Update on drug-related problems in the elderly

Updates

The American Journal of Geriatric Pharmacotherapy

Update on Drug-Related Problems in the Elderly M a r y Jo Pugh, RN, PhDI; C a t h e r i n e I. Lindblad, PharmD2; Steven M. Handler, MD, MS3; and Joseph T. Hanlon, PharmD, MS 3'4

I Veterans Health Administration, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 2Department of Experimental and Chnlcal Pharmacology,College of Pharmacy, University of Minnesota and Veterans Affairs Medical Center, Minneapohs, Minnesota, 3Diwslon of Geriatric Medicine, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,and "4Centerfor Health Equity Research and Promotion,Veterans Administration Pittsburgh Health Care System,Pittsburgh, Pennsylvania

There has been a plethora o f recent articles on the sub]ect o f drug-related problems in the elderly. In this issue, we have selected 8 articles for review. Other recent articles o f interest are listed at the end o f this rcv1cvG

EPIDEMIOLOGY INAPPROPRIATE

OF PRESCRIBING

Early in 2005, Zahn et al 1 reviewed the prevalence o f d r u g - d r u g and drug-disease interactions in elderly outpatients. Given the scarcity o f data on drug-disease interactions in the elderly, this discussion will focus specifically on the study findings relating to this topic. The investigators assessed the prevalence as well as the potential clinical implications o f drug-disease interactions. Data for the study came from 2 surveys conducted from 1995 to 2000 by the National Center for Health Statistics, the National Ambulatory Medical Care Survey, and the National Hospital Ambulatory Medical Care Survey. Medication data were collected at each outpatient visit for up to 6 prescription or nonprescription medications prescribed, administered, injected, or provided at the visit. The list o f d r u g - d r u g and drug-disease interactions used in the study came from Beers 2 and McLeod et al, 3 well-known groups from the United States and Canada, respectively. The investigators categorized the interactions as being o f high, moderate, or low clinical significance. A total o f 70,203 visits by elderly patients were included in the study) Drug-disease interactions involving at least 1 prescription medication were identified in 2.58% o f these VlSltS (95% CI, 2.44-2.72). The 2 most c o m m o n drug-disease interactions were the use o f

Acceptedfor publicationAugust3, 2005

j~-blockers in patients with diabetes and the use o f calcium channel blockers in patients with congestive heart failure. Fourteen o f 50 possible drug-disease interactions were not found in the visits studied. The n u m b e r o f drugs prescribed, male gender, and black race were found to be most highly predictive o f inappropriate drug-disease combinations (all, P < 0.05). The investigators noted some hmltatlons to their study. In particular, their estimates were hkely to be conservative because no more than 6 drugs were included; patients may see multiple providers, leading to possible failure to capture all drugs; and only a subset o f all possible drug-disease interactions was studied. A recent study o f drug-disease interactions by Llndblad et al4 applied the same criteria as in the previous study to a group o f frail hospitalized veterans. Individual medications were grouped into therapeutic classes, and diseases were classified using the International Classification o f Diseases. O f the almost 400 patients included, 40.1% had the potential for a d r u g disease interaction. The most c o m m o n potential d r u g disease interactions involved calcium channel blockers in patients with heart failure; aspirin in those with peptic ulcer disease; and r-blockers in those with diabetes mellitus, peripheral vascular disease/Raynaud's disease, or chronic obstructive pulmonary disease. Age >75 years, being married, comorbldlty index, and taking >5 prescription medications were all statistically significantly associated with the potential for a drug-disease interaction ( P < 0.05). The limitations o f this study included its cross-sectional design, small h o m o g e n e o u s sample, and use o f only 2 lists o f explicit criteria for drug-disease interactions.

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These 2 studies found very different prevalence rates o f drug-disease interactions in the elderly; however, the unit o f analysis in the study by Zahn et al 1 was visits, and the unit o f analysis in the study by Llndblad et al4 was persons. Other studies investigating the use o f medications thought to potentially exacerbate underlying diseases in the elderly have found prevalence rates o f drug-disease interactions ranging from 2% to 30% in communlty-dwelhng and hospitalized elderly patients. ~ 8 Further research involving drug-disease interactions, particular chnlcally relevant drug-disease interactions and their impact on health outcomes, will be welcome. References

1 Zahn C, Correa-de-Arau]o R, Blerman AS, et al Subopumal prescnbmg m elderly outpatients Potentially harmful drug~irug and drug-disease combmauons J A m Ger~atr Soc 2005,53 262-267 2 Beers MH Exphclt criteria for determining potentially inappropriate medication use by the elderly An update Arch Intern Med 1997,157 1531-1536 3 McLeod PJ, Huang AR, Tamblyn RM, Gayton DC Defimng mapproprmte practices m prescribing for elderly people A nauonal consensus panel CMAJ 1997,156 385-391 4 Lmdblad CI, Artz MB, Pleper CF, et al Potentml drug-disease interactions m frail, hospltahzed elderly veterans A n n Pharmacother 2005,39 4 1 2 4 1 7 5 Hanlon JT, Schmader ICE, Boult C, et al Use of inappropriate prescnpuon drugs by older people J A m Ger~atr Soc 2002,50 26-34 6 Ihrl
OF

Three recently pubhshed studies examined the association bepa'een exposure to inappropriate drugs, health services utilization, and mortality. 1 3 All 3 found significant relationships between inappropriate prescribing and outcomes; however, each group used a different approach to defining inappropriate drug use, the popu-

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latlon o f interest, and the temporal relationship between inappropriate prescribing and outcomes. Examination o f the differences sheds hght on the extent to which the findings can be generalized. Perrl et al 1 examined inappropriate prescribing in 1117 frail long-term care residents from the Georgia Medicaid population. A medical records review of a 1-month period was conducted to identify patients receiving any drug included in the Beers criteria, 4 in addition to therapeutic duphcannons, drug-disease interactions, and chronic use o f medications intended to address acute symptoms. A dichotomous measure was constructed to identify individuals having any of these components o f inappropriate drug usc. Patlcnts who dlcd or rccclvcd cmcrgcncy or hospital care were classified as having an adverse health event. Loglsnnc regression analyses controlling for demographic characteristics and chnlcal characteristics such as do not resuscitate status, length o f stay, and common disease condlnnons found that patients receiving an inappropriate drug were 2.3 times more likely to have an adverse health outcome compared with patients without inappropriate drug use (95% CI, 1.6-3.4). In the second study, I~arln et al2 examined data for 785 elderly persons (age >75 years) living in the community, assisted living faclhnnes, or nursing homes in Sweden. Complete drug data were obtained from inspection of patients' medllcannon hsts and containers at baseline and from patient interviews. Inappropriate prescribing was defined based on use o f high-severity Beers drugs, therapeunnc duplications, and drug-drug interactions identified as severe in the Swedish drug compendium. Unlike the study by Perri et al, 1 which combined adverse health outcomes into a single outcome measure, this study used separate analyses to determine the impact of inappropriate prescribing on hospitalization and mortality over a 3-year period. The investigators found that after adjusting for demographic characteristics--including education and type o f hying situation (independent, assisted living, nursing h o m e ) - - a n d clinical characteristics (comorbldlty, smoking, independence or dependence in performing a c t i v i t i e s o f daily living [ADL]), being exposed to inappropriate drugs significantly increased the hkchhood of hospitalization (odds ratio [OR] = 2.72; 95% CI, 1 . 6 4 . 5 ) . No association was found with mortality. In the third study, Lau ct al3 used data from the nursing h o m e component o f the Medical Expenditure Panel Survey to examine medication use in 3372 long-term care facility residents aged >65 years. Medication use over a 1-year period, as determined from medicationadministration records and medical charts, was examined. Inappropriate prescribing was defined using the

Updates

3 componcnts o f t h c Bccrs crltcrla4: lnapproprlatc drug usc, drugs with dosc limitations, and drug-dlscasc lntcractions. Indicators for any lnapproprlatc drug usc wcrc crcatcd for cach month. As in thc study by Klarln ct al, 2 thcsc lnvcstlgators pcrformcd scparatc analyscs for hospitalization and mortality outcomcs. Multlvarlatc analyscs o f thc prcdlctcd impact o f cxposurc to lnapproprlatc drugs that controllcd for dcmographlc charactcrlstlcs (cg, agc, scx, racc, Mcdlcald covcragc), clinical charactcrlstlcs (cg, A D L limitations, dcmcntla), and charactcrlstlcs o f thc facllltlCS in which patlcnts rccclvcd carc (cg, accrcdltatlon status, ratio o f rcglstcrcd nurscs to patlcnts) found that cxposurc to lnapproprlatc drugs significantly lncrcascd thc risks for hospitalization ( O R = 1.27; 95% CI, 1.09-1.47) and mortality ( O R = 1.28; 95% CI, 1.05-1.55). Thcsc 3 studlcs provldc ncw cvldcncc that lnapproprlatc drug usc is assoclatcd with ncgatlvc hcalth outcomcs. However, the hmltatlons o f these studies must be taken into account. First, the studies did not use a hst o f drugs to be avoided in the elderly as the sole measure o f mapproprlate prescribing. All the studies included measures o f dose hmltatlons, drug interactions, or other aspects of drug utlhzatlon review (DUR) criteria, such as therapeutic duphcatlon. Second, all the studies included individuals in nursing-home or assisted-hying populations, who are known to be fraller than the ambulatory population. Third, the temporal relationship o f inappropriate prescribing to health outcomes was not well established. O f these 3 studies, Lau et al 3 best established the temporal relationship between inappropriate prescribing and outcomes. Fourth, point estimates were highly variable between the studies, with Lau et al being the smallest and Klarln et al2 being the largest. In fact, in the case of the smaller point estimates, it is not possible to rule out residual confounding, which could explain the association between inappropriate prescribing and health outcomes. Moreover, the prescribing o f high-risk Beers drugs cannot be determined in the study by Lau et al. The combined outcome used in the study by Pert1 et al 1 also makes it difficult to interpret the findings. Finally, none of these studies controlled for the number o f medications received by patients in the analyses predicting hospltahzatlon or mortahty. Analyses that exclude polypharmacy may not adequately control for disease burden, which is also associated with hospltahzatlon and mortahty. Therefore, the use of these drugs could be, at least in part, a proxy for &sease seventy. H o w do these new data compare with previous work? A study by Fu et al~ found a small association between exposure to Beers drugs to avoid in the elderly and self-

The American Journal of Geriatric Pharmacotherapy

rated health in ambulatory elderly patients. Hanlon ct al6 and Flllcnbaum ct al7 found no differences in mortality, functional status, nursing home admission, or number o f outpatient visits in patients receiving mapproprlatc drugs based on the Beers list o f drugs to avoid. However, they found that patients receiving Beers drugs wcrc more hkcly to bc hospltahzcd compared with patients without inappropriate drug exposure ( O R = 1.20; 95% CI, 1.04-1.39), and the risk was lower for patients receiving high-severity drugs on the list than for those receiving low-severity drugs. These investigators also found that older patients who rccclvcd inappropriate drugs as defined by D U R criteria, particularly those with d r u g - d r u g and drug-disease interactions, experienced reductions in their ability to perform ADLs and had more outpatient clinic visits than individuals without exposure to inappropriate drugs. Based on this discussion, we can say that criteria for D U R appear to bc more strongly associated with a variety o f patient outcomes than the Beers list o f generally inappropriate drugs. It is interesting to note that the National Committee on Quality Assurance has recently developed quality measures for inappropriate prescribing in the elderly (based on the list o f drugs to avoid in the updated Beers criteria 8) and for laboratory monitoring o f chronic drug therapy. 9 References

1 Pern M III, Menon AM, Deshpande AD, et al Adverse outcomes associated with inappropriate drug use m nursing homes A n n Plsarmacotlser 2005,39 4 0 5 4 1 1 2 Klarln I, Wlmo A, Fastbom J The association of inappropriate drug use with hospltahsanon and mortahty A population-based study of the very old Drugs Aging 2005 22 69-82 3 Lau DT, ICasper JD, Potter DE, et al Hospltahzatlon and death associated with potentially inappropriate medlcanon prescnpnons among elderly nursing home residents Arch Intern Med 2005,165 68-74 4 Beers MH Exphc~t criteria for determining potennally inappropriate me&canon use by the elderly An update Arch Intern Med 1997,157 1531-1536 5 Fu AZ, Lm GG, Chnstensen DB Inappropriate me&canon use and health outcomes m the elderly J A m Ger, atr Soc 2004,52 1934-1939 6 Hanlon JT, Flllenbaum GG, Kuchlbhatla M, et al Impact of inappropriate drug use on mortahty and funcnonal status m representanve commumty dwelhng elders Med Care 2002,40 166-176 7 Flllenbaum GG, Hanlon JT, Landerman LI~ et al Impact of inappropriate drug use on health services utlhza-

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non among representanve older communlty-dwelhng residents A m J Ger, atr Pharmacother 2004,2 92-101 8 Fmk DM, Cooper JW, Wade WE, et al Updating the Beers criteria for potennally inappropriate me&canon use m older adults Results of a US consensus panel of experts Arch Intern Med 2003,163 2716-2724 9 NCQA Releases HEDIS '~ 2006 New measures address overuse, follow-up Press release, July 7, 2005 Available at h t t p / / v ~ w ncqa org/communmauons/news/HEDIS_ 2006 htm Accessed July 25, 2005 EPIDEMIOLOGY OF ADVERSE DRUG REACTIONS IN THE ELDERLY

Gurwltz et al 1 recently published the results o f a cohort study including all long-stay residents o f 2 academic nursing homes over a 9-month period. The ob3ectlve of the study was to assess the incidence of and risk factors for adverse drug events in the nursing home setting. The severity (less serious, serious, life threatening, or fatal) and preventability o f each adverse drug event was determined. In addition, a case-control study was nested within the prospective study to identify resident-level risk factors for the occurrence o f adverse drug events. Over the period studied, 815 adverse drug events wcrc detected, o f which 42% (342) wcrc considered preventable and thus amenable to intervention. The overall rate o f adverse drug events was 9.8 per 100 resident-months, and the rate o f preventable adverse drug events was 4.1 per 100 resident-months. Errors associated with preventable events occurred most often at the monitoring (80%) and ordering (60%) stages o f the medication-use process. Use o f certain medications increased the risk o f a preventable adverse event. In multivariate analyses, the adjusted O R was 3.4 for patients taking antlpsychotlc agents (95% CI, 2.0-5.9), 2.8 for those taking anticoagulants (95% CI, 1 . 6 4 . 7 ) , 2.2 for those taking diuretics (95% CI, 1 . 2 4 . 0 ) , and 2.0 for those taking antiepileptics (95% CI, 1.1-3.7). The authors concluded that their findings reinforce the nccd to focus on the monitoring and ordering stages to prevent adverse drug events in the nursing home setting. They stated that patients taking antlpsychotlc agents, anticoagulants, diuretics, and antlcpllcptics are at increased risk. This study expands our knowledge o f the incidence and preventability o f adverse drug events in academic nursing homes. The same authors previously performed a cohort study including all long-term care residents o f 18 community-based nursing homes in Massachusetts over a 12-month period. 2 That study identified 546 adverse drug events (1.89 per 100 resident-months) and

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188 potential adverse drug events (0.65 per 100 resident-months). It is curious that the rate of adverse drug events was more than 5 nmcs greater in an academic versus a community-based nursing home. According to the authors, 2 factors accounted for the higher rate of detecnon o f adverse drug events in the academic nursing home. First, the chnlcal pharmacist lnvesngators maintamed a constant presence in the participating nursing homes throughout the study, providing increased access to medical-record information. Second, in addition to periodic reviews o f all medical records for potennal adverse drug events, computer-generated signals were uscd to assist in targcnng mcdlcal rccords for morc intensive rcvlcw. To our knowlcdgc, this is thc first nmc that a cllnlcal-cvcnt m o n i t o r (lC, an automatcd dcclslon-support system that provides feedback to health care professionals bascd on informanon avallablc in an clcctronlc format) has bccn used to help determine the incldcncc o f adverse drug events in the nursing home scmng. References

1 Gurwltz JH, Fmld TS, Judge J, et al The incidence of adverse drug events m two large academm long-term care facllmes A m J M e d 2005,118 251-258 2 Gurwltz JH, Fmld TS, Avorn J, et al Incidence and preventablhty of adverse drug events m nursing homes Am J M e d 2000,109 87-94 INTERVENTIONS TO MODIFY PROBLEMS IN THE ELDERLY

DRUG-RELATED

Holland ct al 1 recently published the results o f a randomlzcd, controlled health services intervention trial involving 872 patients (age >80 years) being discharged from 10 hospitals in the United gangdom. The oblcctlvc o f t h c study was to dctcrmlnc whcthcr homcbascd mcdlcatlon rcvlcw by pharmacists affcctcd hospital rcadmlsslon ratcs among oldcr pcoplc. Onc hundrcd scvcnty-clght control and 234 lntcrvcntlon patlcnts wcrc rcadmlttcd (hazard ratio [HR] = 1.30; 95% CI, 1.07-1.58; P < 0.05). There was a numerically lower but statistically nonsignificant dccrcasc in mortality in thc intcrvcntlon group ( H R = 0.75; 95% CI, 0.521.10) and no significant dlffcrcncc in health-related quality o f llfc. Thc invcstlgators concludcd that thc intcrvcntlon was assoclatcd uath a significantly hlghcr ratc o f hospital admission and no significant improvcmcnt in quality o f life or rcductlon in mortality. Thc findings o f this study arc counterintuitive. H o w can thcy bc cxplalncd? First, problcms rcqulrlng mcdlcal attcntlon in thc hospital wcrc dctcctcd in thc lntcr-

Updates

vcntlon group that might otherwise have led to more serious morbidity. The numerically decreased mortality in the intervention group may support this explanation. Second, information on length o f stay and costs would have been helpful in determining other potential differences between groups. N o information was provided concerning which o f the readmlsslons, if any, were the result o f drug-related problems. Finally, the study did not measure the effect o f the intervention on me&cation adherence or the quality o f prescribing. It is possible, given the probable high rate o f inappropriate prescribing in these patients, that the intervention could have led to improved adherence with inappropriate me&cations and thus resulted in adverse drug reactions and related hospital admissions. Methodologlc problems may limit the conclusions of this study. The results are inconsistent with those of another pharmacist-intervention study. 2 However, i t lS conSlstent V¢lth thC results o f a health services--intervention trial in which intervention patientS discharged from Veterans Affairs hospitals had more primary care physician visits compared with those in the control group. 3 The results o f the study by Holland et al 1 should be viewed cautiously and should not deter health care professionals from using the services o f a clinical pharmacist to optimize me&cation utilization in older adultS. Crotty et al4 recently reported the impact o f the use of a geriamc outreach me&cation advisory service in 109 elderly patientS in residential care in Australia. Five homes were randomized to receive the intervention, and 5 were randomized to the control group. The intervention conSlsted o f me&cation review at a case conference to which the primary care physician was invited, along with a geriatrician, a pharmacist, and a member of the residential home staff. The investigators found that compared with the control group, the intervention group had slgnlficandy improved quality o f prescribing, as measured on the Medication Appropriateness Index (MAI). There were no differences by group status on the secondary measures o f resident behavior and drug costS. The authors concluded that multldlsclphnary case conferences in nursing homes can improve care. The authors should be complimented on several countS. First, the randomization of nursing homes rather than residentS preventS the potential contamination o f control patientS through treatment by the same primary care physicians who cared for intervention patients. Second, the team-consultation approach is novel. It is likely that the improvements in MAI were the result of better communication beva'een the health care professionals responsible for the patient's treatment and the

The AmericanJournal of Geriatric Pharmacotherapy

cxpcrt advlcc ofhcalth professionals with training in gcrlatrlcs. However, the clinical significance of a 4-point improvement in MAI is tmclear. A previous published pilot study found this magnitude o f change in the MAI to be associated with fewer hospitalizations and emergency r o o m visits. 5 Due to itS small sample size, the study was underpowered to determine differences in &stal patient outcomes. Also, no information was provided regarding the cost-effectiveness of the intervention. Finally, it is not clear how this intervention would translate to the United States, where a consultant pharmacist is reqmred by law to conduct monthly drug-regimen reviews. References

1 Holland R, Lenaghan E, Harvey I, et al Does home based me&canon revmw keep older people out of hosp> tap The HOMER randomlsed controlled real BMJ 2005,330 293 Pubhshed onhne January 21, 2005 2 Hanlon JT, Wemberger M, Samsa GP, et al A randomlzed controlled trial of a chmcal pharmacist mtervennon with elderly outpanents with polypharmacy Am J Med 1996,100 4 2 8 4 3 7 3 Wemberger M, Oddone EZ, Henderson WG, for the Veterans Affairs Cooperanve Study Group on Primary Care and Hospital Readmlsslon Does increased access to pnmary care reduce hospital readmlsslons~ N EnglJ Med 1996,334 1441-1447 4 Crotty M, Halbert J, Rowett D, et al An outreach genatnc me&canon advisory servme m resldennal aged care A randomlsed controlled trial of case conferencmg Age Ageing 2004,33 612-617 5 Schmader KE, Hanlon JT, Landsman PB, et al Inappropnate prescnbmg and health outcomes m elderly veteran outpanents Ann Pharmacother 1997,31 529533 OTHER ARTICLES

OF INTEREST

Bennett e L , Nebeker JR, Lyons EA, ct al. The Research on Adverse D r u g Events and Reports (RADAR) project. J A M A . 2005 ;293:2131-2140. Caamano F, Pedone C, Zuccala G, Carbonln P. Soclo-demographlc factors related to the prevalence o f adverse drug reaction at hospital admission in an elderly population. Arch Geronrol Get, art. 2005;40: 45-52. Catcrlno JM, E m o n d JA, Camargo CA Jr. Inappropriate me&cation administration to the acutely ill elderly: A nationwide emergency department study, 1992-2000. J A m Ger, atr Soc. 2 0 0 4 ; 5 2 : 1 8 4 7 - 1 8 5 5 . Centers for Disease Control and Prevention (CDC). Assessing the National Electronic Injury Surveillance

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System-Cooperative Adverse Drug Event Surveillance project--six sates, United States, January 1-June 15, 2004. M M W R Morbid Mortal Wkly Rep. 2005;54: 380-383. Chang CM, LIH PY, Yang YH, et al. Potentially inappropriate drug prescribing among first-visit elderly outpauents in Talwan. Pharmacotherapy. 2004;24:848-855. Doshi JA, Shaffer T, Brlesacher BA. National estimates of medication use in nursing homes: Findings from the 1997 Medicare Current Beneficiary Survey and the 1996 Medical Expenditure Survey. J A m Ger~atr Soc. 2005;53:438443. Flalova D, Toplnkova E, Gambassi G, for the AdHOC Project Research Group. Potentially inappropriate medication use among elderly home care patients in Europe. l A M A . 2005;293:1348-1358. Field TS, Gurwltz JH, Harrold LR, et al. Strategies for detecting adverse drug events among older persons in the ambulatory setting. J A m Med Inform Assoc. 2004;11:492498. Franceschi A, Tuccori M, Bocci G, et al. Drug therapeutic failures in emergency department patients. A university hospital experience. Pharmacol Res. 2004; 49:85-91. Howard M, Dolovlch L, Kaczorowski J, et al. Prescribing of potentially inappropriate medications to elderly people. Faro Pract. 2004;21:244-247.

Lcapc LL, Bcrwlck DM. Five ycars aftcr To Err Is Human: What have wc learned? l A M A . 2005;293: 2384-2390. Lcchcvalhcr-Mlchcl N, Gautlcr-Bcrtrand M, Alpcrovltch A, ct al, for thc 3C Study Group. Frcqucncy and risk factors of potcntlally inapproprlatc mcdlcatlon usc in a communlty-dwclhng cldcrly population: Rcsults from thc 3C Study. Eur J Chn Pharmacol. 2005;60:813-819. Risk KJ, Wclls KJ, Tcltcl GS, ct al. Can an algorithm for approprlatc prcscrlblng prcdlct advcrsc drug cvcnts? A m J M a n a g Care. 2005;11:145-151. Rochon PA, Lane CJ, Bronskill SE, et al. Potentially inappropriate prescribing in Canada relative to the US. Drugs Aging. 2004;21:939-947. Simon SR, Chin I(~k, Soumerai SB, et al. Potentially inappropriate medication use by elderly persons in U.S. health maintenance organizations, 2000-2001. J A m Ger~atr Soc. 2005;53:227-232. Sloane PD, Gruber-Baldini AL, Zimmerman S, et al. Medication undertreatment in assisted living settings. Arch Intern Med. 2004;164:2031-2037. Vlswanathan H, Bharmal M, Thomas J III. Prevalence and correlates of potentially inappropriate prescribing among ambulatory older patients in the year 2001: Comparison of three explicit criteria. Chn Ther. 2005;27:88-99.

Address correspondence to: Joscph T. Hanlon, PharmD, MS, Division of Gcrlatrlc Medicine, Department of Medicine, University of Pittsburgh, Kaufman Medical Building, Suite 514, 3471 5th Avenue, Pittsburgh, PA 15213. E-mall: [email protected]

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