Comparison of pharmacists' scoring of fall risk to other fall risk assessments.

OBJECTIVES: Given their professional education and participation within the health care system, pharmacists are ideal candidates to assess drug-associated fall risk for patients. The purpose of this investigation was to determine whether pharmacists can quantitatively differentiate individuals who reported falling within the previous year (fallers) from those who do not (nonfallers), and to compare the pharmacists' evaluation with 2 recently published fall risk assessments. DESIGN: Cross-sectional design of pharmacists' assessments of fall risk. SETTING AND PARTICIPANTS: This is a cross-sectional study where 6 licensed pharmacists evaluated patient records from Wave 1 of the National Social Life, Health and Aging Project dataset using generic drug list (drug counts), age, and body mass index to generate a Pharmacist Risk Score (PRS) based on these variables. Pharmacists were allowed to use drug information resources and were provided with a simple 5-point scale to assist them in scoring patients. OUTCOME MEASURES: The main outcome measure of this study was a comparison of the following fall risk assessments (PRS, drug counts, Medication-Based Index of Physical Function, Quantitative Drug Index, and Timed Up and Go [TUG]) capacity to differentiate fallers from nonfallers. RESULTS: Each fall risk assessment was highly correlated (P < 0.001) with the number of reported falls. Drug-associated fall risk assessments were highly correlated (P < 0.001) with each other, but not with TUG. Each fall risk assessment differentiated fallers from nonfallers based on logistic regression (P ≤ 0.001). Receiver operating characteristic (ROC) curve analysis was significant (P ≤ 0.002) for each assessment. The comparison of ROC area under the curve for the fall risk assessments found no significant difference between the PRS and other assessments. CONCLUSION: Fall risk assessment by pharmacists was comparable with other fall risk assessments in distinguishing fallers from nonfallers.

Visual biofeedback training reduces quantitative drugs index scores associated with fall risk.

OBJECTIVE: Drugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant's drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean. RESULTS: The QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (- 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation. Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016.

Influences of Age, Obesity, and Adverse Drug Effects on Balance and Mobility Testing Scores in Ambulatory Older Adults.

BACKGROUND AND PURPOSE: The adverse effects of drugs may influence results on tests of mobility and balance, but the drug-specific impact is not identified when using these tests. We propose that a quantitative drug index (QDI) will assist in assessing fall risk based on these tests, when combined with other fall risk variables. METHODS: Fifty-seven community-dwelling older adults who could walk independently on a treadmill and had Mini-Mental State Examination (MMSE) scores equal to or greater than 24 participated. Mobility and balance outcome measures included the Balance Evaluation Systems Test (BESTest), Berg Balance Scale (BBS), Timed Up and Go (TUG) and cognitive dual task TUG (TUGc). Fall history, current drug list, and Activity-Specific Balance Confidence (ABC) scale scores were also collected. Body mass index (BMI) was calculated. The QDI was derived from the drug list for each individual, and based on fall-related drug adverse effects. Multiple linear regression analyses were conducted using age, BMI, and QDI as predictor variables for determining mobility and balance test scores, and ABC scale scores. Subsequently, participants were divided into (QDI = 0) low-impact drug group (LIDG) and (QDI > 0) high-impact drug group (HIDG) for Mann-Whitney 2-group comparisons. RESULTS: Age, BMI, and QDI were all significant (P < .001) independent variables in multiple regression analyses for mobility and balance test scores, but not for the ABC scale. Separately, the 2 group comparisons for the BESTest, BBS, TUG, and TUGc demonstrated that HIDG scored significantly (P < .05) worse on these tests compared with the LIDG. Drug counts were also significantly higher for the HIDG than for the LIDG. In contrast, age, BMI, MMSE, and reported falls in the last 12 months were not significantly different between groups. CONCLUSION: Age, BMI, and QDI-all contributed independently to the mobility and balance test scores examined, and may provide health care professionals a screening tool to determine whether additional mobility and balance testing is required. In addition, the QDI is a more precise marker of adverse effects of drugs compared with drug counts, as the latter does not quantitate the influence of drugs on physiologic function.

Development and evaluation of the medication-based index of physical function (MedIP).

Background: the development of an objective and comprehensive drug-based index of physical function for older adults has the potential to more accurately predict fall risk. Design: the index was developed using 862 adults (ages 57-85) from the National Social Life, Health, and Aging Project (NSHAP) Wave 1 study. The index was evaluated in 70 adults (ages 51-88) from a rehabilitation study of dizziness and balance. Methods: the prevalence among 601 drugs for 1,694 side effects was used with fall history to determine the magnitude of each side effect's contribution towards physical function. This information was used to calculate a Medication-based Index of Physical function (MedIP) score for each individual based on his or her medication profile. The MedIP was compared to the timed up and go (TUG) test as well as drug counts using receiver operating characteristic (ROC) analysis. The associations between various indices of physical function and MedIP were calculated. Results: within the NSHAP data set, the MedIP was better than drug counts or TUG at predicting falls based on ROC analysis. Using scores above and below the cutpoint, the MedIP was a significant predictor of falls (OR = 2.61 [95% CI 1.83, 3.64]; P < 0.001). Using an external data set, it was shown that the MedIP was significantly correlated with fall number (P = 0.044), composite physical function (P = 0.026) and preferred gait speed (P = 0.043). Conclusion: the MedIP has the potential to become a useful tool in the healthcare and fall prevention of older individuals.

Exacerbation of celecoxib-induced renal injury by concomitant administration of misoprostol in rats.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12 ± 0.05 µmol/min/100 g) and misoprostol+celecoxib groups (0.07 ± 0.02 µmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65 ± 0.02 vs. 0.35 ± 0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61 ± 0.06 vs. 0.37 ± 0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol.

A Subgroup Analysis of the Impact of Self-testing Frequency on Examination Scores in a Pathophysiology Course.

OBJECTIVE: To determine if the frequency of self-testing of course material prior to actual examination improves examination scores, regardless of the actual scores on the self-testing. METHODS: Practice quizzes were randomly generated from a total of 1342 multiple-choice questions in pathophysiology and made available online for student self-testing. Intercorrelations, 2-way repeated measures ANOVA with post hoc tests, and 2-group comparisons following rank ordering, were conducted. RESULTS: During each of 4 testing blocks, more than 85% of students took advantage of the self-testing process for a total of 7042 attempts. A consistent significant correlation (p≤0.05) existed between the number of practice quiz attempts and the subsequent examination scores. No difference in the number of quiz attempts was demonstrated compared to the first testing block. Exam scores for the first and second testing blocks were both higher than those for third and fourth blocks. CONCLUSION: Although self-testing strategies increase retrieval and retention, they are uncommon in pharmacy education. The results suggested that the number of self-testing attempts alone improved subsequent examination scores, regardless of the score for self-tests.

Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury.

Lidocaine iontophoresis mediates analgesia in lateral epicondylalgia treatment.

BACKGROUND AND PURPOSE: Iontophoresis transcutaneously delivers anti-inflammatory and analgesic drugs for the treatment of musculoskeletal dysfunction. Lidocaine is a local anaesthetic with analgesic but no anti-inflammatory properties. The purpose of this investigation was to examine the clinical use of lidocaine iontophoresis-mediated analgesia in a larger treatment algorithm for five patients with lateral humeral epicondylalgia. METHOD: The investigation was a case series design of five subjects, aged 52 (+/- 6) years, with epicondylalgia of 12-393 days' duration. At each treatment session, the patients received cryotherapy, cross-fibre massage and passive stretch. Between sessions analgesia was provided by an 80 mA-min low-current, long-duration lidocaine iontophoresis (LI) over a 24-hour period. Patients were treated on an every-other-day basis for a total of three treatment sessions. Clinical improvements were determined by triplicate measurements of dolorimetric force over the affected epicondyle prior to treatment 1 (baseline), prior to sessions 2 and 3, and one week following the last session. RESULTS: Patients demonstrated an increasing tolerance to dolorimetric force application prior to the next session. The force values prior to session 2 (3.1 (+/- 1.1) Newton (N)) and one week following the third session (3.4 (+/- 0.5) N) were significantly improved from the baseline values (2.1 (+/- 0.9) N). CONCLUSIONS: Pain associated with lateral epicondylalgia decreased, and function improved in all patients at the final measurement. One patient returned during the 90-day follow-up period to seek additional medical attention. This investigation documents the potential for analgesia provided by LI in the rehabilitation process of musculoskeletal dysfunction.

The influence of voluntary tonic EMG level on the vestibular-evoked myogenic potential.

Vestibular-evoked myogenic potentials (VEMPs) are proposed as a reliable test to supplement the current vestibular test battery by providing diagnostic information about saccular and/or inferior vestibular nerve function. VEMPs are short-latency electromyograms (EMGs) evoked by high-level acoustic stimuli and recorded from surface electrodes over the tonically contracted sternocleidomastoid muscle. VEMP amplitude is influenced by the EMG level, which must be controlled. This study examined the ability of subjects to achieve the EMG target levels over a range of target levels typically used during VEMP recordings. In addition, the influence of target EMG level on the latency and amplitude of the click- and tone-evoked VEMP was examined. The VEMP amplitude increased as a function of EMG target level, and the latency remained constant. EMG target levels ranging from 30 microV to 50 microV are suggested for clinical application of the VEMP.

Effects of iontophoresis current magnitude and duration on dexamethasone deposition and localized drug retention.

BACKGROUND AND PURPOSE: Iontophoresis is a process that uses bipolar electric fields to propel molecules across intact skin and into underlying tissue. The purpose of this study was to describe and experimentally examine an iontophoresis drug delivery model. SUBJECTS AND METHODS: A mechanistic model describing delivery was studied in vitro using agarose gels and was further tested in vivo by evaluation of cutaneous vasoconstriction following iontophoresis in human volunteers. RESULTS: In vitro cathodic iontophoresis at 4 mA and 0.1 mA each delivered dexamethasone/dexamethasone phosphate (DEX/DEX-P) from a 4-mg/mL donor solution to a depth of 12 mm following a 40 mA minute stimulation dosage. Delivery of DEX/DEX-P to at least the depths of the vasculature in humans was confirmed by observation of cutaneous vasoconstriction. This cutaneous vasoconstriction was longer lasting and greater in magnitude when using low-current, long-duration (approximately 0.1 mA) iontophoresis compared with equivalent dosages delivered by higher-current, shorter-duration (1.5-4.0 mA) iontophoresis. DISCUSSION AND CONCLUSION: From data gathered with the gel model, the authors developed a model of a potential mechanism of drug depot formation following iontophoresis. The authors believe this drug depot formation to be due to exchange of drug ions for chloride ions as the ionic current carriers. Furthermore, diffusion, not magnitude of current, appears to govern the depth of drug penetration. Although the authors did not address the efficacy of the drug delivered, the results of human experiments suggest that current magnitude and duration should be considered as factors in treating musculoskeletal dysfunctions with iontophoresis using DEX/DEX-P at a concentration of 4 mg/mL.

Quantification of total dexamethasone phosphate delivery by iontophoresis.

The total amount of dexamethasone phosphate transferred into the human body as a function of iontophoresis has not previously been determined, despite its widespread clinical use in the treatment of localized inflammation. The objective of this study was to document the optimal parameters required for clinical iontophoresis of dexamethasone phophate. Results were achieved by the experiment of in vitro evalutations of dexamethasone phosphate iontophoresis and by in vivo estimations of drug amounts (milligrams) iontophoresed into healthy human volunteers. The in vitro evaluations were conducted to quantify total dexamethasone phosphate amounts transferred as a function of dosage (milliAmp-minutes), to evaluate the efficiency of the delivery based on dexamethasone phosphate only (pure) donor solutions compared with dexamethasone phosphate + salts (coformulated) donor solutions, and to compare the delivery from the negative electrode (cathode) with that from the positive electrode (amode). The in vivo drug amounts were estimated by the use of the formulation conditions determined from the in vivo testing. The in vitro evaluations were conducted with side-by-side glass diffusion cells, which measured iontophoretic and passive delivery across an ultrafiltration membrane. The in vivo experiments were conducted on five healthy human volunteers who were wearing a low-voltage iontophoreses system. Total drug delivery was ascertained by the difference between the initial drug load and a final residual amount determined by extraction. The in vitro results demonstrated increased dexamethasone phosphate delivery with higher iontophoretic dosages and with the pure dexamethasone phosphate formulation. Delivery from the anode was significantly lower than that from the cathode. After an 80-mA-minute drug-delivery was administered, the in vivo iontophoretic delivery was measured to be 1.40 +/- 0.23 mg, and the corresponding passive delivery was 0.26 +/-0.16 mg. The in vitro experiments confirm iontophoretic delivery of dexamethasone phosphate across artificial membranes, and the in vivo experiments suggest that drug is delivered into human skin.

Failure to detect dexamethasone phosphate in the local venous blood postcathodic lontophoresis in humans.

STUDY DESIGN: A single-blind, 2-factor (4 treatments by 8 time points) repeated-measures study design. OBJECTIVE: To analytically determine dexamethasone and dexamethasone phosphate concentrations in plasma derived from proximal effluent venous blood, following cathodic iontophoresis. METHODS AND MEASURES: Six volunteers received the following dexamethasone phosphate (2.5 ml, 4 mg/ml) treatments to their wrists on separate occasions: cathodic iontophoresis (4 mA, 10 minutes or 4 mA, 20 minutes), passive application (10 or 20 minutes). Plasma samples from the ipsilateral antecubital vein were obtained 10 minutes prior to and half way through the treatment (5 or 10 minutes), at the end of the treatment (10 or 20 minutes), and posttreatment (15, 30, 60, 90, and 120 minutes). The present investigation examined: (1) the sensitivity and linearity of extraction and analysis of dexamethasone and dexamethasone phosphate; (2) the necessity for determining both; and (3) the plasma levels from proximal effluent venous blood following cathodic iontophoresis. RESULTS: The aggregate (n = 18) of the 6-point standard curves were linear for dexamethasone (r > 0.974) and dexamethasone phosphate (r > 0.829). In vitro dephosphorylation of dexamethasone phosphate to dexamethasone occurred in plasma at 37 degrees C and during freeze-thaw. Measurable dexamethasone or dexamethasone phosphate concentrations were absent at all time points and under all conditions in the human subjects. CONCLUSIONS: These results demonstrate the sensitivity of the current assay and the need for evaluating both forms of the drug, as in vitro dephosphorylation results in the presence of dexamethasone and dexamethasone phosphate in samples. Absence of measurable dexamethasone or dexamethasone phosphate in the proximal effluent venous blood may require re-evaluation of the extent of drug delivery during the clinical iontophoresis of dexamethasone phosphate.