close

Вход

Забыли?

вход по аккаунту

?

Utilization of nonsteroidal antiinflammatory drugs.

код для вставкиСкачать
686
-_
-_
UTILIZATION OF NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
CARLENE BAUM, DIANNE L. KENNEDY, and MARY B. FORBES
Information derived from pharmaceutical marketing databases on the use of 12 nonsteroidal antiinflammatory drugs in 1983 is presented. Estimates of
population exposure, regularity of treatment, average
daily dose, age and sex distributions of users, concomitant use of other drugs, associated diagnoses, and trends
in use are provided. Utilization patterns were similar for
8 of the nonsteroidal antiinflammatory drugs, with
differing patterns seen for mefenamic acid, oxyphenbutazone, phenylbutazone, and zomepirac.
Nonsteroidal antiinflammatory drugs (NSAIDs)
are among the most frequently used drugs in the
United States. Five of the 50 drug products most often
dispensed during 1983 were NSAIDs: Motrin (#9),
Naprosyn (#20), Feldene (#27), Indocin (#28), and
Clinoril (#41). Approximately 66.5 million prescriptions for nonsalicylate NSAIDs were dispensed by
retail pharmacies in 1983, representing over 4% of the
total prescription market. Consumers spent over one
billion dollars for these prescriptions.
The opinions expressed in this paper are those of the
authors and not necessarily those of the Food and Drug Administration. The authors assume responsibility for the accurate transcription of all data and the mathematical calculations performed by the
Drug Use Analysis Branch.
From the Drug Use Analysis Branch and the Adverse
Reactions and Poisoning Surveillance Branch, Division of Drug and
Biological Product Experience, Center for Drugs and Biologics,
Food and Drug Administration, Rockville, Maryland.
Carlene Baum, PhD: Technical Information Specialist,
Drug Use Analysis Branch; Dianne L. Kennedy, RPh, MPH: Chief,
Drug Use Analysis Branch; Mary B. Forbes, RPh: Pharmacist,
Adverse Reactions and Poisoning Surveillance Branch.
Address reprint requests to Carlene Baum, PhD, Drug Use
Analysis Branch, HFN-737, FDA, 5600 Fishers Lane, Rockville,
MD 20857.
Submitted for publication May 25, 1984; accepted in revised
form December 14, 1984.
Arthritis and Rheumatism, Vol. 28, No. 6 (June 1985)
This article provides an overview of the utilization of nonsteroidal antiinflammatory drugs, including
a review of trends in the total number of NSAID
prescriptions from 1973 to 1983 and more detailed
prescription data for 1983. Information on how the
drugs are being used, as well as how much they are
used is also provided. Only nonsalicylate prescription
drugs are discussed (e.g., aspirin is not included), and
with the exception of population exposure estimates,
data reflect only outpatient use. Benoxaprofen is not
covered in this review since it was withdrawn from the
market shortly after its introduction in 1982. Zomepirac was withdrawn the following year, but is included since it was on the market for 3 years and represented a major drug exposure during that time.
METHODS
Data were drawn from 3 subscription databases
purchased by the Food and Drug Administration from IMS
America, Ltd. (1-3). The National Prescription Audit (NPA)
(1) provides information on prescriptions dispensed by chain
and independent pharmacies in the continental United
States; other outlets such as discount stores and supermarkets with pharmacies are not included. Since 1981, IMS has
received monthly data tapes on approximately 4.3 million
prescriptions dispensed by a panel of 1,200 computerized
pharmacies. Because data collection is dependent upon
computerized pharmacies, the panel does not represent a
true random sample; however, IMS does ensure that the
panel is representative of US pharmacies in terms of geographic region, type of ownership, and pharmacy size. Prior
to 1981, data were obtained from a representative sample of
800 pharmacies, each of which was audited for 2 days per
month. Therefore, changes from 1980-1981 in the number of
prescriptions reported by the NPA may reflect methodologic
revisions, as well as actual changes in drug use. The NPA
provided data for the current study on the number of
prescriptions, the percentage that were new prescriptions,
UTKLIZATION OF NSAIDs
average prescription size, and average daily dose prescribed
by physicians.
The US Pharmaceutical Market-Drugstore and
Hospital Purchases (2) provides national estimates of pharmaceutical purchases based on invoices from a drugstore
panel of 840 retail outlets and 439 warehouses and a hospital
panel of 350 hospitals and 362 wholesalers. It covers a
broader range of drugstore outlets than the National Prescription Audit and represents hospital use as well, but
contains more limited summary figures. Dollar costs are
summarized for products and classes, but information on
drug quantity is presented only for the individual strengths
and package sizes of each manufacturer (e.g., 565,000 bottles containing 500 tablets of Upjohn’s 600-mg ibuprofen).
Data on individual drug quantity were used to calculate the
total kilograms of each NSAID purchased by drugstores and
hospitals in 1983. The kilogram data were then used to
estimate population exposure through a method based on the
concept of the defined daily dose (DDD) developed and
routinely used by European drug researchers (4). A DDD for
a particular drug represents the average maintenance dose
for the main indication based upon an analysis of the medical
literature. DDDs are presented not as a recommended dose
but only as a measurement tool. Drug exposure is generally
expressed as DDDs11.000 populationlday. An estimate for a
given drug would be calculated as follows:
1) Total kilograms of drug available during the year +
DDD for drug = total DDDdyear;
2) Total DDDs/year + 365 = DDDs/day;
3) DDDs/day + population size = DDDs/person/day ;
and
4) DDDs/person/day X 1,000 = DDDs/1,000 populationlday.
DDDs established by European researchers (5) were used
where possible; however, DDDs have not been published for
meclofenamate, piroxicam, and zomepirac, so the official
labeling for these drugs was used.
Figures were also calculated from National Prescription .4udit data on the average prescribed daily doses (PDDs)
in the US as specified by the prescribing physicians. Since
the daily doses actually prescribed for American patients are
higher than the defined daily doses for most NSAIDs,
estimates of PDDs/l ,000 population/day were also calculated. More detailed information on the use and limitations of
pharmaceutical purchase data for assessing population exposure is presented elsewhere (6).
The 2 preceding databases provide information on
the extent of drug utilization, but not on more qualitative
aspects of drug use, such as who is using the drug or what
the drug is being used for. The National Disease and
Therupeutic Index (NDTZ) (3) does give this type of information. The NDTI is based on case history information from
over 2,000 office-based physicians who report on each
private patient seen or contacted in any way. Since between
4-36% of NSAIDs recorded during a physician-patient
cont,act are issued by means other than a formal prescription
(e.g., hospital order, sample), drug reports do not equate to
written prescriptions. In addition, refill prescriptions not
involving a physician-patient contact are not included in
NDlI data. By convention, the NDTI employs the term
“mentions” for such reports; mentions reflect usage, but
687
should not be interpreted as directly equivalent to prescriptions or patients. We used data from the National Disease
and Therapeutic Index to characterize the age and sex
distributions of NSAID users, associated diagnoses (as
coded in the International Classification of Diseases-Seventh Revision [7]),drug therapy for arthritis, and concomitant use of other drugs.
All 3 databases group individual drug products according to the Uniform System of Classification (developed
by IMS America, Ltd. in conjunction with the Pharmaceutical Marketing Research Group, Ambler, PA). Within this
system, the category for systemic antiarthritics includes
some products that are not NSAIDs (i.e., gold therapies). In
addition, some NSAIDs are categorized as synthetic nonnarcotic analgesics rather than systemic antiarthritics (mefenamic acid and zomepirac), while some NSAIDs appear in
both categories. For example, naproxen is categorized and
promoted as an antiarthritic under the trade name Naprosyn
and as an analgesic under the trade name Anaprox. All
estimates presented in this paper are based on analgesic and
antiarthritic data combined, with the exception of those data
for concomitant use of other drugs.
Table 1. Prescriptions for nonsteroidal antiinflammatory drugs in
1983*
Generic and trade
names
Fenoprofen
Nalfon
Nalfon-200
Ibuprofen
Motrin
Rufen
lndomethacin
Indocin
Indocin SR
Meclofenamate
Meclornen
Mefenamic acid
Ponstel
Naproxen
Naprosyn
Anaprox
Oxyphenbutazone
Tandearil
Phen ylbutazone
Azolid
Azolid-A
Butagen
Butazolidin
Butazolidin alka
Piroxicam
Feldene
Sulindac
Clinoril
Tolrnetin
Tolectin
Tolectin DS
Zomepirac
Zomax
Total no.
prescriptions
(in millions)
7% new prescriptions
Mean no.
of tablets in
prescription
3.3
47
56.1
19.8
52
56.8
9. I
50
51.3
1.8
48
58.6
0.7
59
29.5
11.5
51
45.6
0.6
73
35.8
2.6
76
34.0
7.6
41
28.3
5.8
41
53.7
2.4
45
61.1
I .4
67
35.4
* Based on data from reference
no. I
688
BAUM ET AL
Figure 1. Prescriptions for nonsteroidal antiinflammatory drugs (by chemical class) dispensed by retail
pharmacies from 1973-1983.
RESULTS
Table 1 provides a breakdown of total NSAID
prescriptions in 1983 by individual geperic name and
also indicates the percentage of each that were new
prescriptions (rather than refills). The latter data provide an indication of whether a drug is for long-term
use or for acute conditions, but should be used for
comparative purposes (rather than taken as an estimate of the percentage of use that is actually new
therapy) because some portion of new prescriptions
are written for continued therapy. The percentage of
new NSAID prescriptions was around 50%, with 4
exceptions: mefenamic acid, oxyphenbutazone, phenylbutazone, and zomepirac had a higher percentage
of new prescriptions.
Differences in the mean number of tablets or
capsules in a prescription paralleled differences in the
" % new Rxs," with fewer units included in prescriptions for mefenamic acid, oxyphenbutazone, phenylbutazone, and zomepirac. Prescription size was also
relatively low for piroxicam, but was comparable with
the other NSAIDs considering its once-a-day dosage.
Trends in NSAID use. Figure 1 displays data
from the NPA on trends in the total number of
prescriptions. For simplification of graphic display,
data were grouped into 5 chemical classes: pyrazolones, anthranilic acids, indole derivatives, propionic
acid derivatives, and oxicam.
In 1983, there were 12 nonsalicylate NSAIDs
on the market (zomepirac was withdrawn during the
latter part of the year). In 1973, there were only 4. The
bottom bar on the graph represents the 2 pyrazolones:
phenylbutazone (approved by the FDA in 1952) and
oxyphenbutazone (approved in 1960). No new pyrazolones have since been introduced, and there has been a
steady decline in the number of prescriptions for these
drugs over the 11-year period. One anthranilic acid,
mefenamic acid, which was approved in 1965, was
available in 1973. Mefenamic acid is a very small
proportion of the class, and as will be discussed later,
is not used in the same way as the other NSAIDs. In
689
UTI[LIZATION OF NSAIDs
Table 2.
Population exposure to nonsteroidal antiinflammatory drugs
DDD
(mg)t
Drug
kg*
Fenoprofen
Ibuprofen
Indomethacin
Meclofenamate
Mefenamic acid
Naproxen
Oxyphenbutazone
Phenylbutazone
Piroxicam
Sulindac
Tolmetin
Zomepirac
Total
98,600
473,600
15,500
6,800
5,000
149,700
2,100
7,600
3,800
52,400
5 1,800
6,400
DDDs/
1,000 POPUlatiodday
1,200
800
0.97
6.98
1.83
0.40
0.06
3.53
0.08
0.30
2.24
3.09
0.87
0.19
20.54
100
2009
1,000
500
300
300
209
200
700
4009
* Total kilograms of drug purchased by retail pharmacies
t DDD = defined daily dose.
t Based on data from reference no. 1. PDD = prescribed
PDDd
I ,~O~/POPUlation/day
US PDD
(mdS
0.74
3.26
1.72
0.33
0.06
2. I4
0.07
0.24
2.04
1.59
0.52
0. I8
12.89
1,563
1,715
106
245
1,025
825
352
371
22
388
1,165
430
and hospitals during 1983 (2).
daily dose.
8 No published DDD; developed in-house based on official labeling.
mid-1980 the second anthranilic acid, meclofenamate,
was approved.
Indomethacin was the only other NSAID on the
market in 1973. Although there has been a decline in
prescriptions for indomethacin over the past 10 years,
it still ranks third among the 12 NSAIDs. Three
additional indole derivatives have been approved by
the FDA since 1973: tolmetin in March 1976, sulindac
in November 1978, and zomepirac in October 1980.
The first propionic acid derivative, ibuprofen,
was approved in September 1974. Two additional
members of this class, naproxen and fenoprofen, were
intralduced in 1976. In April 1982, piroxicam was
approved and represented a new chemical class. Benoxaprofen, a propionic acid derivative, was also approved in April 1982, but was withdrawn later that
year and, as noted previously, is not included in the
current data.
Table 3. Drugs used concomitantly with antiarthritic nonsteroidal
antiinflammatory drugs (NSAIDs)*
-~
Used alone
Used with other druga
Corticoids
Codeine and combination analgesics (oral)
Muscle relaxants without analgesics
Othier NSAI antiarthritics
Propoxyphenes
Aspirin, APC, etc.
--
' NSAIDs
% of mentions
68
32
6
4
3
3
2
I
categorized in the Uniform System of Classification (7)
as synthetic non-narcotic analgesics rather than systemic antiarthritics are not included. Based on data from reference no. 3. APC =
acetylsalicylic acid, phenacetin, and caffeine.
The number of prescriptions for NSAIDs as a
group increased steadily from 1973 to 1982, but decreased in 1983. This decrease is entirely attributable
to the withdrawal of zomepirac from the market in
1983. If zomepirac use is not considered in the estimates, prescriptions for the remaining NSAIDs increased 2.2% from 1982 to 1983.
As noted previously, the NPA methodology
was revised in 1981, so 1980-1981 changes should be
interpreted with caution; however, the 1981 data
shown in Figure 1 appear to be fairly congruent with
overall trends for NSAID use.
Population exposure. Table 2 presents results of
defined daily dose analyses for NSAIDs, using a US
civilian population estimate of 232,286,000 as of July 1,
Table 4. Age and sex distributions (%) of patients using individual
nonsteroidal antiinflammatory drugs*
Sex
Age
M
F
0-9
10-19
20-39
40-59
60+
35
Fenoprofen
34
Ibuprofen
49
Indomethacin
36
Meclofenamate
3
Mefenamic acid
33
Naproxen
Oxyphenbutazone 50
48
Phenylbutazone
32
Piroxicam
34
Sulindac
37
Tolmetin
41
Zomepirac
65
66
51
64
97
67
50
52
68
66
63
59
-
3
6
2
4
35
5
2
2
1
2
23
28
21
18
53
27
33
28
10
19
20
32
32
27
32
33
7
29
37
34
33
28
38
35
42
39
45
44
4
39
28
36
56
51
38
26
1
-
-
-
* Based on data from reference no. 3.
4
7
BAUM ET AL
1983 (8). The first column gives the total kilograms of
each drug purchased by retail pharmacies and hospitals during 1983, and the second column displays the
defined daily doses established by European researchers or derived from the official labeling. The data on
DDDs/l ,000 populationlday indicated that there was a
total of 20.54 NSAID DDDs/l,OOO population/day in
1983, or enough drug quantity to provide daily treatment for over 2% of the US population.
However, this i s an overestimate of actual
population exposure since there seem to be considerable differences between what is prescribed in the US
and the European DDDs. Prescribed daily doses in the
US for ibuprofen, naproxen, sulindac, and tolmetin
are all at least 50% higher than the established DDDs
(Table 2). Ibuprofen is particularly discrepant, with a
prescribed daily dose more than twice its defined daily
dose. Prescribed daily doses are within the range of
recommended doses given in the official labeling for all
NSAIDs except piroxicam, which has a PDD of 22 mg
and a recommended daily dose of 20 mg. Estimates of
population exposure calculated with prescribed daily
doses rather than defined daily doses indicate a total of
12.89 PDDs/l,OOO population/day. In percentage
terms, enough NSAIDs were purchased by drugstores
and hospitals to treat 1.29% of the entire civilian
population each day in 1983 (or almost 3 million people
daily). Similarly, enough ibuprofen was available on
an average day to treat about 0.3% of the population
(over three-quarters of a million people).
Although the estimates based on prescribed
daily doses are more accurate indicators of overall
NSAID exposure in the US population, it is important
to also describe usage based on defined daily doses.
Since DDDs are standardized technical units of measurement that facilitate comparisons internationally,
as well as on regional or local levels, analyses using
the DDD methodology should always be included.
Depending on the purpose of the research, any suspected discrepancies can then be investigated in more
depth, as was done here using prescribed daily doses.
Concomitant use of other drugs. Table 3 presents data from the National Disease and Therapeutic
Index on the categories of drugs that are most often
used concomitantly with NSAIDs. In contrast with
other data discussed in this review, only those
NSAIDs classified as antiarthritics are included because it was not feasible to combine these data across
categories. Antiarthritic NSAIDs were used alone
about two-thirds of the time and with other drugs
about one-third of the time.
Age and sex distributions. The age and sex
distributions of NSAID users are displayed in Table 4.
Women accounted for 60% of all NDTZ drug mentions
in 1983, and are generally more likely than men to use
NSAIDs as well. Only indomethacin, oxyphenbutazone, and phenylbutazone approached equal use by
men and women. Mefenamic acid was used almost
exclusively by women. NSAIDs were almost never
used by children under 10 years of age, and except for
mefenamic acid, the percentage of NSAIDs used by
children aged 10-19 years was low. Eighty-eight percent of mefenamic acid mentions were for patients
aged 10-39 years. Use of zomepirac and oxyphenbutazone peaked in the 40-59 age group and decreased
among patients 60 years or older, whereas the percent-
Table 5. Diagnoses for diseases of bones and organs of movement (DBOM) associated with
nonsteroidal antiinflammatory drug “mentions”*
% of specific diagnoses
Dm2
Fenoprofen
Ibuprofen
lndomethacin
Meclofenamate
Mefenamic acid
Naproxen
Oxyphenbutazone
Phenylbutazone
Piroxicam
Sulindac
Tolmetin
Zomepirac
Arthritis
NOS
Osteoarthritis
13
I1
13
13
16
14
13
19
Rheumatoid
arthritis
6
3
5
6
-
-
-
11
4
5
23
17
14
17
7
1
-
* Based on data from reference no. 3. NOS
5
4
27
22
20
5
=
10
7
7
I
not otherwise specified.
Bursitis
6
7
11
8
% of
all DBOM
59
49
57
61
-
-
8
23
22
5
56
43
47
78
71
67
17
10
11
4
UTILIZATION OF NSAIDs
69 1
Table 6 . Diagnoses associated with 10% or more of drug “mentions” for any nonsteroidal
antiinflammatory drugs*
% of all associated diagnoses
Drug
Fenoprofen
Ibuprofen
Indomethacin
Meclofenamate
Mefenamic acid
Naproxen
Oxyphenbutazone
Phenylbutazone
Piroxicam
Sulindac
Tolmetin
Zomepirac
DBOM
Sprains/
strains
Surgical
aftercare
12
5
5
4
3
2
4
4
4
3
4
3
19
59
49
57
61
10
6
8
-
1
56
43
47
78
71
67
17
9
8
10
3
7
13
16
* Based on data from reference no. 3. DBOM
=
ages were comparable in these 2 age groups for
to1me:tin and phenylbutazone. The percentage use for
the other NSAIDs increased with age.
Diagnosis profiles. Age and sex distributions
will frequently vary with different uses of a drug, and
Tables 5 and 6 present NDTI data on diagnoses
(categorized in the International Classijication of Disease, or ICD7 [7]) associated with each NSAID. All
Table 7.
--
Drug therapy prescribed for arthritis patients”
Drug category
No drug therapy
Nonsteroidal antiiflammatory drugs
Ibuprofen
Naproxen
Piroxicam
Sulindac
Indomethacin
Fenoprofen
Tolnnetin
Meclofenamate
Zomepirac
Phen ylbutazone
Ox yphenbutazone
Mefenamic acid
Aspirin, APC, etc.
Plain corticoids (oral)
Plain corticoids (injectable)
Codeine and combination analgesics (oral)
Propox yphenes
Other over-the-counter analgesics
Gold therapy
% of all
arthritis
patient visits
15
55
II
11
10
7
7
3
3
3
1
1
I
12
6
5
5
4
3
3
* Includes ICD7 (7) diagnoses of acute pyogenic arthritis, acute
nonpyogenic arthritis, rheumatoid arthritis, spondylitis ankylopoietica, osteoarthritis, spondylitis osteoarthritis, arthritis not otherwise specified, and other specified arthritis. Based on data from
refererice no. 3. APC = acetylsalicylic acid, phenacetin, and caffeine.
Gout
-
1
10
-
I
6
7
1
2
-
Dysmenorrhea
1
6
2
59
7
-
3
diseases of bones and organs of movement.
specific diagnoses that accounted for at least 10% of
the total diagnoses associated with any NSAID are
included in the 2 tables.
As might be expected, NSAIDs are used largely
for the ICD7 class “diseases of bones and organs of
movement.” As indicated in Table 5, arthritis not
otherwise specified (NOS), osteoarthritis, rheumatoid
arthritis, and bursitis were the most frequently mentioned specific diagnoses within the broader diagnosis
class. Oxyphenbutazone and phenylbutazone were
less likely to be used for arthritic conditions and more
likely to be used for bursitis, while most of the other
NSAIDs were more likely to be used for arthritic
conditions. ‘The entire diagnosis class accounted for
practically none of the use of mefenamic acid and for
only 17% of all diagnoses associated with the use of
zomepirac.
Table 6 provides a broader diagnostic profile
and shows the conditions for which mefenamic acid
and zomepirac are most often used. Dysmenorrhea
accounted for 59% of the diagnoses associated with
the use of mefenamic acid, whereas sprains, strains, and
surgical aftercare represented over one-third of diagnoses associated with zomepirac. Diagnoses commonly associated with zomepirac usage that do not appear
in Table 6 were mainly those included in the general
diagnostic classes of “accidents and poisonings” (e.g.,
fractures, contusions, lacerations) and ‘‘symptoms
and senility” (e.g., back pain, headache, chest pain).
Drug treatment for arthritis. The National Disease and Therapeutic Index estimated that there were
29 million visits by patients for the broad diagnosis of
arthritis in 1983. Four specific diagnoses represented
96% of this total: osteoarthritis (40%), arthritis NOS
BAUM ET AL
692
(29%), rheumatoid arthritis (18%), and spondylitis
osteoarthritis (9%). About 55% of the total number of
visits involved prescription NSAID therapy. Only 15%
of the patients were not given some type of drug
therapy. Percentages for individual NSAIDs and other
drug categories are presented in Table 7.
DISCUSSION
Utilization patterns are fairly similar for 8 of the
12 NSAIDs. They are basically used to treat arthritic
conditions in older patients. Mefenamic acid differs
strikingly; almost 60% of its use was for treatment of
dysmenorrhea, and it was virtually never used in the
treatment of arthritis. Women accounted for 97% of
the use of mefenamic acid and 88% of its use was in the
IO-39-year age group.
Zomepirac, phenylbutazone, and oxyphenbutazone also differ from the other NSAIDs and are similar
to one another and to mefenamic acid in several ways.
They were less likely to be used for treatment of
elderly patients and more likely to be used to treat
acute conditions. The proportion of new prescriptions
was higher and the average prescription size was lower
for these drugs compared with other NSAIDs. The
percentage of use for arthritis was relatively low for all
3 drugs. Bursitis was the specific diagnosis most
frequently associated with both phenylbutazone and
oxyphenbutazone, and surgical aftercare was the main
diagnosis for which zomepirac was used. A high
proportion of zomepirac was also used for various pain
symptoms and accidents.
As a class, the NSAIDs are among the most
widely used drugs in current practice. In 1983, enough
NSAIDs were available to treat almost 3 million
people daily. Their use has nearly tripled over the past
10 years and continues to grow. This particular market
appears to be an elastic one: with few exceptions, each
new product introduced expands the market rather
than detracting from the existing products. The
unavailability of zomepirac in the latter part of 1983
was not compensated for by an increase in the use of
other NSAIDs (probably because zomepirac had a
different diagnoduse pattern). Whether the market
will continue to expand with introduction of new
NSAIDs remains to be seen.
REFERENCES
1. National Prescription Audit. Ambler, Pennsylvania, IMS
America, Ltd., 1983
2. The US Pharmaceutical Market-Drugstore and Hospital
Purchases. Ambler, Pennsylvania, IMS America, Ltd.,
1983
3. National Disease and Therapeutic Index. Ambler, Pennsylvania, IMS America, Ltd., 1983
4. Bergman U, Grimsson A, Wahba AHW, Westerholm B,
editors: Studies in Drug Utilization. Copenhagen, World
Health Organization Regional Office for Europe, 1979
5. Nordic Council on Medicines: Nordic Statistics on Medicine. Part 11. Uppsala, Nordic Council on Medicines,
1982
6. Kennedy DL, Forbes MB, Baum C, Jones JK: Antibiotic
use in U.S. hospitals in 1981. Am J Hosp Pharm 40:797801, 1983
7. World Health Organization: Manual of the International
Classification of Disease, Injuries, and Causes of Death.
Geneva, World Health Organization, 1957
8. Estimates of the population of the United States July 1,
1981 to 1983. United States Bureau of the Census.
Advance Report. Population estimates and projections,
Series P-25, No. 944, January 1984
Документ
Категория
Без категории
Просмотров
2
Размер файла
697 Кб
Теги
drug, utilization, nonsteroidal, antiinflammatory
1/--страниц
Пожаловаться на содержимое документа