI) (−1.0 (−1.7, −0.3); P < 0.02) and absolute (P < 0.02) values, while anti-TNF inhibited the neutrophil influx in mean % (95% CI) (−19.3 (−29.5, −9.1); P < 0.01) and absolute (P < 0.05) values.

CONCLUSIONS

The cantharidin-induced skin blister is a safe, well tolerated and reproducible procedure. Pre-treatment with anti-TNF or methylprednisolone inhibited the neutrophilic or eosinophilic trafficking, respectively. It could be useful in profiling anti-inflammatory drugs regarding their effects on the cellular inflammatory response.