Deborah W. Robin

Rational Use of Benzodiazepines in the Elderly

SummaryIn the 40 years since the introduction of benzodiazepines into clinical practice, considerable controversy has surrounded their use. While there is little evidence to suggest widespread abuse or long term use in most age groups, benzodiazepines continue to be widely prescribed to older adults in both community and long term care settings. Several studies have described an increased sensitivity to the clinical effects and toxicity of benzodiazepines in older adults. However, it is unclear whether these observations are attributable to age-related changes in benzodiazepine pharmacokinetics or pharmacodynamics.Benzodiazepines are the safest and most effective agents available for the pharmacological management of symptoms of anxiety and insomnia. However, the acute administration of benzodiazepines is associated with impairments in cognition, memory, coordination and balance, and long term use, even at therapeutic dosages, has been associated with symptoms of withdrawal upon abrupt discontinuation. Therefore, it is essential that the practitioner develop a treatment plan when utilising these agents to treat older patients. This plan may also involve the implementation of psychotherapy or other nonpharmacological modalities in the management of anxiety or insomnia. Although we recommend initiating benzodiazepines using the lowest available dosage, older patients should be treated with enough drug to produce a therapeutic response. For most clinical situations of anxiety or insomnia, we recommend prescribing limited quantities (e.g. a 2-week supply with a return visit for re-evaluation of effectiveness and adverse effects) of a drug with a short elimination half-life. Persistent anxiety or insomnia in the elderly may require a medical and possibly psychiatric evaluation. If benzodiazepines are used continuously for 6 weeks or longer, we recommend a gradual taper over 2 to 12 weeks with frequent follow-up to evaluate for signs of withdrawal or the return of symptoms.

Simultaneous measurement of body center of pressure and center of gravity during upright stance. Part I: Methods

Abstract Clinical and experimental assessments of balance use measures of center of pressure (COP) excursion to quantify postural stability during standing. This assumes that the greater the COP excursions, the greater the imbalance. However, it is the position of the body center of gravity (COG), specifically in relation to the base of support, that determines static stability during upright standing. The reason the COG is frequently ignored is that it cannot be measured directly, whereas the COP is readily obtained from a force platform. We report here on a method for simultaneous measurement of the COP and COG displacements. To compute the COG displacements, an optoelectric imaging system operating in synchrony with a force platform was used to measure the three-dimensional positions of the body joints and body segment endpoints. The COG displacements were then computed from the segment kinematics using subject-specific anthropometric measurements. In Part II of this paper, we compare summary measures of the COP and COG excursions obtained from six subjects during three different upright stances.

Simultaneous measurement of body center of pressure and center of gravity during upright stance. Part II: Amplitude and frequency data

Abstract In this paper (Part II) we present amplitude and frequency data on simultaneously measured excursions of the body center of gravity (COG) and center of pressure (COP). The excursions were measured from six subjects during 10-s trials of three upright postural stances: standing on both legs or double stance with eyes open (DSEO), double stance with eyes closed (DSEC), and standing on one leg or single stance with eyes open (SSEO). This study represents the first attempt to describe the normative characteristics and stance-dependent differences between the anteroposterior and mediolateral components of both the COP and COG signals, measured from multiple individuals by the technique described in Part 1. We quantified the anteroposterior and mediolateral excursions of the COP and COG using amplitude and frequency measures, and their planar excursions using 95% confidence ellipses. Although the COP-based amplitude measures were significantly greater than their COG-based counterparts, the amplitude and frequency measures of both were highly correlated in all stances. The results support the continued use of COP-based measures to quantify impaired balance during upright stance.

Increased baseline sway contributes to increased losses of balance in older people following triazolam

OBJECTIVE: Although it has been stated frequently that older people are more sensitive to benzodiazepines, the relative roles of impaired baseline performance, impaired elimination, and altered responsiveness have not been defined. We evaluated postural sway and plasma triazolam concentrations after administration of placebo and triazolam 0.375 mg in both young and older healthy subjects.

Triazolam in cirrhosis: Pharmacokinetics and pharmacodynamics

Although it is frequently stated that patients with cirrhosis are more sensitive to benzodiazepines, the relative roles of impaired elimination and altered responsiveness have not been clarified. We evaluated the pharmacokinetics, pharmacodynamics, and sensitivity to triazolam in six patients with clinically stable cirrhosis and six age‐matched control subjects. Our findings show that there were no significant differences between the patients with cirrhosis and the control subjects in any of the pharmacokinetic parameters. Drug effect, measured as postural sway, was also similar in the patients with cirrhosis and control subjects; therefore the ratio of effect area under the curve to concentration area under the curve, a measure of sensitivity, did not differ significantly between the patients with cirrhosis and the control subjects. Because triazolam is metabolized by P4503A, we hypothesized that the effects of cirrhosis on drug metabolism may differ with respect to the specific P450 responsible for the oxidation of this drug. These effects may differ because of the relative sparing of a specific P450 and because of an extrahepatic site of metabolism.

Sensitive assay for triazolam in plasma following low oral doses

At low doses of triazolam currently recommended increased assay sensitivity is required for measurement of low plasma concentrations. A highly sensitive capillary gas chromatographic analytical method with a limit of detection of 0.02 ng/ml was developed and used to describe the pharmacokinetics of triazolam following the oral intake of 0.125, 0.250 and 0.375 mg. Six male subjects were studied with blood sampling at the following times: 0, 15, 30 and 45 min and 1, 1.5, 2.0, 2.5, 3, 4, 5, 6 and 8 h. The mean pharmacokinetic parameters for the three doses, respectively, were as follows: half-life, 2.7 +/- 0.4, 3.2 +/- 0.5 and 3.2 +/- 0.6 h; apparent oral clearance, 302.3 +/- 59.0, 260.2 +/- 67.9 and 328.6 +/- 77.8 ml/min; apparent volume of distribution, 64.3 +/- 9.6, 62.0 +/- 12.6 and 73.3 +/- 7.7 l; time to maximum concentration, 0.7 +/- 0.2, 0.6 +/- 0.1 and 0.8 +/- 0.3 h; maximum concentration, 2.2 +/- 0.3, 4.3 +/- 0.6 and 5.0 +/- 0.5 ng/ml; and the area under the concentration-time curve (AUC) up to 8 h, 6.8 +/- 1.2, 16.8 +/- 2.9 and 19.6 +/- 3.5 ng/ml h; and AUC extrapolated to infinity, 8.5 +/- 1.7, 21.4 +/- 4.4 and 26.3 +/- 7.2 ng/ml h. There were no significant differences in the half-life, clearance, volume of distribution and time to maximum concentration among the three doses. The AUC was significantly different on the three occasions and was linearly correlated with dose: r = 0.64 (p less than 0.005).

Drugs and postural sway: quantifying balance as a tool to measure drug effects

Research aimed at modeling the relationship of the center of gravity (COG) to the center of pressure (COP) and testing alternative clinically useful measures of postural stability that are based on the COG and COP is described. Postural sway is spontaneous involuntary body movements that result from the neuromuscular corrective mechanisms acting to preserve static posture, such as standing or sitting. The second aim of the research is to implement clinically relevant measures of postural stability, such as the limits of stability, in the context of the ongoing examination of the effects of drugs on balance. Preliminary results and directions of future research are outlined.<<ETX>>

RAC Attack—Medicare Recovery Audit Contractors: What Geriatricians Need to Know

Knowledge of Medicare policies and procedures is integral to the practice of geriatric medicine. Within the past several years, there has been a focus on Medicare fraud, abuse, and waste in healthcare spending. One program, Medicare Recovery Audit Contractors (RAC), has recently been launched to indentify improper payments by performing postpayment reviews of Medicare Part A and Part B claims. During the program pilot project in only three states, more than

Post-acute Care for Rheumatologists

1 billion in incorrect payments were identified, with the overwhelming majority being overpayments that had to be returned to the Medicare Trust Fund. In 2006, Congress mandated that the RAC program be rolled out nationwide, which is ongoing. The audit focuses on documentation of medical necessity for inpatient admission and the 3‐day qualifying stay for skilled nursing care, important concerns for geriatricians. This article describes the RAC program and target areas for payment recoupment, denials management, and provider preparation.

Triazolam pharmacokinetics and pharmacodynamics in Caucasians and Southern Asians: ethnicity and CYP3A activity

Post-acute care encompasses a wide range of health care services that share the goal of restoring recently hospitalized patients to the highest level of functioning possible. Post-acute care can be provided in a long-term acute care hospital, inpatient rehabilitation facility, skilled nursing facility, or home using home health care. While a range of similar nursing and rehabilitation services can be provided in all settings, admission criteria and payment sources differ. Determining the most appropriate setting for care following hospitalization is an important decision that should be made with input from the patients, their family, the physician, nurses, and rehabilitation therapists.