26

Nonsteroidal Anti-Inflammatory Drug Usage and
Gastrointestinal Outcomes in the Republic of Serbia
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by Michigan University on 10/28/14
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Marina Petric
Ljiljana Tasic
Stevan Sukljevic
ABSTRACT. This study assessed the utilization of prescription and over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) as well as the rate of self-medication with diclofenac,
ibuprofen, and naproxen in the Braneechevo District of the Republic of Serbia. Estimation of
gastrointestinal (GI) disease (morbidity) trends and GI toxicity–associated hospitalization were
studied and direct costs due to NSAID-induced GI toxicity are presented. This descriptive, retrospective study addressed drug use and outcomes between 2004 and 2006 documented in the Health
Insurance Fund database of the Pozarevac Public Pharmacy in the Pozarevac Public Health Centar
of the Braneechevo District, which includes 200,503 inhabitants. Data type/selection were defined
daily doses (DDD) per 1000 inhabitants per day for utilization of drugs, number of patients with
ICD-9 diagnosis codes for GI disorders; GI hospitalization count (average annualy length of stay
[in days] and number of GI hospitalizations); direct cost of hospital care. The OTC diclofenac
use showed an increasing tendency: 6.2279; 6.5983; 8.2911 DDD units, as well as the utilization
of OTC ibuprofen: 2.4389, 2.4899, 2.5776 DDD units, respectively (2004–2006), whereas OTC
naproxen had relatively low utilization . In the same period, GI morbidity decreased: 9636, 7982,
7806, respectively, and the number of GI morbidity-associated hospitalizations increased 10.18%
in 2005 and 15.06%, in versus 2004. The costs of GI morbidity-associated hospitalizations increased: 12.20% (2005) and 94.51% (2006), compared to 2004 costs with a positive correlation
between utility of diclofenac and ibuprofen (self medication) and increased GI hospitalizations in
Braneechevo.
KEYWORDS. Costs, gastrointestinal (GI), nonsteroidal anti-inflammatory drugs (NSAIDs;
diclofenac, ibuprofen, naproxen), over-the-counter (OTC), utlization, Serbia
Marina Petric, BS Pharm, is a pharmaceutical care specialist and research assistant in the Faculty of Pharmacy,
University of Belgrade, Belgrade, Republic of Serbia.
Ljiljana Tasic, MSPharm, PhD, is an Associate Professor of Pharmacy Administration and Practice and Head,
Department of Social Pharmacy and Pharmaceutical Legislation, Faculty of Pharmacy, University of Belgrade,
Belgrade, Republic of Serbia.
Stevan Sukljevic, BS Pharm, is with the Public Pharmacy Pozarevac, Pozarevac (Branicevo region), Republic
of Serbia..
Address correspondence to Ljiljana Tasic, MS Pharm, PhD, Department of Social Pharmacy and Pharmaceutical
Legislation, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Republic of Serbia
(E-mail: [email protected]).
Preliminary data from this study were presented at the International Society for Pharmacoeconomics and
Outcomes Research (ISPOR) 10th Annual European Congress, Dublin, Ireland, October 2007. The authors express
appreciation to Dusica Tasic for assistance with English translation.
40
Journal of Pain & Palliative Care Pharmacotherapy, Vol. 23(1), 2009
Available online at http://informaworld.com/JPPCP
C 2009 by Informa Healthcare USA, Inc. All rights reserved.
doi: 10.1080/15360280902728203
M. Petric et al.
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INTRODUCTION
The International Association for the Study
of Pain has defined pain as “an unpleasant sensory and emotional experience associated with
actual or potential tissue damage, or described in
terms of such damage.”1 Acute pain can be described as a symptom of a disease process and a
biological function that allows patients to avoid
or minimize injury. Chronic pain, on the other
hand, may be considered a disease in its own
right rather than a symptom.
Nonsteroidal
anti-inflammatory
drugs
(NSAIDs), which act through cyclooxygenase
(COX) inhibition, are used widely to relieve
pain with or without inflammation in acute and
chronic musculoskeletal disorders. Single doses
of NSAIDs produce analgesia comparable
to acetaminophen (paracetamol), whereas in
higher doses they have both sustained analgesic
and anti-inflammatory effects. This makes them
particularly useful for the treatment of pain
associated with inflammation. NSAIDs are indicated for the relief of dysmenorrhea, toothache,
some types of headaches, and pain caused by
secondary bone tumors, many of which produce
boney lysis and prostaglandin release.1
This wide range of indications makes
NSAIDs very frequently used drugs; they are
among the most widely used drugs in the world.
More than 30 million people worldwide consume prescription NSAIDs daily.2 A telephone
survey conducted by the National Consumers
League estimated that almost 60 million adults
in the United States take over-the-counter (OTC)
pain relievers every day.3
Among the most frequent NSAID-associated
side effects are gastrointestinal (GI) tract bleeding, ulcers, perforations, and nephrotoxicity,
with increased risk of GI adverse effects in
elderly patients who take the drugs regularly.
Due to pain, patients often experienced difficulties discontinuing NSAIDs treatment even
in the presence of adverse GI side effects.
Thomsen et al. estimated that among 7232
patients hospitalized for bleeding peptic ulcers,
28% were current NSAID users.4 Insúa et al.
established that NSAID exposure was associated with an increased risk of hospitalization
for peptic ulcer disease (PUD) (odds ratio [OR],
5.20; 95% confidence interval [CI], 3.31–8.15);
the risk increased for both severe PUD and
moderate PUD.5
41
Smalley et al. investigated the hospitalization
rates for ulcers among nonusers of NSAIDs and
current users of NSAIDs in the elderly population. The rates of hospitalization were 4.2 and
16.7 per 1000 person-years, respectively, indicating an increased rate among NSAID users
of 12.5 per 1000 person-years (95% CI, 11.4–
13.6).6 Among new users, the ulcer hospitalization rates were 26.3 per 1000 person-years
during the first 30 days of use and 20.9 per
1000 person-years. Over the next 31 to 180
days, NSAID use was associated with excess
ulcer hospitalization rates of 22.1 (95% CI,
18.6–25.6) and 16.7 (95% CI, 13.1–20.1) per
1000 person-years, respectively. For long-term
users (180 days of continuous NSAID use or
more), the ulcer-induced hospitalization rate remained elevated at 15.3, an excess of 12.0
(95% CI, 10.3–13.6) hospitalizations per 1000
person-years.6
OBJECTIVES
This study was conducted to assess the utilization of both OTC and prescription NSAIDs, to
determine the rate of NSAIDs self medication,
to estimate trends in GI morbidity and resultant hospitalization, and to determine the direct
costs of hospital care due to that morbidity in the
Braneechevo District of the Republic of Serbia
between 2004 and 2006.
METHODS
This was a retrospective study of drug use and
outcomes between 2004 and 2006 conducted in
the Braneechevo District, Republic of Serbia,
which has a population of 200,503.7 The claims
database of the Pozarevac Public Pharmacy was
used to determine the utilization rates for prescription and OTC NSAIDs. Prescription drugs
on the reimbursment list can be dispensed only
at the Public Pharmacy according to the Government regulation in Serbia. The Pozarevac Public
Pharmacy is part of a managed care organization (MCO) with network of 25 pharmacies in
the Braneechevo District.
The utilization rates are expressed as defined daily doses (DDD) per 1000 inhabitants
per day. Three NSAIDs: diclofenac, ibuprofen,
and naproxen were evaluated. The utilization ration (UR) (ratio of prescription NSAIDs to OTC
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JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY
NSAIDs) was the parameter used to analyze the
data.
The most common NSAID side effects were
related to the GI tract. Diagnoses monitored were
gastric ulcer, duodenal ulcer, gastritis, and duodenitis (International Classification of Disease 9
[ICD9]); data were obtained from the Pozarevac
Public Health Center of the Braneechevo District. Data on the number of patients with GI
diseases were obtained from the Public Health
Center primary health care facility and for hospitalized patients for the same GI events treated in
Pozarevac General Hospital, a secondary health
care facility. In addition to epidemiological data
on the GI morbidity, direct costs of GI morbidityassocaited hospital care were analyzed. The latter data came from the Republic Health Insurance Fund office for the Braneechevo District
and the Institute for Public Health office for
the Braneechevo District Financial Department
records.
The Student t test was used for the statistical
analysis of the observational data.
RESULTS
From the Public Pharmacy database we
calculated the DDD units for the individual
NSAIDs, as shown in Table 1. Inhabitants of
the Braneechevo District received their prescription NSAIDs from only the Pozarevac Public Pharmacy, whereas they could purchase
OTC NSAIDs from Pozarevac Public Pharmacy
and several private pharmacies. Because OTC
NSAID utilization data from private pharmacies
were not available, we were only able to analyze
the Public Pharmacy data.
The utilization of diclofenac, naproxen,
piroxicam, ibuprofen, ketorolac, meloxicam,
flurbiprofen, tiaprofenic acid, and acetyl salicylic acid was analyzed. The most frequently
used prescription NSAIDs were diclofenac,
ibuprofen, and naproxen. The most frequently
used OTC NSAIDs were diclofenac and ibuprofen; OTC naproxen had relatively low utilization. The utilization of the other NSAIDs was
remarkably less. Therefore, we evaluted only diclofenac, ibuprofen, and naproxen in the next
phase of the investigation.
For prescription diclofenac, the data indicated 30.04 DDD/1000 inhabitants per day,
23.29 DDD/1000 inhabitant per day; and 25.80
DDD/1000 inhabitant per day for 2004, 2005,
and 2006, respectively. The utilization of prescription diclofenac decreased by 22.47% in
2005 and 14.1% in 2006, compared to 2004. The
utilization of prescription ibuprofen was 4.59
DDD/1000 inhabitants per day, 4.51 DDD/1000
inhabitants per day, and 3.16 DDD/1000 inhabitants per day for the 3 consecutive study years
with a decrease of 1.74% in 2005 and 31.15%
in 2006 versus 2004. The utilization of prescription naproxen increased significantly; it was 3.84
DDD/1000 inhabitants per day, 5.26 DDD/1000
inhabitants per day, and 4.77 DDD/1000 inhabitants per day, respectively, during the 3-year
study period, with an increase of 36.78% and
24.03%, respectively, from 2004. To summarize, the prescription utilization for diclofenac
and ibuprofen decreased from 2006 to 2004,
but naproxen use increased in the same period.
Potential explanations for this are the changes
TABLE 1. Utilization of NSAIDs and OTC NSAIDs in the Population of Braneechevo, 2004–2006
2004
2005
2006
Rx (DDD/1000/ OTC (DDD/1000/ Rx (DDD/ OTC (DDD/1000/ Rx (DDD/1000/ OTC (DDD/1000/
day)
day)
1000/day)
day)
day)
day)
Diclofenac
Naproxen
Piroxicam
Ibuprofen
Ketorolac
Meloxicam
Flurbiprofen
Tiaprofenic acid
Acetyl salicyl acid
30.0378
3.8427
0.1983
4.5906
—
6.2279
1.0611
0.2951
2.4389
0.0173
0.0651
0.2863
0.0882
3.6901
23.2883
5.2562
0.4848
4.5085
0.0171
0.0771
0.3511
0.0809
0
6.5983
0.9013
0.3785
2.4899
0.0152
0.0659
0.3298
0.0701
3.5945
25.8018
4.7661
0.5335
3.1596
0.0408
0.1803
0.3833
0.1399
0
8.2911
0.4688
0.2368
2.5776
0.0179
0.0676
0.2267
0.0716
3.1567
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M. Petric et al.
in drug reimburstment eligibility that occured
during the study period and fact that naproxen
was added to the reimburstment list in the
Janury 2005.8 Diclofenac and ibuprofen were
on the reimburstment list throughout the study
period.
OTC NSAIDs are widely used for self
medication. The utilization of OTC diclofenac
was 6.23 DDD/1000 inhabitants per day,
6.60 DDD/1000 inhabitants per day, and 8.29
DDD/1000 inhabitants per day, respectively, in
the 3 years 2004, 2005, and 2006 (Table 1).
The increase in the study period was 5.95%
in 2005 and 33.1% in 2006. The utilization
of OTC ibuprofen was 2.44 DDD/1000 inhabitants per day, 2.49 DDD/1000 inhabitants per
day, and 2.58 DDD/1000 inhabitants per day,
respectively. The increase in the second and
third study period years was 2.09% and 5.9%,
respectively (Table 1). The utilization of OTC
naproxen was 1.06 DDD/1000 inhabitants per
day, 0.9 DDD/1000 inhabitants per day, and 0.47
DDD/1000 inhabitants per day, respectively. The
decrease was 15% and 55.82% in 2005 and 2006,
respectively (Table 1). The utilization of OTC
diclofenac and ibuprofen increased and the utilization of OTC naproxen decreased during the
study period. The utilization of OTC naproxen
was notably less than that of OTC diclofenac
and ibuprofen. Again, this was at least partly
43
attributable to naproxen being added to the reimburstment list in 2005.
The total utilization of diclofenac was
36.04 DDD/1000 inhabitants per day, 29.89
DDD/1000 inhabitant per day, and 34.09
DDD/1000 inhabitant per day, respectively, for
2004, 2005, and 2006 (Table 2). The decrease
in total diclofenac use was 17.6% in 2005
and 5.99% in 2006. The total utilization of
ibuprofen was 7.03 DDD/1000 inhabitants per
day, 6.99 DDD/1000 inhabitants per day and
5.74 DDD/1000 inhabitants per day respectively for the 3 years 2004 to 2006 (Table 2).
The decreased use of ibuprofen was 0.44% and
8.38% in 2005 and 2006, respectively. Total
naproxen use was 4.90 DDD/1000 inhabitants
per day, 6.16 DDD/1000 inhabitants per day, and
5.23 DDD/1000 inhabitants per day respectively
2004, 2005, and 2006 (Table 2). There was an increasing trend in the total utilization of naproxen
with increases of 25.56% in 2005 and 6.75% in
2006.
The share of OTC forms in total diclofenac
use was 17.17%, 22.08%, and 24.31%, respectively, in 2004, 2005, and 2006 (Table 2). That increase is statistically significant (P < .05). The
share of OTC ibuprofen in the total ibuprofen utilization overall was 34.70%, 35.58%,
and 44.92%, respectively, for 2004, 2005, and
2006 (Table 2); the increase is not statisticaly
TABLE 2. Total, Prescription, and OTC Use (DDD/1000/day (%)) for Diclofenac, Ibuprofen, and
Naproxen, 2004–2006
NSAID
Diclofenac
Total
Prescription
OTC
Ibuprofen
Total
Prescription
OTC
Naproxen
Total
Prescription
OTC
Diclofenac + Ibuprofen + Naproxen
Total
Prescription
OTC
2004
2005
2006
Probability∗ (P)
36.0378 (100%)
30,0378 (82,83%)
6,2279 (17,17%)
29.8866 (100%)
23,2883 (77,92%)
6,5983 (22,08%)
34.0929 (100%)
25,8018 (75,69%)
8,2911 (24,31%)
<.05
<.05
7,0295 (100%)
4,5906 (65,30%)
2,4389 (34,70%)
6,9984 (100%)
4,5085 (64,42%)
2,4899 (35,58%)
5,7372 (100%)
3,1596 (55,08%)
2,5776 (44,92%)
>.05
>.05
4.9038 (100%)
3.8427 (78.36%)
1.0611 (21.64%)
6.1575 (100%)
5.2562 (85.36%)
0.9013 (14.64%)
5.2349 (100%)
4.7661 (91.04%)
0,4688 (8.96%)
<.05
>.05
47.9711 (100%)
38.4711 (80.20%)
9.7279 (19.80%)
43.0425 (100%)
33.053 (76.79%)
9.9895 (23.21%)
45.065 (100%)
33.7275 (74.84%)
11.3375 (25.16%)
<.05
<.05
∗
Statistically significant for the utilization of drugs (diclofenac, ibuprofen, naproxen) prescription utilization or OTC utilization versus total
utilization, CI 95%.
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JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY
significantnt (P > .05). The share of OTC
naproxen in the total naproxen utilization was
21.64%, 14.64%, and 8.96%, respectively, for
the 3 years (Table 2); the decrease is not statisticaly significant (P > .05). There was a continual
increase in OTC use for self-medication in the
Braneechevo population with both diclofenac
and ibuprofen from 2004 to 2006.
Diclofenac was the most commonly used
NSAID in the Branicheevo District during the
study period. The share of total utilization of
diclofenac among total NSAID utilization was
68.63% in 2004, 61.61% in 2005, and 68.02%
in 2006. Vlahovic-Palcevski et al. investigated
the utilization of NSAIDs in Croatia (Rijeka)
and Sweden (Stockholm) in 2002. They reported
that diclofenac was the most commonly prescribed drug in these two cities (55% in Rijeka and 25% in Stockholm).9 Diclofenac was
the most commonly used NSAID in all mentioned districts, but the utilization of diclofenac
in the Branicheevo district was greatest, almost
threefold more than in Stockholm. Diclofenac
is a nonselective NSAID associated with numeorus GI and other adverse effects. Health problems and more use of other resources (people,
time, money) can be related to adverse efects
of diclofenac in a population which uses it to a
great degree.
The use of prescription diclofenac was
82.83%, 77.92%, and 75.69%, respectively, in
2004, 2005, and 2006. This the decrease is statisticaly significantnt of (P < .05). The share
of prescription ibuprofen was 65.30%, 64.42%,
and 55.08%, respectively, over the 3 years. That
decrease is not statisticaly significant (P > .05).
The share of prescription naproxen was 78.36%,
85.36%, and 91.04%, respectively, and that increase is statistically significant (P < .05).
We determined the utilization ratio (UR)
of prescription diclofenac to OTC diclofenac;
the UR was 4.8, 3.5, and 3.11, respectively,
for the 3 study years (Table 3). For prescription ibuprofen versus OTC ibuprofen, the
UR was 1.88, 1.81, and 1.22, respectively,
for 2004, 2005, and 2006 (Table 3). For prescription naproxen versus OTC naproxen, the
UR was 3.62, 5.83, and 10.16, respectively,
for the 3-year study period (Table 3). These
results show that use of prescription diclofenac and ibuprofen decreased, prescription
naproxen increased, and OTC naproxen had
low utilization. The OTC diclofenac and OTC
TABLE 3. Utilization ratio (UR) of Diclofenac,
Ibuprofen, and Naproxen Prescription/OTC,
2004–2006
Diclofenac
Ibuprofen
Naproxen
2004
2005
4.8
1.88
3.62
3.5
1.81
5.83
2006
3.11
1.22
10.16
ibuprofen share continually increased. We assumed this was due to physician and patient
prescibing habit and preference, and aggressive
marketing of those drugs by pharmaceutical
industry.
Overall, diclofenac, ibuprofen, and naproxen
use declined throughout the study period. It
was 47.97 DDD/1000 inhabitants per day in
2004, 43.04 DDD/1000 inhabitants per day in
2005, and 45.07 DDD/1000 inhabitants per day
in 2006 (Table 2). The decrease was 10.27%
and 6.06% each year, respectively, compared
to 2004. Total prescription utilization for those
drugs was 38.47 DDD/1000 inhabitant per day
in 2004, 33.05 DDD/1000 inhabitants per a day
in 2005, and 33.73 DDD/1000 inhabitants per
day in 2006, a statistaically significant change.
(P < .05) (Table 2). The decrease was 4.11%
and 2.15 % for 2005 and 2006, respectivly, compared to 2004. Contrary, total OTC utilization
increased from 9.73 DDD/1000 inhabitants per
day in 2004, to 9.99 DDD/1000 inhabitants per
day in 2005, and to 11.34 DDD/1000 inhabitants per day in 2006 (P < .05) (Table 2). The
increase was 2.69% in 2005 and 16.55% in 2006.
The increase in OTC NSAID utilization in 2006
exceeded the decrease in prescription NSAID
use (2.15% versus 16.55%).
A burden of disease analysis was conducted
for Serbia in the period 2003 to 2006.10,11 During that time, improvements occurred in medical care and the health system in general.
The Ministry of Health formed several Expert
Committees to prepare guidelines for treatment
of the most frequent diseases. A 2000 to 2005
initiative aimed to decrease prevalence of GI
tract bleeding and culminated in the publication
of a National Guideline for GI tract bleeding
in 2005.12 This guideline was intended mainly
for primary care physicians, but it contains
recommendations relevant to hospital care as
well. GI tract bleeding mortality has been reportred as 7% to 10% worldwide even with
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M. Petric et al.
the best treatment.12 Some of recommendations
note that the most at-risk patients are those
who intermittently use NSAIDs and anticoagulant users.12 Peptic ulcers account for 30% to
50% of GI tract bleeds.12 The Serbian National
Guideline for GI tract bleeds suggests stopping
all drugs that may generate bleedings (NSAID,
asprin, anticoagulants) when patients experience
severe, moderate, or mild bleeding. The Guideline suggests that patients who have bleeding
ulcers associated with NSAID use must stop using these drugs. The Guideline suggests that patients who require NSAIDs as first-line therapy
for their primary disease should receive ibuprofen with a proton pump inhibitor or a COX2–selective NSAID.12 Physicians complied
with the Guideline, resulting in decreased prescription but OTC NSAID utilization increased
in the same time period. These data indicate
that the patients did not change their habits, and
the overall drug use was not consistent with the
Guideline or optimal therapy. Patients were not
well informed on safety profile of NSAIDs for
self-medication.
GI Morbidity and Hospitalization Direct Care
Hospital Costs
We investigated the GI disease trends: gastric
ulcers, duodenal ulcers, gastritis, and duodenitis
in the Braneechevo District from 2004 to2006.
The numbers of patients with these dosorders
were 9636, 7982, and 7806, respectively. GI
disease morbidity decreased 17.16% and for
18.99%, respectively, from 2004. We investigated the number of GI hospitalizations for the
same indications in Pozarevac General Hospital of the Braneechevo District. The number of
GI hospitalizations were 285, 314, and 328, respectively, for 2004, 2005, and 2006. Contrary
to the decreased GI morbidity, the number of GI
hospitalization increased 10.18% and 15.09%,
respectively, in 2005 and 2006 compared to
2004.
The decrease in GI morbidity and mortality
from of GI disorders was consistent with National Guideline for GI tract bleeds. The increase
in GI hospitalizations indicates problems and exposure to risk factors that should be further investigated. We have speculated that the increase
in self-medication with NSAIDs, particulary diclofenac and ibuprofen, may be the reason for
ireased GI disease-associated hospitalizations.
45
From the hospital records, we collected data
on patients who were hospitalized because of
GI events associated with NSAIDs use. We examined 456 records that indicated GI disease
associated hospitalizations, and found only 40
users of NSAIDs among them (Table 4). Unfortunately, the records do not state whether the patients used prescription or OTC NSAIDs. Only
one record had a statement the patient hadn’t
been a NSAIDs user. All other de-identified
patient records (415) lacked documentation on
whether or not the patients had used NSAIDs.
This lack of documentation is an important limitation that prevents us from concluding that
the increase in OTC NSAID utilization was the
reason for the increase in GI hospitalizations.
The hospital patient records in Serbia are not
standardized, and do not routinely include drug
use on hospital admission, during hospitalization, and at discharge.
Neither physicians nor pharmacists fully
control NSAID use in Serbia. Aspirin and
other NSAID use can be the reason for GI
bleeding.13–15 The available data do suggest
an association between the increased use of
OTC NSAIDs in the Braneechevo and increased
GI toxicity–associated hospitalizations. Unfortunately, the lack of linked patients’ medical
records at the primary and secondary levels of
TABLE 4. GI Hospitalization of Patients Users
of NSAIDs
NSAID
Diclofenac
Ibuprofen
Naproxen
Acetyl salicylic acid
Piroxicam
Meloxicam
Diclofenac + ibuprofen
Diclofenac + acetylsalicylic
acid
Ibuprofen + acetylsalicylic
acid
Diclofenac + ibuprofen +
acetylsalicylic acid
Antirheumatic drug (drug
name not specified)
Number of patients
hospitalized for
gastrointestinal
NSAID-associated
disorders
10
3
3
9
2
1
2
1
2
1
6
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JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY
health system limits our ability to make final conclusions. Future implentation of electronic medical records will allow database development to
integrate patient medical records at the primary
and secondary care levels, enabling these types
of investigations in more detail. We did document a large increase in the number of GI hospitalisation as well as higher expenseses for hospital care. The average cost per patient per day for
GI hospitalization was US $73.39, $75.35, and
$123.98, respectively, for 2004, 2005, and 2006,
representing an increase of 2.67% in 2005 and
68.93% in 2006 compared to 2004. The costs of
hospital care per day were US $8.15, $8.30, and
$17.71, respectively, for 2005 and 2006. The average hospital length of stay was 9 days in 2004
and 2005, and 7 days in 2006.
Additionally, we calculated the total annualy costs for the GI hospitalizations for each
year. The annualy costs were US $20,904.75,
$23,455.80, and $40,662.16, respectively, for 3
years observed. The costs of GI hospitalization
increased in the study period by 12.20% in 2005
and 94.51% in 2006 compared to 2004. This
was a surprisingly large increase, especially in
light of the average length of stay decreasing by
2 days in 2006. Hospitalization incidence and
costs increases place a strain on the resources of
the Serbian Health Insurance Fund.
There are two current studies on the burden of illness in Serbia conducted with limited
health economic data.10,11 Additional investigations of GI tract toxicities and treatment patterns
are needed, especially pharmacoeconomic costeffectiveness analyses, focusing on NSAIDs.
The self-medication trends with OTC NSAIDs
and the rationality of their use must be investigated to benefit both individual patients and
society.
Other studies have shown a direct correlation between the GI hospitalization and NSAID
use. Sorensen et al. estimated that the risk of GI
hospitalization in the Danish population using
low-dose aspirin (100 to 150 mg daily) was 2.3
times greater that the incidence in the general
population.16 Low-dose aspirin in the presence
of other NSAIDs resulted in 5.6 times greater
incidence of GI hospitalization.16 Insúa et al.
examined the association between an exposure
to nonselective NSAIDs and hospitalization for
peptic ulcer disease (PUD) among older adults in
Argentina.5 Those studies showed that NSAID
exposure was associated with increased risk of
hospitalization for PUD (OR, 5.20; 95% CI,
3.31–8.15). The risk increased for both severe
PUD (OR, 4.24; 95% CI, 2.29–7.87) and moderate PUD (OR, 6.08; 95% CI, 3.09–11.96).5 Evidences supports an association between NSAID
use and GI mortality, and increasing widespread
OTC NSAID use without awareness among consumers taking the drugs of the risk of GI complications. These factors support the need for
monitoring and counseling on NSAID use in
Serbia.
CONCLUSION
Available data indicate a decreased trend toward use of diclofenac, ibuprofen, and naproxen
in the study period of 2004 to 2006. In the
same period, there was a decrease of GI morbidity in the population of Braneechevo District.
It was consistent with the National Guideline
for GI bleeding, which was designed to improve
the utilization of these drugs. Concurrently,
the utilization of OTC diclofenac and ibuprofen increased. Self-medication with those two
drugs was documented by an increased UR.
The number of GI hospitalizations also increased and there appears to be both increased
hospitalization incidence and increased burden
on the Health Insurance Fund of Republic of
Serbia. Whether increased self-medication with
NSAIDs was the cause of the increase in the
number of GI hospitalizations in the population of the Braneechevo District deserves further
investigation.
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RECEIVED: 4 February 2008
REVISED: 8 October 2008
ACCEPTED: 5 November 2008