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In a confined versus ambulatory Medicaid population Drug Utilization and Potential Drug-Drug Interactions
In a confined versus ambulatory Medicaid population
By Marc F. Laventurier, Drug Utilization Robert B. Talley, Dennis L. Hefner and Lon H. Kennard and Potential Drug-Drug Interactions
Recently, social legislation has permitted access to "wellness " for the majority of the people in the U.S. This legislation has fostered a climate suitable to encourage discussion and analysis of various therapeutic procedures . In the early 1970s a multi professional corps of specialists began to build a body of literature, gaining an ever-widening audience for the study of adverse drug reactions and drug-drug interactions among health practitioners, administrators and soc ial planners . Modern pharmacology and clinical pharmacy texts have emphasized this research and placed most health practitioners in a favorable position to prevent some of the dangers inherent to modern drug therapy. The necessity of maintain ing accountability in the delivery of health in the burgeoning third-party programs introduced the computer as a management and research tool. It is capable of processing vast amounts of information and , if properly programmed , perm its cl inicians to quantify the magnitude of potential drug-drug interactions in a patient population . In the beginning, most drug surveillance programs were hospital based. 1- 4 The theme of the January 1975 issue of JAPhA 5 was " Pharmacist's Involvement in Long-Term Care Facilities." It featured seven articles on mon itoring of drug therapy by pharmacists specializing in nurs ing home care . In their article entitled " Frequency of Potential Drug-Drug Interactions , ,,6 Cooper, et al. reported results of drug interactions on nursing home patients. Two of the authors of this article in an earl ier article reported on the inc idence of potential drug-drug interactions in the same total population ,7 that did not differentiate between the location of the patient. The present report is the only one, to our
knowledge, that compares the incidence of potential drug-drug interactions for a large population at risk in both ambulatory and nursing home settings. The study was carried out for one year while the patients were under the care of the same practitioners. Methodology In August 1970, the San Joaquin Foundation for Medical Care subcontracted the administration of the Medi-Cal Drug Program to PAID Prescriptions on a fixed prepaid capitation basis. As part of a federal grant, PAID Prescriptions was charged with examining drug-drug interactions under a subcontract from the San Joaquin Foundation for Medical Care . Results reported in this article are derived from the federally financed project. 9 The study of ambulatory and nursing home patients was confined to the fiscal year ending July 31 , 1972. During this year, the total Medi-Cal population under study was 53,306 , which provided an average of 45 ,499 persons who were eligible for Medi-Cal coverage each month (Table I, below left) . The total population received prescriptions valued at 401 ,663 $1 ,830 ,658 and the average prescription price was $4 .56 (Table II, below) . The Medi-Cal program has a restrictive formulary which excludes some legend drugs and most o-t-c drugs (the notable exception is certain forms of o-t-c antacids). A total of 855 nursing home patients, representing 1.9 percent of the average monthly Medicaid population , was confined in 51 skilled nursing facilities for the entire study period . These patients remained in the faci lity for the entire year. Although several other patients (average daily census of 397) entered nursing homes for a short duration , or left the institution before the end of the year, the study was limited Table II
Table I
Average Study Popu lation per Month
Med i-Cal Category *
Cash Grant
Medica lly Needy
To tal
OAA ATD AB AFDC Total
8,352 5,051 372 30 ,197 43 ,972
1,082 152 16 277 1,527
9,434 5,203 388 30,474 45 ,499
*O AA-O l d Age ASS i stance; A T D-A i d To T otally Di sab led; AB- Aid t o B l in d; AFDC- Aid to F am ilies W ith D e p e ndent Children.
to the 855 patients who accounted for 68.3 percent of the 1,252 average daily SNF patient population. The data base of 401 ,663 prescriptions was examined for potential drug interactions by use of a computerized retrospective analysis . Six common, pre-screenable drug-drug interactions were selected for the study (See list, page 80) . Although APhA 's Evaluations of Drug Interactions identifies numerous potentially harmful interactions, the restricted formulary 'used in the Medi-Cal program precluded the occurrence of the other most common interactions. Injectables also were included in the study criteria but were not a significant factor because of their exclusion from the Medi-Cal nursing home formulary . In order to use an injectible in a nursing home setting, the physician must obtain a prior authorization for the product. Although a few claims for electrolytes and fluids were recorded during the survey period, none was involved in a potential interaction. Once the criteria were applied to the data, a patient profile of each potential situation was printed and examined . This was done to determine whether the patient received enough medication to justify the conclusion that the contraindicated products could have been taken simultaneously. Only contraindication situations which could be verified from the patient profiles are reported in the results. Results Of the total $1.8 million spent for prescription drugs during the survey year, $158,578 was spent on 36,441 prescriptions for the surveyed nursing home population. This means that 1.9 percent of the population accounted for 8.7 percent of the dollars and 9. 1 percent of the prescriptions .
Drug Utilization by Surveyed Medi-Cal Population (August 1, 1971-July 31,1972)
Average nu mber of eligibles per mo n th Total number of eligibles * Tota l number of prescript io ns To tal valu e of prescript ions Average number of prescriptions per eligible Average dollars per eligible Average prescription pr ice
Total Medi-Cal
Am bulatory Patients
Nursing Home Patients
45 ,499 40,552 401 ,663 $1,830 ,658
44,645 39 ,6 97 365 ,098 $1,672,107
855 855 36 ,565 $158,551
9.9 $45 .14 $4.56
9.2 $42.12 $4.58
42.8 $185.44 $4.34
* T h ese e l igi bl es were enrol l ed f o r the entire 12-mo n th st ud y per iod.
Vol. NS 16, No.2, February 1976
77
Drug Utilization and Potential Drug-Drug Interactions
Table III
Facility 1 2
3
4 5 6 7 8 9 10 11 12 13 14 15
Drug Utilization Rates and Changes For Medi-Cal Patients in Surveyed Nursing Homes (August 1971July 31(1972)
Number of Patients per Facility 79 61 53 49 47 47 46
44 35 32 31 30 28 23 22
37.15 28.75 55 .8 1 47.47 34 .02 32.91 45.48 58.07 55.49 50.34 62.52 50.90 30.39 52.48 3 1. 64
$161.5 8 128.39 243.9 4 189.41 146.91 164.17 211.41 251.43 251.69 218.84 232.26 19 1.1 3 11 7.43 227.52 145 .59
$ 189.29
$.44 .35 .67 .52 .40 .45 .58 .69 .69 .60 .63 .52 .32 .62 .40
$ 174.86
$.48
Grand Total
$185.44
$.5 1
42.76
Ambulatory Nursing Home Nursing Patients' Patients Hom e - - - -- -- -------Incidence Number Percent Number Percent Number Percent as Percent Receiving of Re ceiving of Receiving of of AmbuInterTotal InterTotal InterTo tal latory acting (Total = acting (Total = acting (Total = Inci40 ,552) Drugs 39,697) Drugs 855) den ce Drugs
Type of Interac tio n
1. Oral anticoagulant 68 int eractions 2. Antidiabetic drug 847 interactions 3. Digitalis/diure tics 1,414 without potassium 4. Guanethidin e/ 13 Tri cyclic antidepressant 5. T etracy clines and 55 1 antacids 6. Uricosuri c acids/ 90 sa licyla tes Total 2,66 1 (Duplication eliminated)
.17%
68
.17%
o
2.09
800
2.02
47
3.49
1,278
3.22
136
.03
13
.03
0
1.36
522
1.3 1
29
.22
89
.22
6.56(;!
2,47 1
6.22(k,
Z-scores' (** = sig. at .01 level)
190
5.50% 272%
7.05**
15.9 1
494
20.0 1**
3.39
259
5. 19**
. 12
55 18.70**
22 . 22'k' 35 y1"
'O nly the 855 long-term nursin g h ome patients have been excluded fr om th i s category, which means several of the "ambulatory" patients had short duration stays in nur si ng homes. Del et i o n of the se patients from the figures shou l d n ot ap preci abl y a l ter t he results . ' The fo ll owing Z -score formula was used to test the significance of the d i ffere n ces: z =
yrr(l ------
$.5 2
Total other 36 Facilities 228 39.59
Number of Persons Exposed to Potential Drug-Drug Interactions (August 1, 1971-July 31(1972) Total Medi-Cal Patients in Survey Counties
Prescriplions per Prescription Cost Patient per Patient per Daily Annual Year
Total, 15 largest facili ties 627 4 3.92
855
Table IV
P, -
P,
iT) ( ~ +~ ) nI
A comparison of the drug utilization patterns of nursing home versus ambulatory patients yields the expected results . The number of prescriptions received by patients is 465 percent greater (42 .1 versus ~.2 prescriptions per eligible per year) for nursing home patients while average dollars per recipient are 440 percent greater ($185.44 versus $42.12). A detailed breakdown of drug utilization by patients in each of the 51 nursing homes is shown in Table III (above) . The average daily cost of prescriptions was 51 cents, ranging from 32 cents to 69 cents for the 15 largest homes. Analysis of the prescriptions received by the sample population reveals a high incidence of potential drug-drug interactions occurring in nursing homes for three of the six categories (Table IV, above) . A survey of the total population of 855 confined Medi-Cal patients reveals that 136 re-
78
, whe r e n i s sa mpl e si ze , k is numb er of observat i ons, P i s kin , and 7T is ( k, + k, )1
n2
ceived digitalis and a diuretic prescription within 60 days of each other and did not immediately receive a potassium supplement. Nearly 16 percent of all surveyed persons were exposed to this potentially dangerous situation unless an adjustment was made in the patients' diets. Of the 136 persons involved in this type of interaction , 50 (37 percent) received a potassium supplement within 30 days; 13 (9 percent) received a potassium supplement after 30 days, and 73 (54 percent) received no potassium supplement (Table V, page 79) . A high incidence of potential interactions is noted in two other categories . There were 47 persons (5 .5 percent of the surveyed population) involved in antidiabetic drug interactions, and 29 persons (3 .4 percent) receiving prescriptions for tetracycline and antacids within seven days of each other . The latter interaction could have been less than the data indicat-
(n ,
+
n,).
ed if there were dosage schedule adjustments in the patients ' tetracycline-antacid regime . Only one patient received a uricosuric agent/salicylate combination, and no patients were exposed to potential interactions in the other two categories . Since the same person might have had two or more different types of potential interactions during the survey period, the total number of persons had to be adjusted to eliminate the duplication . There was a total of 213 potential interactions found in nursing homes. Of these, 168 involved persons who were exposed to only one type of interaction during the survey period . Twenty-two persons were exposed to two or more potential interactions and therefore accounted for the other 45 cases . With duplication eliminated , the total number of nursing home patients receiving interacting drugs was found to be over 22
Journal of the American Pharmaceutical Association
Laventurier, Talley, Hefner and Kennard
percent of the surveyed population. In other words, more than one out of every five Medi-Cal patients confined to a nursing home during the survey period was subjected to a potential drug-drug interaction. For a comparison, results for the ambulatory patients are shown in Tables IV and V. Overall, 6.2 percent of the ambulatory patients were exposed to potentially dangerous interactions. In the three categories where interactions were most common in nursing homes, the likelihood of a patient receiving interacting drugs ranged from two and a half to five times more for the nursing home patient than for the total population. In fact, the adjusted totals reveal that a Medi-Cal patient confined in a nursing home has a 357 percent greater chance of receiving potentially interacting drugs than does the ambulatory Medi-Cal patient. The difference in incidence of interacting drugs noted between the two populati ons was examined for significance-the results shown in Table IV could have occurred by chance less than one percent of the time. There is little doubt that prescription therapy in nursing homes exposes patients to a substantially greater number of potential drug-drug interactions than does ambulatory drug treatment.
Discussion It is surprising to find such large differences between the incidence of potential interactions in nursing home and ambulatory patients. The confined patient usually is treated by the same physician and pharmacist during his stay, which means the environment and drug therapy should be more controlled. In an outpatient situation, when patients "hop" from physician to physician and pharmacy to pharmacy, the potential for drug-drug interactions could be expected to be more frequent. The study was a retrospective examination for possible interactions, and does not purport to measure actual interactions. The interaction situation could have been avoided by discontinuing the use of one product before prescribing the contraindicated item, by making the appropriate dosage schedule adjustment or by ordering dietary adjustments. The computer analysis does not provide the information necessary to determine whether any of these possible adjustments were made. However, the fact that many of the digitalis-diuretic patients later received a potassium supplement tends to substantiate the contention that some of the potential interactions were actual interactions.
Vol. NS 16, No.2, February 1976
Table V
Number of Persons Exposed to Potential Digitalis/Diuretics Interactions (August 1, 1971-July 31, 1972) Ambulatory Patients Number
Digitalis/Diuretics Without Potassium 1) Received potassium supplement within 30 days 2) Received potassium 3) Received np potassium supplement Total
296
94 888 1,278
Nursing Home Patients
Percent of Total
Number
Percent of Total
23.2% 7.4 69.5 100.0%
50 13 73 136
36.8% 9.6 53.7 100.0%
Marc F. Laventurler
Marc F. Laventurier, BS, is senior vice president in charge of research and development, PAID Prescriptions, having joined the firm in 1970 as vice president of professional services. He served as secretary of the company 's first Drug Utilization Review Committee in the San Joaquin area and has had a vital role in the development of the peer review function in the areas where PAID administers the Title XIX drug program. Since 1970, he also has been a lecturer in the clinical pharmacy program of the University of California at San Francisco, where he earned his BS in pharmacy in 1951. For 18 years, Laventurier practiced community pharmacy in the East Bay area. He has been active in various pharmaceutical associations for many years, including APhA, ACA, FIP and the California Pharmaceutical Association .
Robert B. Talley
Robert B. Talley, MD, is chief of medicine at St. Joseph's Hospital and president of the San Joaquin Foundation for Medical Care, Stockton, California. He also has a private practice in internal medicine. He serves as a member of the Community Service Committee, American College of Physicians, and on the Advisory Committee on National Health Insurance for Ways and Means of Congress. Talley earned his MD from Colorado University school of medicine, with internship at Wayne County General Hospital, Eloise, Michigan, and residency at State University of Iowa, department of internal medicine. He is a member of AMA, California Academy of Medicine and the San Joaquin Medical Society.
Dennis L. Hefner
Dennis L. Hefner, PhD, is director of research for PAID Prescriptions and also serves as an associate professor of economics at California State University in Chico and as consultant, Health Policy Program, University of California, San Francisco. For two years Hefner was an economist/social science research analyst, Drug Studies Branch, Office of Research and Statistics, Social Security Administration, HEW. He is a member of the American Economic Association, Health Economics Research Organization and Western Economic Association .
Lon H. Kennard
LonH. Kennard, MBA, is vice president of planning and marketing services for Health Applications Systems, Burlingame, California. He is responsible for directing corporate personnel developing comprehensive, integrated research and marketing support capabilities . Formerly, Kennard was manager of health economics for Hoffmann-La Roche, Inc., where he directed the analysis, interpretation and identification of relevant trends and critical issues in health care that relate to the corporation as well as implementation of specific courses of action based on these analyses.
79
Drug Utilization and Potential Drug-Drug Interactions
Although the Cooper, et al. study6 of drug interactions in nursing homes used a slightly different methodology and examined a larger number of potentially significant interactions, comparisons with their results yields some interesting trends . The 22.22 percent incidence of drug interactions in nursing homes for six interactions is similar to the 23 .39 percent for 11 interactions in the Cooper study. Also, in the Cooper study, the three most frequent types of interactions (digitalis/ diuretics without potassium, antidiabetic drug interactions, and tetracyclines and antacids) had a frequency ranking of one, two and four. Cooper, et al. found that 46 of the 124 patients (from a 530-patient population) who were exposed to drug interactions required communications with the prescriber. If this result is applied to the current study it would mean that 71 of our 855 surveyed patients (8 .3 percent) were actually exposed to a potentially serious situation . If this percentage also applies to the ambulatory population, then 917 of the ambulatory Medi-Cal patients faced a similar situation. Similarly, Maronde, in a study financed by HEW,10 using different criteria in an outpatient population receiving medical care from the clinics at the University of Southern California/Los Angeles County Medical Center, reported the magnitude of potential drug-drug interactions was 7.5 percent. This compares favorably with the finding of 6.22 percent in the present study. Summary Of over 400,000 Medi-Cal prescriptions dispensed in fiscal year 1972, nursing home patients have considerably higher utilization rates than do ambulatory patients-42. 1 versus 9.2 prescriptions per patient per year. While differences in utilization were anticipated because of the age and poorer health of nursing home patients, the higher incidence of exposure to potential drug-drug interactions was unexpected because of the controlled patient environment. Nevertheless, over 22 per-, cent of the confined patients was exposed to at least one potential interaction situation, while only six percent of the ambulatory patients from the same population base was similarly exposed. The results tend to support conclusions of previous investigations. This study provides documentation on the need for careful monitoring of the drug therapy provided nursing home patients. In July 1975, the state of California agreed to pay six cents per Medi-Cal patient day for consulting
80
Six Common, Pre-Screenable Drug-Drug Interactions 1. Oral Anticoagulant Interactions-Includes all cases where an interacting prescription was received during the 60 days preceding and following the dispensing of an oral anticoagulant prescription . Anticoagulant Drug Versus Drug Interactor Warfarin sodium Clofibrate Bishydroxycoumarin Chloramphenicol Barbiturates and barbiturate-containing compounds Acenocoumarol Chloral hydrate, ethchlorvynol and glutethimide Ethyl biscoumacetate Indomethacin, phenylbutazone, and oxyphenbutazone Griseofulvin Quinidine compounds and quinine Tolbutamide, tolazamide and chlorpropamide Aspirin, aspirin combinations and sodium salicylate 2. Antidiabetic Drug Interactions-Includes all cases where an interacting prescription was received during the 60 days preceding and following the dispensing of an antidiabetic drug prescription . Antidiabetic Drug versus Drug Interactor Insulin Chloramphenicol Bishydroxycoumarin Chlorpropamide Tolbutamide Phenylbutazone and/or oxyphenbutazone Acetohexamide Propranolol Aspirin, aspirin combinations and sodium salicylate Tolazamide Sulfisoxazole and sulfinpyrazone 3. Digitalis-Diuretic Without Potassium-Includes all cases where digitalis and diuretic were prescribed within 60 days of each other and potassium supplement was not prescribed at that time . This category was divided into three subclasses : (1) a potassium supplement was prescribed within 30 days of the date both drugs were being used; (2) a potassium supplement was prescribed but only after the two drugs had been used simultaneously for more than 30 days; (3) no potassium supplement was prescribed . Potassium sparing diuretics (spironolactone and triamterene) were not on the Medi-Cal formulary during the survey period. Digitalis Digitalis Digitoxin Digoxin Gitalin
With Potassium Depleting Diuretics Thiazide and thiazide-containing compounds Chlorthalidone and compounds Furosemide Ethacrynic acid
versus Absence of Potassium Potassium chloride Potassium Triplex
4. Guanethidine-Tricyclic Antidepressant-Includes all cases where a tricyclic antidepressant and guanethidine were prescribed within 60 days of each other. Guanethidine versus Tricyclic Antidepressants Guanethidine Amitriptyline with perphenazine Guanethidine with hydrochlorothiazide Desipramine hydrochloride Amitriptyline Nortriptyline Imipramine 5. Tetracycline-Antacids-Includes all cases where tetracycline and antacids which have divalent or trivalent cations were prescribed within seven days of each other. Tetracycline versus Antacid Preparation Tetracycline Antacids containing calcium, magnesium and/or aluminum salts 6. Uricosuric Agents-Salicylates-Includes all cases where uricosuric agents and sal icylates were prescribed within 60 days of each other. Uricosurics versus Salicylates Probenecid Codeine and aspirin combinations Probenecid with colchicine Propoxyphene HCI and aspirin combinations Sulfinpyrazone Oxycodone salts (HCI and terephthate) plus APC Sodium salicylate
Journal of the American Pharmaceutic al Association
Laventurier, Talley, Hefner and Kennard
pharmacy services in a nursing home setting. While it is too early to determine the impact of the new program, it is hoped that adoption of this economic incentive will reduce the problems identified in the study.
•
References 1. Seidl, L. G., Thornton, G. F., Smith, J. W., et al., "Studies on the Epidemiology of Adverse Drug Reactions III, Re-
For the Bicentennial
AIHP Issues Aids for Pharmacy Participation; Dedicates Historical Marker The American Institute of the History of Pharmacy is making available a variety of historical materials that can be utilized by pharmacists to help observe the country's Bicentennial, AIHP Director John Parascandola announces . Cooperating members and agencies have helped the Institute put together a unique "Bicentennial Packet." This contains a balanced selection of nine different resources relating pharmacy to life and medical care in early America. There is a slide-talk, a portfolio of six photographs, facsimiles of the Lititz and Coste formularies, two comprehensive bibliographic keys to relevant literature, two narrative booklets, and the Bicentennial issue of Pharmacy Times. The postpaid price of the Bicentennial packet is $26 to nonmembers ($19 to members). A price list of additional Bicentennial material may be obtained on request to the American Institute of the History of Pharmacy Pharmacy Building., Madison, WI 53706. Orders also are being received for an AIHP Display Kit, available February 1,
Captain Petoletti Receives Andrew Craigie Award Captain Angelo R. Petoletti, MSC, of the United States Navy, was presented the 1975 Andrew Craigie Award on December 11 during the 82nd annual meeting of the
Vol. NS 16, No. 2, February 1976.
2. 3. 4.
5. 6.
actions in Patients on a General Medical Survey, " . Bull. Johns Hopkins Hosp., 119, 229-315 (1966) Schimmel, E. M., "The Hazards of Hospitalization," "Ann. Intern. Med., 60,1001-1006 (1967) Hurwitz, N., "Admissions to Hospital Due to Drugs," Brit. Med. J., 1,536 (1969) Gardner, P., and Cluff, L. E., "The Epidemiology of Adverse Drug Reactions- A Review and Perspective," The Johns Hopkins Med. J., 126, 77-87 (1970) JAPhA, NS15, (1) (1975) Cooper, J. W ., Wellins, I. , Fish , K. H., and Loomis, M. E., "Frequency of Potential Drug-Drug Interactions," JA PhA , NS15, (1), 24 (1975)
1976. This separate unit is designed to simplify installation of small exhibits by pharmacists, with the aid of pieces of antique pharmaceutical equipment available locally. The nine display cards in the kit may be used in various combinations, according to suggestions in ao accompanying brochure. The display kit ($10 to non-members; $5 to AIHP members) will remain available throughout the bicentennial period, beginning in February. The American Institute of the History of Pharmacy also is planning a Bicentennial symposium associated with the APhA Annual Meeting in April, Dr. Parascandola announced.
Marker Dedicated One of pharmacy's contributions to the Bicentennial observance culminated at the dedication of an historical marker in Carlisle, Pennsylvania, on Saturday, January 24, 1976, under jOint sponsorship by the American Institute of the History of Pharmacy and the Pennsylvania Pharmaceutical Association. Cooperating with the AIHP and the PPhA were the Army War College, the U.S. Army Military History Research Collection, and Carlisle Barracks, which comprise the installations at the post. Carlisle Barracks has played a part in the military history of the country since its
Association of Military Surgeons of the United States. A silver plaque and honorarium, awarded by the Association of Military Surgeons and sponsored by Lederle Laboratories Division of Cyanamid Company, were presented to Captain Petoletti for his "outstanding contributions in the advancement of professional pharmacy in the federal government. " Captain Petoletti is chief of Pharmacy Service at the Naval Regional Medical Center in Oakland, California. He also has served on the staff of the Naval Hospital in Guam and the Defense Personnel Support Center when it was located in Brooklyn,
7. Talley, R. B., and Laventurier, M. F., "The Incidence of Drug-Drug Interactions," Calif. Pharm. , XX (5), 18-22 (1975) 8 . Laventurier, M. F., "Guidelines of Drug Utilization of the San Joaquin Pharmaceutical Society," Calif. Pharm., 18 (8),8-15 (1971) 9. HEW; Analysis of Medical Care Data (San Joaquin), Contract # HSMHA-HSM-11 0-7,1-204 10. Department of Health, Education and Welfare, Social Security Administration, "Drug Utilization Review with OnLine Computer Capabilities: Selected Methodology and Findings from a Demonstration," 73-11853 , Staff Paper #13
founding; and there occurred one of the significant events in the history of pharmacy during the Revolution. Therefore the Council of the American Institute of the History of Pharmacy selected the site for a bronze marker, which readsApothecary-General Andrew Craigie established at Carlisle, by 1778, a manufacturing pharmacy and 'issuing store' where medicines were prepared and medicine chests were assembled and replenished for the hospitals of the Revolutionary Forces. From here the art of the apothecary went forth to contribute to the cause of liberty. The marker was accepted on behalf of the United States Army by the commandant of the post~ after unveiling ceremonies conducted by officers of the Pennsylvania Pharmaceutical Association and the American Institute of the History of Pharmacy. This will be the seventh in a series of bronze markers being set by the Institute periodically on sites selected and authenticated as the scene of some pharmaceutical events having national significance. Because of the Bicentennial occasion the AIHP has authorized two additional markers to be dedicated later in 1976 at Lititz and Philadelphia, Pennsylvania.
New York as the Military Medical Agency. In other Navy assignments, he has been chief, Training Division of the Hospital Corps School at Great Lakes, Illinois; chief, Pharmacy Service at the Naval Dispensary in Washington, D.C. and the Naval Hospital in St. Albans, New York. Captain Petoletti has served as chairman of the APhA Section on Federal Pharmacy, and is an active member of the American Society of Hospital Pharmacists and the Association of Military Surgeons. He works as a volunteer in drug abuse education, alcoholism prevention and other general health community programs in the Oakland, California area.
81
By Marc F. Laventurier, Drug Utilization Robert B. Talley, Dennis L. Hefner and Lon H. Kennard and Potential Drug-Drug Interactions
Recently, social legislation has permitted access to "wellness " for the majority of the people in the U.S. This legislation has fostered a climate suitable to encourage discussion and analysis of various therapeutic procedures . In the early 1970s a multi professional corps of specialists began to build a body of literature, gaining an ever-widening audience for the study of adverse drug reactions and drug-drug interactions among health practitioners, administrators and soc ial planners . Modern pharmacology and clinical pharmacy texts have emphasized this research and placed most health practitioners in a favorable position to prevent some of the dangers inherent to modern drug therapy. The necessity of maintain ing accountability in the delivery of health in the burgeoning third-party programs introduced the computer as a management and research tool. It is capable of processing vast amounts of information and , if properly programmed , perm its cl inicians to quantify the magnitude of potential drug-drug interactions in a patient population . In the beginning, most drug surveillance programs were hospital based. 1- 4 The theme of the January 1975 issue of JAPhA 5 was " Pharmacist's Involvement in Long-Term Care Facilities." It featured seven articles on mon itoring of drug therapy by pharmacists specializing in nurs ing home care . In their article entitled " Frequency of Potential Drug-Drug Interactions , ,,6 Cooper, et al. reported results of drug interactions on nursing home patients. Two of the authors of this article in an earl ier article reported on the inc idence of potential drug-drug interactions in the same total population ,7 that did not differentiate between the location of the patient. The present report is the only one, to our
knowledge, that compares the incidence of potential drug-drug interactions for a large population at risk in both ambulatory and nursing home settings. The study was carried out for one year while the patients were under the care of the same practitioners. Methodology In August 1970, the San Joaquin Foundation for Medical Care subcontracted the administration of the Medi-Cal Drug Program to PAID Prescriptions on a fixed prepaid capitation basis. As part of a federal grant, PAID Prescriptions was charged with examining drug-drug interactions under a subcontract from the San Joaquin Foundation for Medical Care . Results reported in this article are derived from the federally financed project. 9 The study of ambulatory and nursing home patients was confined to the fiscal year ending July 31 , 1972. During this year, the total Medi-Cal population under study was 53,306 , which provided an average of 45 ,499 persons who were eligible for Medi-Cal coverage each month (Table I, below left) . The total population received prescriptions valued at 401 ,663 $1 ,830 ,658 and the average prescription price was $4 .56 (Table II, below) . The Medi-Cal program has a restrictive formulary which excludes some legend drugs and most o-t-c drugs (the notable exception is certain forms of o-t-c antacids). A total of 855 nursing home patients, representing 1.9 percent of the average monthly Medicaid population , was confined in 51 skilled nursing facilities for the entire study period . These patients remained in the faci lity for the entire year. Although several other patients (average daily census of 397) entered nursing homes for a short duration , or left the institution before the end of the year, the study was limited Table II
Table I
Average Study Popu lation per Month
Med i-Cal Category *
Cash Grant
Medica lly Needy
To tal
OAA ATD AB AFDC Total
8,352 5,051 372 30 ,197 43 ,972
1,082 152 16 277 1,527
9,434 5,203 388 30,474 45 ,499
*O AA-O l d Age ASS i stance; A T D-A i d To T otally Di sab led; AB- Aid t o B l in d; AFDC- Aid to F am ilies W ith D e p e ndent Children.
to the 855 patients who accounted for 68.3 percent of the 1,252 average daily SNF patient population. The data base of 401 ,663 prescriptions was examined for potential drug interactions by use of a computerized retrospective analysis . Six common, pre-screenable drug-drug interactions were selected for the study (See list, page 80) . Although APhA 's Evaluations of Drug Interactions identifies numerous potentially harmful interactions, the restricted formulary 'used in the Medi-Cal program precluded the occurrence of the other most common interactions. Injectables also were included in the study criteria but were not a significant factor because of their exclusion from the Medi-Cal nursing home formulary . In order to use an injectible in a nursing home setting, the physician must obtain a prior authorization for the product. Although a few claims for electrolytes and fluids were recorded during the survey period, none was involved in a potential interaction. Once the criteria were applied to the data, a patient profile of each potential situation was printed and examined . This was done to determine whether the patient received enough medication to justify the conclusion that the contraindicated products could have been taken simultaneously. Only contraindication situations which could be verified from the patient profiles are reported in the results. Results Of the total $1.8 million spent for prescription drugs during the survey year, $158,578 was spent on 36,441 prescriptions for the surveyed nursing home population. This means that 1.9 percent of the population accounted for 8.7 percent of the dollars and 9. 1 percent of the prescriptions .
Drug Utilization by Surveyed Medi-Cal Population (August 1, 1971-July 31,1972)
Average nu mber of eligibles per mo n th Total number of eligibles * Tota l number of prescript io ns To tal valu e of prescript ions Average number of prescriptions per eligible Average dollars per eligible Average prescription pr ice
Total Medi-Cal
Am bulatory Patients
Nursing Home Patients
45 ,499 40,552 401 ,663 $1,830 ,658
44,645 39 ,6 97 365 ,098 $1,672,107
855 855 36 ,565 $158,551
9.9 $45 .14 $4.56
9.2 $42.12 $4.58
42.8 $185.44 $4.34
* T h ese e l igi bl es were enrol l ed f o r the entire 12-mo n th st ud y per iod.
Vol. NS 16, No.2, February 1976
77
Drug Utilization and Potential Drug-Drug Interactions
Table III
Facility 1 2
3
4 5 6 7 8 9 10 11 12 13 14 15
Drug Utilization Rates and Changes For Medi-Cal Patients in Surveyed Nursing Homes (August 1971July 31(1972)
Number of Patients per Facility 79 61 53 49 47 47 46
44 35 32 31 30 28 23 22
37.15 28.75 55 .8 1 47.47 34 .02 32.91 45.48 58.07 55.49 50.34 62.52 50.90 30.39 52.48 3 1. 64
$161.5 8 128.39 243.9 4 189.41 146.91 164.17 211.41 251.43 251.69 218.84 232.26 19 1.1 3 11 7.43 227.52 145 .59
$ 189.29
$.44 .35 .67 .52 .40 .45 .58 .69 .69 .60 .63 .52 .32 .62 .40
$ 174.86
$.48
Grand Total
$185.44
$.5 1
42.76
Ambulatory Nursing Home Nursing Patients' Patients Hom e - - - -- -- -------Incidence Number Percent Number Percent Number Percent as Percent Receiving of Re ceiving of Receiving of of AmbuInterTotal InterTotal InterTo tal latory acting (Total = acting (Total = acting (Total = Inci40 ,552) Drugs 39,697) Drugs 855) den ce Drugs
Type of Interac tio n
1. Oral anticoagulant 68 int eractions 2. Antidiabetic drug 847 interactions 3. Digitalis/diure tics 1,414 without potassium 4. Guanethidin e/ 13 Tri cyclic antidepressant 5. T etracy clines and 55 1 antacids 6. Uricosuri c acids/ 90 sa licyla tes Total 2,66 1 (Duplication eliminated)
.17%
68
.17%
o
2.09
800
2.02
47
3.49
1,278
3.22
136
.03
13
.03
0
1.36
522
1.3 1
29
.22
89
.22
6.56(;!
2,47 1
6.22(k,
Z-scores' (** = sig. at .01 level)
190
5.50% 272%
7.05**
15.9 1
494
20.0 1**
3.39
259
5. 19**
. 12
55 18.70**
22 . 22'k' 35 y1"
'O nly the 855 long-term nursin g h ome patients have been excluded fr om th i s category, which means several of the "ambulatory" patients had short duration stays in nur si ng homes. Del et i o n of the se patients from the figures shou l d n ot ap preci abl y a l ter t he results . ' The fo ll owing Z -score formula was used to test the significance of the d i ffere n ces: z =
yrr(l ------
$.5 2
Total other 36 Facilities 228 39.59
Number of Persons Exposed to Potential Drug-Drug Interactions (August 1, 1971-July 31(1972) Total Medi-Cal Patients in Survey Counties
Prescriplions per Prescription Cost Patient per Patient per Daily Annual Year
Total, 15 largest facili ties 627 4 3.92
855
Table IV
P, -
P,
iT) ( ~ +~ ) nI
A comparison of the drug utilization patterns of nursing home versus ambulatory patients yields the expected results . The number of prescriptions received by patients is 465 percent greater (42 .1 versus ~.2 prescriptions per eligible per year) for nursing home patients while average dollars per recipient are 440 percent greater ($185.44 versus $42.12). A detailed breakdown of drug utilization by patients in each of the 51 nursing homes is shown in Table III (above) . The average daily cost of prescriptions was 51 cents, ranging from 32 cents to 69 cents for the 15 largest homes. Analysis of the prescriptions received by the sample population reveals a high incidence of potential drug-drug interactions occurring in nursing homes for three of the six categories (Table IV, above) . A survey of the total population of 855 confined Medi-Cal patients reveals that 136 re-
78
, whe r e n i s sa mpl e si ze , k is numb er of observat i ons, P i s kin , and 7T is ( k, + k, )1
n2
ceived digitalis and a diuretic prescription within 60 days of each other and did not immediately receive a potassium supplement. Nearly 16 percent of all surveyed persons were exposed to this potentially dangerous situation unless an adjustment was made in the patients' diets. Of the 136 persons involved in this type of interaction , 50 (37 percent) received a potassium supplement within 30 days; 13 (9 percent) received a potassium supplement after 30 days, and 73 (54 percent) received no potassium supplement (Table V, page 79) . A high incidence of potential interactions is noted in two other categories . There were 47 persons (5 .5 percent of the surveyed population) involved in antidiabetic drug interactions, and 29 persons (3 .4 percent) receiving prescriptions for tetracycline and antacids within seven days of each other . The latter interaction could have been less than the data indicat-
(n ,
+
n,).
ed if there were dosage schedule adjustments in the patients ' tetracycline-antacid regime . Only one patient received a uricosuric agent/salicylate combination, and no patients were exposed to potential interactions in the other two categories . Since the same person might have had two or more different types of potential interactions during the survey period, the total number of persons had to be adjusted to eliminate the duplication . There was a total of 213 potential interactions found in nursing homes. Of these, 168 involved persons who were exposed to only one type of interaction during the survey period . Twenty-two persons were exposed to two or more potential interactions and therefore accounted for the other 45 cases . With duplication eliminated , the total number of nursing home patients receiving interacting drugs was found to be over 22
Journal of the American Pharmaceutical Association
Laventurier, Talley, Hefner and Kennard
percent of the surveyed population. In other words, more than one out of every five Medi-Cal patients confined to a nursing home during the survey period was subjected to a potential drug-drug interaction. For a comparison, results for the ambulatory patients are shown in Tables IV and V. Overall, 6.2 percent of the ambulatory patients were exposed to potentially dangerous interactions. In the three categories where interactions were most common in nursing homes, the likelihood of a patient receiving interacting drugs ranged from two and a half to five times more for the nursing home patient than for the total population. In fact, the adjusted totals reveal that a Medi-Cal patient confined in a nursing home has a 357 percent greater chance of receiving potentially interacting drugs than does the ambulatory Medi-Cal patient. The difference in incidence of interacting drugs noted between the two populati ons was examined for significance-the results shown in Table IV could have occurred by chance less than one percent of the time. There is little doubt that prescription therapy in nursing homes exposes patients to a substantially greater number of potential drug-drug interactions than does ambulatory drug treatment.
Discussion It is surprising to find such large differences between the incidence of potential interactions in nursing home and ambulatory patients. The confined patient usually is treated by the same physician and pharmacist during his stay, which means the environment and drug therapy should be more controlled. In an outpatient situation, when patients "hop" from physician to physician and pharmacy to pharmacy, the potential for drug-drug interactions could be expected to be more frequent. The study was a retrospective examination for possible interactions, and does not purport to measure actual interactions. The interaction situation could have been avoided by discontinuing the use of one product before prescribing the contraindicated item, by making the appropriate dosage schedule adjustment or by ordering dietary adjustments. The computer analysis does not provide the information necessary to determine whether any of these possible adjustments were made. However, the fact that many of the digitalis-diuretic patients later received a potassium supplement tends to substantiate the contention that some of the potential interactions were actual interactions.
Vol. NS 16, No.2, February 1976
Table V
Number of Persons Exposed to Potential Digitalis/Diuretics Interactions (August 1, 1971-July 31, 1972) Ambulatory Patients Number
Digitalis/Diuretics Without Potassium 1) Received potassium supplement within 30 days 2) Received potassium 3) Received np potassium supplement Total
296
94 888 1,278
Nursing Home Patients
Percent of Total
Number
Percent of Total
23.2% 7.4 69.5 100.0%
50 13 73 136
36.8% 9.6 53.7 100.0%
Marc F. Laventurler
Marc F. Laventurier, BS, is senior vice president in charge of research and development, PAID Prescriptions, having joined the firm in 1970 as vice president of professional services. He served as secretary of the company 's first Drug Utilization Review Committee in the San Joaquin area and has had a vital role in the development of the peer review function in the areas where PAID administers the Title XIX drug program. Since 1970, he also has been a lecturer in the clinical pharmacy program of the University of California at San Francisco, where he earned his BS in pharmacy in 1951. For 18 years, Laventurier practiced community pharmacy in the East Bay area. He has been active in various pharmaceutical associations for many years, including APhA, ACA, FIP and the California Pharmaceutical Association .
Robert B. Talley
Robert B. Talley, MD, is chief of medicine at St. Joseph's Hospital and president of the San Joaquin Foundation for Medical Care, Stockton, California. He also has a private practice in internal medicine. He serves as a member of the Community Service Committee, American College of Physicians, and on the Advisory Committee on National Health Insurance for Ways and Means of Congress. Talley earned his MD from Colorado University school of medicine, with internship at Wayne County General Hospital, Eloise, Michigan, and residency at State University of Iowa, department of internal medicine. He is a member of AMA, California Academy of Medicine and the San Joaquin Medical Society.
Dennis L. Hefner
Dennis L. Hefner, PhD, is director of research for PAID Prescriptions and also serves as an associate professor of economics at California State University in Chico and as consultant, Health Policy Program, University of California, San Francisco. For two years Hefner was an economist/social science research analyst, Drug Studies Branch, Office of Research and Statistics, Social Security Administration, HEW. He is a member of the American Economic Association, Health Economics Research Organization and Western Economic Association .
Lon H. Kennard
LonH. Kennard, MBA, is vice president of planning and marketing services for Health Applications Systems, Burlingame, California. He is responsible for directing corporate personnel developing comprehensive, integrated research and marketing support capabilities . Formerly, Kennard was manager of health economics for Hoffmann-La Roche, Inc., where he directed the analysis, interpretation and identification of relevant trends and critical issues in health care that relate to the corporation as well as implementation of specific courses of action based on these analyses.
79
Drug Utilization and Potential Drug-Drug Interactions
Although the Cooper, et al. study6 of drug interactions in nursing homes used a slightly different methodology and examined a larger number of potentially significant interactions, comparisons with their results yields some interesting trends . The 22.22 percent incidence of drug interactions in nursing homes for six interactions is similar to the 23 .39 percent for 11 interactions in the Cooper study. Also, in the Cooper study, the three most frequent types of interactions (digitalis/ diuretics without potassium, antidiabetic drug interactions, and tetracyclines and antacids) had a frequency ranking of one, two and four. Cooper, et al. found that 46 of the 124 patients (from a 530-patient population) who were exposed to drug interactions required communications with the prescriber. If this result is applied to the current study it would mean that 71 of our 855 surveyed patients (8 .3 percent) were actually exposed to a potentially serious situation . If this percentage also applies to the ambulatory population, then 917 of the ambulatory Medi-Cal patients faced a similar situation. Similarly, Maronde, in a study financed by HEW,10 using different criteria in an outpatient population receiving medical care from the clinics at the University of Southern California/Los Angeles County Medical Center, reported the magnitude of potential drug-drug interactions was 7.5 percent. This compares favorably with the finding of 6.22 percent in the present study. Summary Of over 400,000 Medi-Cal prescriptions dispensed in fiscal year 1972, nursing home patients have considerably higher utilization rates than do ambulatory patients-42. 1 versus 9.2 prescriptions per patient per year. While differences in utilization were anticipated because of the age and poorer health of nursing home patients, the higher incidence of exposure to potential drug-drug interactions was unexpected because of the controlled patient environment. Nevertheless, over 22 per-, cent of the confined patients was exposed to at least one potential interaction situation, while only six percent of the ambulatory patients from the same population base was similarly exposed. The results tend to support conclusions of previous investigations. This study provides documentation on the need for careful monitoring of the drug therapy provided nursing home patients. In July 1975, the state of California agreed to pay six cents per Medi-Cal patient day for consulting
80
Six Common, Pre-Screenable Drug-Drug Interactions 1. Oral Anticoagulant Interactions-Includes all cases where an interacting prescription was received during the 60 days preceding and following the dispensing of an oral anticoagulant prescription . Anticoagulant Drug Versus Drug Interactor Warfarin sodium Clofibrate Bishydroxycoumarin Chloramphenicol Barbiturates and barbiturate-containing compounds Acenocoumarol Chloral hydrate, ethchlorvynol and glutethimide Ethyl biscoumacetate Indomethacin, phenylbutazone, and oxyphenbutazone Griseofulvin Quinidine compounds and quinine Tolbutamide, tolazamide and chlorpropamide Aspirin, aspirin combinations and sodium salicylate 2. Antidiabetic Drug Interactions-Includes all cases where an interacting prescription was received during the 60 days preceding and following the dispensing of an antidiabetic drug prescription . Antidiabetic Drug versus Drug Interactor Insulin Chloramphenicol Bishydroxycoumarin Chlorpropamide Tolbutamide Phenylbutazone and/or oxyphenbutazone Acetohexamide Propranolol Aspirin, aspirin combinations and sodium salicylate Tolazamide Sulfisoxazole and sulfinpyrazone 3. Digitalis-Diuretic Without Potassium-Includes all cases where digitalis and diuretic were prescribed within 60 days of each other and potassium supplement was not prescribed at that time . This category was divided into three subclasses : (1) a potassium supplement was prescribed within 30 days of the date both drugs were being used; (2) a potassium supplement was prescribed but only after the two drugs had been used simultaneously for more than 30 days; (3) no potassium supplement was prescribed . Potassium sparing diuretics (spironolactone and triamterene) were not on the Medi-Cal formulary during the survey period. Digitalis Digitalis Digitoxin Digoxin Gitalin
With Potassium Depleting Diuretics Thiazide and thiazide-containing compounds Chlorthalidone and compounds Furosemide Ethacrynic acid
versus Absence of Potassium Potassium chloride Potassium Triplex
4. Guanethidine-Tricyclic Antidepressant-Includes all cases where a tricyclic antidepressant and guanethidine were prescribed within 60 days of each other. Guanethidine versus Tricyclic Antidepressants Guanethidine Amitriptyline with perphenazine Guanethidine with hydrochlorothiazide Desipramine hydrochloride Amitriptyline Nortriptyline Imipramine 5. Tetracycline-Antacids-Includes all cases where tetracycline and antacids which have divalent or trivalent cations were prescribed within seven days of each other. Tetracycline versus Antacid Preparation Tetracycline Antacids containing calcium, magnesium and/or aluminum salts 6. Uricosuric Agents-Salicylates-Includes all cases where uricosuric agents and sal icylates were prescribed within 60 days of each other. Uricosurics versus Salicylates Probenecid Codeine and aspirin combinations Probenecid with colchicine Propoxyphene HCI and aspirin combinations Sulfinpyrazone Oxycodone salts (HCI and terephthate) plus APC Sodium salicylate
Journal of the American Pharmaceutic al Association
Laventurier, Talley, Hefner and Kennard
pharmacy services in a nursing home setting. While it is too early to determine the impact of the new program, it is hoped that adoption of this economic incentive will reduce the problems identified in the study.
•
References 1. Seidl, L. G., Thornton, G. F., Smith, J. W., et al., "Studies on the Epidemiology of Adverse Drug Reactions III, Re-
For the Bicentennial
AIHP Issues Aids for Pharmacy Participation; Dedicates Historical Marker The American Institute of the History of Pharmacy is making available a variety of historical materials that can be utilized by pharmacists to help observe the country's Bicentennial, AIHP Director John Parascandola announces . Cooperating members and agencies have helped the Institute put together a unique "Bicentennial Packet." This contains a balanced selection of nine different resources relating pharmacy to life and medical care in early America. There is a slide-talk, a portfolio of six photographs, facsimiles of the Lititz and Coste formularies, two comprehensive bibliographic keys to relevant literature, two narrative booklets, and the Bicentennial issue of Pharmacy Times. The postpaid price of the Bicentennial packet is $26 to nonmembers ($19 to members). A price list of additional Bicentennial material may be obtained on request to the American Institute of the History of Pharmacy Pharmacy Building., Madison, WI 53706. Orders also are being received for an AIHP Display Kit, available February 1,
Captain Petoletti Receives Andrew Craigie Award Captain Angelo R. Petoletti, MSC, of the United States Navy, was presented the 1975 Andrew Craigie Award on December 11 during the 82nd annual meeting of the
Vol. NS 16, No. 2, February 1976.
2. 3. 4.
5. 6.
actions in Patients on a General Medical Survey, " . Bull. Johns Hopkins Hosp., 119, 229-315 (1966) Schimmel, E. M., "The Hazards of Hospitalization," "Ann. Intern. Med., 60,1001-1006 (1967) Hurwitz, N., "Admissions to Hospital Due to Drugs," Brit. Med. J., 1,536 (1969) Gardner, P., and Cluff, L. E., "The Epidemiology of Adverse Drug Reactions- A Review and Perspective," The Johns Hopkins Med. J., 126, 77-87 (1970) JAPhA, NS15, (1) (1975) Cooper, J. W ., Wellins, I. , Fish , K. H., and Loomis, M. E., "Frequency of Potential Drug-Drug Interactions," JA PhA , NS15, (1), 24 (1975)
1976. This separate unit is designed to simplify installation of small exhibits by pharmacists, with the aid of pieces of antique pharmaceutical equipment available locally. The nine display cards in the kit may be used in various combinations, according to suggestions in ao accompanying brochure. The display kit ($10 to non-members; $5 to AIHP members) will remain available throughout the bicentennial period, beginning in February. The American Institute of the History of Pharmacy also is planning a Bicentennial symposium associated with the APhA Annual Meeting in April, Dr. Parascandola announced.
Marker Dedicated One of pharmacy's contributions to the Bicentennial observance culminated at the dedication of an historical marker in Carlisle, Pennsylvania, on Saturday, January 24, 1976, under jOint sponsorship by the American Institute of the History of Pharmacy and the Pennsylvania Pharmaceutical Association. Cooperating with the AIHP and the PPhA were the Army War College, the U.S. Army Military History Research Collection, and Carlisle Barracks, which comprise the installations at the post. Carlisle Barracks has played a part in the military history of the country since its
Association of Military Surgeons of the United States. A silver plaque and honorarium, awarded by the Association of Military Surgeons and sponsored by Lederle Laboratories Division of Cyanamid Company, were presented to Captain Petoletti for his "outstanding contributions in the advancement of professional pharmacy in the federal government. " Captain Petoletti is chief of Pharmacy Service at the Naval Regional Medical Center in Oakland, California. He also has served on the staff of the Naval Hospital in Guam and the Defense Personnel Support Center when it was located in Brooklyn,
7. Talley, R. B., and Laventurier, M. F., "The Incidence of Drug-Drug Interactions," Calif. Pharm. , XX (5), 18-22 (1975) 8 . Laventurier, M. F., "Guidelines of Drug Utilization of the San Joaquin Pharmaceutical Society," Calif. Pharm., 18 (8),8-15 (1971) 9. HEW; Analysis of Medical Care Data (San Joaquin), Contract # HSMHA-HSM-11 0-7,1-204 10. Department of Health, Education and Welfare, Social Security Administration, "Drug Utilization Review with OnLine Computer Capabilities: Selected Methodology and Findings from a Demonstration," 73-11853 , Staff Paper #13
founding; and there occurred one of the significant events in the history of pharmacy during the Revolution. Therefore the Council of the American Institute of the History of Pharmacy selected the site for a bronze marker, which readsApothecary-General Andrew Craigie established at Carlisle, by 1778, a manufacturing pharmacy and 'issuing store' where medicines were prepared and medicine chests were assembled and replenished for the hospitals of the Revolutionary Forces. From here the art of the apothecary went forth to contribute to the cause of liberty. The marker was accepted on behalf of the United States Army by the commandant of the post~ after unveiling ceremonies conducted by officers of the Pennsylvania Pharmaceutical Association and the American Institute of the History of Pharmacy. This will be the seventh in a series of bronze markers being set by the Institute periodically on sites selected and authenticated as the scene of some pharmaceutical events having national significance. Because of the Bicentennial occasion the AIHP has authorized two additional markers to be dedicated later in 1976 at Lititz and Philadelphia, Pennsylvania.
New York as the Military Medical Agency. In other Navy assignments, he has been chief, Training Division of the Hospital Corps School at Great Lakes, Illinois; chief, Pharmacy Service at the Naval Dispensary in Washington, D.C. and the Naval Hospital in St. Albans, New York. Captain Petoletti has served as chairman of the APhA Section on Federal Pharmacy, and is an active member of the American Society of Hospital Pharmacists and the Association of Military Surgeons. He works as a volunteer in drug abuse education, alcoholism prevention and other general health community programs in the Oakland, California area.
81