The Burden of Gastrointestinal and Liver Diseases, 2006

Article (PDF Available)inThe American Journal of Gastroenterology 101(9):2128-38 · October 2006with103 Reads
DOI: 10.1111/j.1572-0241.2006.00723.x · Source: PubMed
Abstract
Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians, policymakers, and researchers. To describe the epidemiology of gastrointestinal and liver diseases in the United States using data from privately and publicly held databases. We collected data from the National Center for Health Statistics, the National Ambulatory Medical Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease incidence from these databases, and extracted data specific to gastrointestinal diseases. Because of the high costs associated with medications used to treat gastrointestinal diseases, we also include in this year's report a special section on pharmacoepidemiology and pharmacoeconomics. Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis following. Americans spend in excess of US dollars 10 billion/yr on proton pump inhibitors (PPIs), and two of the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent changes, likely reflecting both new drug entries into the field, as well as drug marketing. The number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs used for gastrointestinal diseases are among the top 200 generic drugs used in the United States. Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and health-care expenditures of the U.S. population.

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American Journal of Gastroenterology ISSN 0002-9270
C
2006 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2006.00723.x
Published by Blackwell Publishing
CLINICAL REVIEWS
The Burden of Gastrointestinal and Liver Diseases, 2006
Nicholas J. Shaheen, M.D., M.P.H.,
1,3
Richard A. Hansen, Ph.D.,
2
Douglas R. Morgan, M.D., M.P.H.,
1
Lisa M.
Gangarosa, M.D.,
1
Yehuda Ringel, M.D.,
1
Michelle T. Thiny, M.D., M.P.H.,
1
Mark W. Russo, M.D., M.P.H.,
1
and Robert S. Sandler, M.D., M.P.H.
1,3
1
Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine,
2
The School of
Pharmacy, and
3
The School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North
Carolina
BACKGROUND: Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs
for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians,
policymakers, and researchers.
AIM: To describe the epidemiology of gastrointestinal and liver diseases in the United States using data
from privately and publicly held databases.
METHODS: We collected data from the National Center for Health Statistics, the National Ambulatory Medical
Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the
National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on
the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on
causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease
incidence from these databases, and extracted data specific to gastrointestinal diseases. Because
of the high costs associated with medications used to treat gastrointestinal diseases, we also
include in this year’s report a special section on pharmacoepidemiology and pharmacoeconomics.
RESULTS: Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate
a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common
GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related
diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common
cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis
following. Americans spend in excess of $10 billion/yr on proton pump inhibitors (PPIs), and two of
the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent
changes, likely reflecting both new drug entries into the field, as well as drug marketing. The
number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs
used for gastrointestinal diseases are among the top 200 generic drugs used in the United States.
CONCLUSIONS: Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and
health-care expenditures of the U.S. population.
(Am J Gastroenterol 2006;101:2128–2138)
INTRODUCTION
Digestive and liver diseases impose a substantial burden on
Americans. Over two million individuals were hospitalized
with gastrointestinal and liver diseases in 2002. Gastroin-
testinal malignancies are among the most common cancers
suffered by Americans, and colorectal cancer is the number
three cancer killer of both men and women in the United
States (1). In excess of 40 billion dollars of health-care ex-
penditures are used for gastrointestinal diseases annually (2).
Grant Support: This work was supported by NIH K23DK59311-01 (Shaheen) and
P30 DK34987 (Sandler).
Given the impact of these diseases on our society, an up-
dated comprehensive report of gastrointestinal and liver dis-
ease statistics could be useful for clinicians, epidemiologists,
authors, grant applicants, and policymakers. As previously
(3), we have compiled statistics on the morbidity, mortality,
and costs associated with gastrointestinal and liver disease
from various government agencies, as well as proprietary
firms, to create a report of the morbidity, mortality, and costs
of these diseases on the U.S. population.
This report contains a special section focusing on the phar-
macoeconomics andpharmacoepidemiology of gastrointesti-
nal medications. Because medications for gastrointestinal
ailments are among those most commonly used by Amer-
icans, and because the total dollar value of these medications
2128
GI Statistics, 2006 2129
exceeds $10 billion/yr, they are a major contributor to health-
care expenditures in the United States. Readers may also find
the information useful regarding trends in the usage of these
medications.
MATERIALS AND METHODS
We compiled information on causes of death, hospitalization,
clinic visits, cancer incidence, and infectious disease inci-
dence from a variety of publicly and privately held databases.
From these databases, we extracted data regarding gastroin-
testinal diseases and malignancies. In cases where a diagnosis
may or may not indicate gastrointestinal disease, the disease
diagnosis was included in our tabulations. For instance, non-
cardiac chest pain, the number one GI-related cause of dis-
charge after inpatient admission, likely includes subjects with
pain of esophageal origin, as well as costochondritis, pleuritic
inflammation, and a variety of other conditions.
Each database used to compile this report provides data
in a somewhat different format. For each source, the meth-
ods used to compile the data from the source database are
outlined below. For instances where the data were further ag-
gregated after being retrieved from the source database, any
further calculations are also described. When data were ex-
tracted from a publicly available database, the Web site and/or
publication citation of the source are given.
Gastrointestinal Causes of Death
Gastrointestinal causes of death were compiled from the Di-
vision of Vital Statistics, National Center for Health Statistics
(http://www.cdc.gov/nchs/data/statab/mortfinal2001˙workI.
pdf). Causes of death were reported using the International
Classification of Diseases, 10th revision (ICD-10). The
causes of death are determined from death certificates,
which are entered into local and state databases. Data are
transferred to the U.S. Division of Vital Statistics after entry
into a standardized form.
In order to collate the data into clinically applicable diag-
noses, multiple ICD-10 codes were grouped by anatomic site
to create a single disease entity. For instance, colorectal/anal
cancer includes subjects with a cause of death coded as ap-
pendiceal cancer (C18.1), ascending colon cancer (C18.2),
hepatic flexure cancer (C18.3), etc. Cancer diagnoses in the
National Center for Health Statistics database are not further
subdivided by histologic type.
Gastrointestinal Symptoms and Diagnoses
We tabulated the leading gastrointestinal symptoms prompt-
ing an outpatient clinic visit in the United States. Data on
outpatient visits for 2002, the most recently available year,
were collected as part of the National Ambulatory Medi-
cal Care Survey (NAMCS), a yearly national survey spon-
sored by the U.S. Centers for Disease Control and Prevention
(CDC) to provide information about the use of ambula-
tory services in the United States. These data are available
at www.cdc.gov/nchs/about/major/ahcd/ahcd1.htm. We used
the NAMCS to determine the leading symptoms prompt-
ing an outpatient visit, and leading physician diagnoses. Ex-
cluded in NAMCS are federally funded providers, hospital-
based clinics, and emergency department visits.
The survey sampling unit for NAMCS is the provider–
patient encounter in office-based practices. The 2002
NAMCS used a multistage probability design using patient
visits within physician practices sampled from 1,900 geo-
graphically defined primary sampling units. Each provider
was randomly assigned 1 wk from the reporting year. The
study design incorporated a patient visit weight (inflation
factor) to derive national estimates from the survey.
Nearly two-thirds of physicians participating in NAMCS
are primary care providers (Family Practice, Internal
Medicine, Gynecology, Pediatrics). One quarter are from
the following specialties: Surgery, Orthopedics, CV disease,
Dermatology, Urology, Neurology, Ophthomology, Otolary-
gology, and Psychiatry. The remaining specialties, includ-
ing Gastroenterology, are grouped under “Other Specialties.”
Less than 1% of the surveyed practices are Gastroenterology
specialty practices.
Data were collected using specially designed data sheets,
not office billing codes. Symptoms prompting an outpatient
clinic visit were initially expressed in the patient’s own words,
and subsequently coded by office staff using the Reason for
Visit Classification for Ambulatory Care (RVC) (4). The prin-
cipal, or first listed, reason for appointment was used in the
analysis. An additional two reasons could be listed, but were
excluded from the current analysis. Physician diagnoses were
also initially entered as free text, then coded by central coders.
“Upper abdominal pain” was used to estimate dyspepsia.
“Heartburn and indigestion” was used to estimate reflux dis-
ease, but may have included patients with isolated dyspepsia.
Symptoms of abdominal swelling, changes in girth, mass,
and fullness were combined under “abdominal distension.”
Anorectal symptoms were also grouped, with the exceptionof
rectal bleeding. Gastroenteritis included both infectious and
noninfectious forms. Dyspepsia and gastritis were grouped
together. Diverticular disease included both diverticulosis
and diverticulitis. Physician diagnoses were obtained from
the patient encounter forms according to the International
Classification of Diseases, 9th Revision (ICD-9).
Hospitalization for Gastrointestinal Disorders
The most common inpatient gastroenterology and hepa-
tology discharge diagnoses were compiled from the Na-
tionwide Inpatient Sample (NIS), one of the databases
in the Healthcare Cost and Utilization Project (HCUP)
(http://hcup.ahrq.gov/HCUPnet.asp). The National Inpatient
Sample is available for purchase from HCUP, and contains
data from 1988–2002. The most recent version, NIS 2002,
contains all discharge data from 995 hospitals located in 35
states, approximating a 20% stratified sample of U.S. com-
munity hospitals. The sampling frame for the NIS 2002 is
a sample of hospitals that represents approximately 90% of
2130 Shaheen et al.
Table 1. Leading 20 Gastrointestinal Causes of Death in the United States, 2001
Rank Cause of Death Number of Deaths
ICD-10 Codes
1 Colorectal/anal cancer 56,887 C18.0-C18.9, C19, C20, C21.0-C21.2, C21.8
2 Pancreatic cancer 29,803 C25.0-C25.4, C25.7, C25.9
3 Fibrosis/cirrhosis of liver and hepatic failure NOS 18,283 K72.0-K72.1, K72.9, K74.0-K74.1, K74.3-K74.6
4 Malignant neoplasms of the liver and intrahepatic ducts 13,351 C22.0-C22.4, C22.7, C22.9
5 Esophageal cancer 12,530 C15.0-C15.9
6 Stomach cancer 12,319 C16.0-C16.9
7 Alcoholic liver disease 12,207 K70.0-K70.4, K70.9
8 Vascular disorders of the intestine 9,109 K55.0-K55.2, K55.8-K55.9
9 GI hemorrhage, unspecified 7,804 K92.2
10 Paralytic ileus and intestinal obstruction 5,248 K56.0-K56.7
11 Ulcers (gastric/duodenal/peptic) 4,491 K25.0-K25.7, K25.9, K26.0-K26.7, K26.9, K27.0
K27.3-K27.7, K27.9, K28.4-K28.6, K28.9
12 Acute hepatitis C 4,104 B17.1
13 Diverticular disease 3,438 K57.0-K57.3, K57.8-K57.9
14 Acute pancreatitis 3,075 K85
15 Malignant neoplasms of the gall bladder 1,971 C23
16 Biliary tract cancer 1,630 C24.0-C24.1, C24.8-C24.9
17 Perforation of intestine (nontraumatic) 1,600 K63.1
18 Peritonitis 1,562 K65.0, K65.8-K65.9
19 Cholecystitis 1,475 K81.0-K81.1, K81.8-K81.9
20 Clostridia difficile enterocolitis 1,332 A04.7
Source: National Center for Health Statistics Web site – Mortality Tables
http://www.cdc.gov/nchs/data/statab/mortfinal2001˙workI.pdf.
Of a total of 2,416,425 deaths in 2001.
all hospital discharges in the United States. NIS is the only
national hospital database with charge information on all
patients, regardless of payer, including persons covered by
Medicare, Medicaid, private insurance, and the uninsured.
We queried the database using the following criteria: rank
order of the disease, specific diagnosis by ICD-9-CM, Prin-
cipal Diagnosis, presence in the top 100, number of patient
discharges, for all patients in all hospitals. From this top 100
list, 14 gastroenterology and hepatology diagnoses were iden-
tified. Two similar diagnoses were combined into one table
entry: ICD-9 codes 574.10 (cholelithiasis with cholecystitis
Nec) and 574.00 (cholelithiasis with acute cholecystitis).
Table 2. Leading Gastrointestinal Symptoms Prompting an Outpa-
tient Clinic Visit, 2002
Rank Symptom Estimated Visits
1 Abdominal pain 11,876,657
2 Diarrhea 3,766,261
3 Vomiting 2,653,944
4 Nausea 2,198,454
5 Constipation 1,830,406
6 Rectal bleeding 1,529,450
7 Heartburn 1,473,436
8 Dyspepsia, upper abdominal pain 918,935
9 Other GI symptoms, unspecified 897,052
10 Anorectal symptoms 873,119
11 Melena 811,019
12 Abdominal distention 786,901
13 Dysphagia 766,241
14 Lower abdominal pain
751,521
15 Appetite decrease
547,817
Source: NAMCS 2002.
Estimates based on less than 30 encounters, which may be unreliable.
Infectious Causes of Gastrointestinal and Liver Disease
The CDC compiles all data from state health departments on
reportable infectious diseases via the National Notifiable Dis-
eases Surveillance System (NNDSS), a computerized system
created and monitored jointly by the CDC and the Council
of State and Territorial Epidemiologists. Once yearly, sum-
mary whole-year statistics are presented in the CDC’s Mor-
bidity and Mortality Weekly Report (MMWR). The most re-
cent summary statistics available are from 2003, and were
published online in the MMWR on April 22, 2005. This
report is available at http://www.cdc.gov/mmwr/preview/
mmwrhtml/mm5254a1.htm. Extracted from this report were
reportable infections of the gastrointestinal tract.
Mortality from Liver and Biliary Disease
Causes of death from selected liver diseases were obtained
from the U.S. Department of Health and Human Services,
the CDC, the National Center for Health Statistics, and the
Office of Analysis and Epidemiology compressed mortality
file. The compressed mortality file is a country level national
mortality and population database that spans decades and it is
derived from U.S. death certificates since 1979. A death rate
based on fewer than 20 deaths is considered unreliable. Data
are reported for deaths resulting from hepatobiliary disease
for 2002, the most recent year these data are available. These
data are available at http://wonder.cdc.gov/mortICD10J.html.
Gastrointestinal Cancer Rates
Information on cancer rates is based on data published by
the Surveillance, Epidemiology, and End Results (SEER)
Program (http://seer.cancer.gov) of the National Cancer In-
stitute (http://www.cancer.gov). The SEER program is a
GI Statistics, 2006 2131
Table 3. Leading Physician Diagnoses for Gastrointestinal Disorders in Outpatient Clinic Visits in the United States, 2002
Rank Diagnosis Estimated Visits ICD-9 Codes
1 GERD 5,512,159 530.11, 530.81
2 Abdominal pain 4,169,406 789.00, 789.09
3 Gastroenteritis 3,324,158 558.90, 008.xx, 009.xx
4 Constipation 2,562,166 564.0
5 Dyspepsia, gastritis 2,285,676 535.xx, 536.80, 536.90
6 Irritable bowel syndrome 2,063,539 564.1
7 Hemorroids 1,537,746 455.xx
8 Diverticular disease 1,493,865 562.1x
9 Hepatitis C infection 1,237,708 070.51, 070.54
10 Hernia, noninguinal 1,232,170 553.00, 553.10, 553.20, 553.90
11 Colorectal cancer 1,208,752 153.xx, 154.0, 154.1, 154.8, V10.05
12 Gallstone disease 1,109,408 574.xx, 575.0, 575.1, 575.2
13 Rectal bleeding 1,083,662 569.30
14 Hernia, inguinal 969,788 550.xx
15 Colon, benign neoplasm 853,037 211.30, 211.40
16 IBD
834,856 555.xx, 556.xx
17 GI bleed, melena
753,680 578.xx
Source: NAMCS 2002.
Estimates based on less than 30 encounters, which may be unreliable.
population-based yearly epidemiologic survey on cancer in-
cidence and survival in the United States. It provides data col-
lected and published, from 1975 on, regarding cancer preva-
lence, incidence, and mortality rates from nine population-
based cancer registries including San Francisco-Oakland
SMSA, Connecticut, Detroit (metropolitan), Hawaii, Iowa,
New Mexico, Seattle (Puget sound), Utah, and Atlanta
(metropolitan). SEER uses a “First Malignant Primary Only”
method. Therefore, the data reported include only the first
malignant tumor in a specific anatomical site (breast, colon
and rectum, stomach etc.). The reported prevalence rates for
gastrointestinal cancers include all living cases that were di-
agnosed with gastrointestinal cancer prior to 2001. Once a
case is counted, it will be included as a prevalent case for as
long as the individual is alive even if the individual had been
treated and cured (e.g., underwent a surgery and the cancer
has been excised).
Table 4. Most Common Gastrointestinal Discharge Diagnoses from Inpatient Admissions, 2002
Rank Among Rank Among Total No Median LOS Median Charges In Hospital
GI DX All DX Diagnosis (ICD-9) of Discharges (days) ($) Deaths
1 16 Chest pain NOS (786.50) 324,618 1.0 7,164 342
2 43(574.1); Cholelithiasis with ) 262,972 2.0 13,392 705
46 cholecystitis NEC 3.0 15,460 876
(574.00) (574.1)
Cholelithiasis w acute cholecystitis (574.00)
3 21 Acute pancreatitis (577.0) 243,332 4.0 11,402 3,896
4 28 Food/vomit pneumonitis 188,555 6.0 16,274 34,562
5 30 Acute appendicitis NOS (540.9) 185,550 2.0 10,759
6 31 Diverticuli of the colon w/o hemorrhage(562.11) 179,462 4.0 11,729 1,821
7 36 Noninfectious gastroenteritis NEC (558.9) 157,364 2.0 5,414 399
8 51 Gastrointestinal hemorrhage NOS (578.9) 116,724 3.0 9,514 5,957
9 57 Intestinal obstruction NOS (560.9) 102,111 4.0 8,204 2,948
10 61 Esophageal reflux (530.81) 94,919 2.0 8,060
11 80 Diverticula of the colon w hemorrhage (562.12) 74,717 3.0 9,742 1,003
12 82 Morbid obesity (278.01) 74,179 3.0 23,122 236
13 87 Intestinal adhesions w obstruction (560.81) 70,437 8.0 21,871 2,365
Too few cases to calculate a stable estimate
Special Section: Gastrointestinal Pharmacoepidemiology
and Pharmacoeconomics
Pharmaceutical data were purchased from IMS Health—
the National Prescription Audit Plus
TM
(NPA Plus
TM
). The
NPA Plus
TM
measures pharmaceutical sales from indepen-
dent and chain store pharmacies, mass merchandisers, food
stores with pharmacies, mail service pharmacies, and long-
term care facilities. Data are collected from approximately
34,000 pharmacies. Our analysis is based on a sample of
more than 20,000 randomly selected pharmacies represen-
tative of the U.S. distribution of pharmacies. All stores con-
tributed prescription drug data, but only half of the stores con-
tributed information on over-the-counter (OTC) sales; IMS
Health uses proprietary methodologies to provide National
projections.
The NPA Plus
TM
data were provided as national projec-
tions for drugs from the Uniform System of Classification
2132 Shaheen et al.
Table 5. Reported Cases of Infectious Gastrointestinal Diseases in
the United States, 2003
Salmonellosis 43,657
Giardiasis 19,709
Shigellosis 23,581
Acute hepatitis A 7,653
Acute hepatitis B 7,526
Enterohemorrhagic E. coli O157:H7 2,671
Source: Summary of Notifiable Diseases-United States, 2003. MMWR April 22,
2005;52(54):1-85. (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5254a1.htm)
(USC) classes 23410 (H2 antagonists), 23420 (proton pump
inhibitors [PPIs]), 23430 (Helicobactor pylori [H. pylori]
agents), and 23490 (other antiulcerants). The USC system
was developed in 1975 by IMS Heath, Inc., and pharmaceu-
tical manufacturers to group medical compounds by ther-
apeutic class. Projections represent the number of U.S. pre-
scriptions dispensed or OTC packages sold (in thousands) for
every available product within these USC classes (by month)
from January, 1999 through October, 2004. We aggregated
data across strengths and product formulations and created
summary estimates for each chemical entity. When applica-
ble, we aggregated across all generic products. Additionally,
we created summary estimates for each USC class to rep-
resent comparatively the types of therapeutic classes being
used in the United States.
Retail drug sales were compiled using the February
21, 2005 issue of Drug Topics (available at http://www.
drugtopics.com). Data were included from the top 200 brand
name drug, the top 200 generic drug, and the top 200 OTC
drug reports; original data were compiled by Verispan,a
health information company. In compiling data for our ta-
bles, medications with FDA-approved indications for gas-
trointestinal diseases, as well as those with no FDA approval
but common off-label usage, wereincluded. Immunosuppres-
sive agents used in liver transplant were included, while an-
tidepressants, antibiotics, and analgesics, although often used
in gastrointestinal diseases, were excluded.
Table 6. Causes of Death from Selected Liver Diseases in the United
States, 2002
Rate per # of ICD-10
100,000 Deaths Code
Liver cell carcinoma 4.9 14,047 C22
Alcoholic liver disease 4.2 12,121 K70.0-K70.4, K70.9
Acute hepatitis C 1.5 4,321 B17.1
Bile duct carcinoma 1.0 2,999 C22.1
Acute hepatitis B 0.2 659 B16, B16.0, B16.1,
B16.2, B17.0
Chronic hepatitis C 0.2 518 B18.2
Primary biliary cirrhosis 0.1 418 K74.3
Acute hepatitis A
76 B15, B15.0, B15.9
Chronic hepatitis B
103 B18, B18.1
Source: U.S. Department of Health and Human Services (US DHHS), Centers for
Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS),
Office of Analysis and Epidemiology (OAE), Compressed Mortality File (CMF),
computer tape, CDC WONDER On-line Database.
Too few cases to calculate a stable estimate.
We calculated the current distribution of acid suppres-
sant and gastroprotective compounds used by the number
of prescriptions written. Antiulcerants include non-PPI and
non-H2-receptor antagonist compounds, such as sucralfate
and misoprostol. H. pylori agents include specially packaged
combination therapies, such as Prevpac
, as well as single
compounds such as bismuth subsalicylate. Trends in the us-
age of these four groups of compounds were assessed over
the last 5 yr. Among the PPIs, several agents split market
share. The proportion of total market sales in 2004 held by
each of the branded PPIs was assessed. Finally, trends in PPI
use by brand over the last 5 yr were assessed.
Although acid suppressants and gastroprotective agents
account for the vast majority of the usage of gastrointesti-
nal agents, we also collected data on the usage of other
gastrointestinal drugs. We report the most commonly used
branded gastrointestinal agents, ranked by total dollar sales
in 2004. The parent data for this table were obtained from
http://www.drugtopics.com/drugtopics/article/articleDetail.
jsp?id=150644. Generic medications encompass a large por-
tion of total sales of gastrointestinal medications. The most
commonly used generic medications for gastrointestinal dis-
ease were ranked by total sales. These data were adapted from
http://www.drugtopics.com/drugtopics/article/articleDetail.
jsp?id=150656. Finally, total sales for OTC drug prepa-
rations for gastrointestinal and liver diseases and symp-
toms were compiled. These data were adapted from
http://www.drugtopics.com/drugtopics/article/articleDetail.
jsp?id=156502. Medications listed as “generic” include
all of those preparations that are packaged and sold by
pharmacy chains, as well as those medications bearing no
trademarked name.
RESULTS
Gastrointestinal Causes of Death
Table 1 displays the leading 20 gastrointestinal causes of
death in the United States in 2001, the most recent year for
which detailed statistics are available. Colorectal cancer con-
tinues to be the number one GI-related cause of death, with
56,887 attributed deaths. This death toll represents a slight
decrease from 2000, when 57,477 deaths were attributed to
colorectal cancer. Other notable changes in the top gastroin-
testinal causes of death include an increase in the number of
deaths from fibrosis/cirrhosis of the liver from 14,003 in 2000
to 18,283 in 2001. Additionally, the number of deaths from
esophageal cancer of all histologic types has now surpassed
the number of deaths from gastric cancer, making esophageal
cancer the number five cause of gastrointestinal deaths.
Gastrointestinal Symptoms and Diagnoses
The 2002 NAMCS received 28,738 patient record forms from
1,492 participating physiciansto approximate health-care uti-
lization patterns for the estimated 889,980,491 office visits in
GI Statistics, 2006 2133
Table 7. Prevalence and Incidence of Gastrointestinal Cancers in the United States
Rank Among Rank Among Incidence Mortality
GI Cancers All Sites Cancer Site Prevalence
Incidence
Trend
§
Mortality
Trend
§
1 3 Colon and rectum 468,964 53.7 0.8
20.8 1.8
2 21 Stomach 34,105 8.9 1.6
4.7 2.9
3 22 Pancreas 21,534 11.0 0.5 10.5 0.1
4 23 Esophagus 21,156 4.5 0.3 4.4 0.6
5 25 Liver and intrahepatic ducts 12,593 6.0 3.4
4.6 1.9
Prevalence based on the SEER registry and January 1, 2001 U.S. population estimates. These prevalences are for all ages, races/ethnicity, genders, and for diseases diagnosed
between 1996 and 2000, from nine SEER registries.
Age-adjusted incidence per 100,000 for all ages, races/ethnicity, genders, and for diseases diagnosed between 1997 and 2001.
Death rates per 100,000, based on data provided by the National Center for Health Statistics (NCHS) public use data file (http://www.cdc.gov/nchs). The data are for the whole
U.S. population between 1997 and 2001 and are age adjusted to the 2001 U.S. standard population.
§
Annual Percent Change (APC) over the time interval 19922001 for both incidence and mortality trends and for all ages, races/ethnicity, genders.
The annual percent change is significantly different from zero (p < .05).
the United States in 2002, comprising 60% women and 40%
men. Private insurance (59%), Medicare (21%), Medicaid
(7.5%), and self-pay (4.4%) accounted for the main payment
sources (Tables 2 and 3).
In the 2002 NAMCS, 4% of the patient record forms listed
gastrointestinal symptoms as the principal reason prompting
the office visit (35,124,092 of 889,980,491 visits). Results are
noted in Table 2. General abdominal pain, diarrhea, vomiting,
and nausea are the most common symptoms. If nausea and
vomiting are combined, these upper tract symptoms are sec-
ond only to abdominal pain. We also performed a subgroup
analysis limiting the providers to only those listing family
practice, internal medicine, gynecology, or pediatrics. This
analysis demonstrated no change in the rankings of the top
four symptoms. Heartburn was slightly more common in this
primary care group, ranking fifth. Unsurprisingly, the codes
for gastrointestinal bleeding were less common.
GERD has surpassed abdominal pain as the principal gas-
troenterology related provider diagnosis, as noted in Table 3.
Abdominal pain, gastroenteritis, constipation, dyspepsia, and
anorectal disorders (rectal bleeding, anorectal symptoms) fol-
low in frequency. If IBS is included, abdominal pain re-
mains the most common diagnosis. A significant increase
in hepatitis C infection was also noted, likely because of
increased national awareness among patients and providers
alike (1,237,708 vs 756,774 in 2000). Again, in subgroup
analysis limited to family practice, internal medicine, gyne-
77
21
2
0.01
PPIs H2RA Anti-Ulcerants H.
pylori
Agents
Figure 1. Usage of antiacid and gastroprotective agents by number
of prescriptions written, 2004.
cology, and pediatrics, there was no change in the rankings
of the top six diagnoses.
Hospitalization for Gastrointestinal Disorders
Table 4 displays the most common inpatient gastroenterol-
ogy and hepatology related principal diagnoses from 2002,
ranked by the number of discharges. The scope of diseases
considered to be GI related was expanded from last year’s
report, and new to the list are the following diagnoses: chest
pain NOS, food/vomit pneumonitis, and morbid obesity. The
diagnosis chest pain NOS was included because this rep-
resents nonacute myocardial infarction chest pain, and a
substantial number of these admissions were likely because
of a gastrointestinal cause. This was the leading GI-related
diagnosis.
Infectious Causes of Gastrointestinal and Liver Disease
Of note in the infectious disease trends for this year is the
continuing downward incidence of reported E. coli O157:H7.
Only 2,671 cases were reported in the United States in 2003,
from a peak of 4,744 cases in the late 1990s. U.S. Department
of Agriculture measures to decrease contamination of beef
through improved processing methods are credited for this
decrease. Hepatitis A rates are also undergoing a decline since
routine childhood immunization was recommended in 1996,
down to 7,653 cases (Table 5).
Mortality from Liver and Biliary Disease
Table 6 displays the leading causes of mortality from hep-
atobiliary disease. Compared with 1999, there has been an
increase in the number of deaths from liver cell carcinoma,
alcoholic liver disease, acute hepatitis C, and acute hepatitis
A. The greatest absolute increase in the number of deaths
occurred in liver cell carcinoma. The number of deaths from
acute hepatitis A almost doubled. This spike was due in part
to a large, virulent outbreak in Pennsylvania that occurred
from green onions contaminated during harvesting.
Gastrointestinal Cancer Rates
Table 7 displays cancer incidence and prevalence rates
from the SEER registry. Colorectal cancer continues to
2134 Shaheen et al.
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
Jan-99
Mar-99
May-99
Jul-99
Sep-99
Nov-99
Jan-00
Mar-00
May-00
Jul-00
Sep-00
Nov-00
Jan-01
Mar-01
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Mar-03
May-03
Jul-03
Sep-03
Nov-03
Jan-04
Mar-04
May-04
Jul-04
Sep-04
Time
U.S. Prescriptions (in thousands)
PROTON PUMP INHIBITORS H2 ANTAGONISTS ANTI-ULCERANTS, OTHER
H-PYLORI
AGENTS
Figure 2. Trends in usage of antiacid and gastroprotective agents over 5 yr, by total number of prescriptions.
have the highest prevalence and incidence rates among
gastrointestinal malignancies, eclipsing all other gastroin-
testinal malignancies by a factor of 10. Stomach, pancre-
atic, and esophageal cancers form the next tier of cancers.
These malignancies are impressive for their high mortality—
despite the fact that colon cancer is 20 times more com-
mon than pancreatic cancer, the mortality rate of pancre-
atic cancer per 100,000 persons is more than half that of
colon cancer. This finding suggests that, among those per-
sons who do develop pancreatic cancer, the risk of mortality
is markedly higher than those individuals developing colon
cancer. Consistent with the previous trends, both the inci-
dence and mortality trends for stomach cancer continued to
decline.
Figure 3. Usage of brand name prescription proton pump inhibitors,
2004. Numbers in graphic represent the percentage of the total mar-
ket share of proton pump inibitor market held by the medication.
Total retail sales in 2004: $10,289,381,000.
Special Section: Gastrointestinal Pharmacoepidemiology
and Pharmacoeconomics
Among the gastrointestinal medications obtained from retail
stores, mail order pharmacies, and long-term care facilities,
PPIs accounted for approximately 77% of this market, while
H2-antagonist use reflected only 21% of acid suppressant
use (Fig. 1). The number of PPI prescriptions has trended up-
wardsteadily since 1999, increasing by approximately 69,000
prescriptions per month. In October 2004, approximately
8,200,000 PPI prescriptions were sold in U.S. pharmacies.
This trend in PPI prescribing contrasts the decreasing trend
in H2 antagonist use (Fig. 2). While the number of H2 an-
tagonist prescriptions was similar to the number of PPI pre-
scriptions in early 1999, prescription and OTC transactions
have trended downward by 12,300 units per month since this
time (Tables 8–10, Figs. 3, 4).
The distribution of PPI usage for 2004 is demonstrated in
Figure 3. Currently, lansoprazole (Prevacid
, TAP Pharma-
ceutical Products Inc., Lake Forest, IL) is the most commonly
used PPI, controlling approximately 31% ofthe market. How-
ever, PPI prescribing has shifted with the changing dynamics
of this market (Fig. 4). Prior to 2001, branded omeprazole
(Prilosec
, AstraZeneca Pharmaceuticals LP, Wilmington,
DE) accounted for more than half of all PPI prescriptions.
However, since 2002, lansoprazole has led the market, av-
eraging 2,300,000 U.S. prescriptions per month. The num-
ber of brand-name omeprazole prescriptions dropped precip-
itously during 2002 and 2003, with esomeprazole (Nexium
,
AstraZeneca Pharmaceuticals LP, Wilmington, DE), panto-
prazole (Protonix
, Wyeth Pharmaceuticals Inc., Philadel-
phia, PA), and rabeprazole (Aciphex
, Eisai Co., Ltd., Tokyo,
GI Statistics, 2006 2135
0
500
1000
1500
2000
2500
3000
Jan-99
Mar-99
May-99
Jul-99
Sep-99
Nov-99
Jan-00
Mar-00
May-00
Jul-00
Sep-00
Nov-00
Jan-01
Mar-01
May-01
Jul-01
Sep-01
Nov-01
Jan-02
Mar-02
May-02
Jul-02
Sep-02
Nov-02
Jan-03
Mar-03
May-03
Jul-03
Sep-03
Nov-03
Jan-04
Mar-04
May-04
Jul-04
Sep-04
Time
U.S. Prescriptions (in thousands)
PREVACID NEXIUM PROTONIX ACIPHEX
PRILOSEC (OTC) PRILOSEC OMEPRAZOLE
Figure 4. Trends in utilization of proton pump inhibitors over 5 yr, by total number of prescriptions.
Japan) taking over the majority of this market, respectively.
Generic omeprazole was introduced to the U.S. market in
November 2002 and OTC omeprazole was introduced in
September 2003. Although generic omeprazole quickly cap-
tured a significant portion of the PPI market (nearly1,000,000
prescriptions in the second month after introduction), the in-
crease in generic sales was tempered by the introduction of
OTC omeprazole.
In 2004, PPI sales in the United States topped $10 billion;
the majority of these sales (>$9.5 billion) were for brand-
name products (Table 8, Fig. 3). Compared with other ther-
apeutic markets, PPIs as a class consistently show up near
the top of all U.S. retail drug sales. Lansoprazole and es-
omeprazole were both among the top five branded products
in terms of retail sales, ranking at number two and number
four, respectively, in 2004. Pantoprazole and esomeprazole
Table 8. Brand Name Gastrointestinal Drugs in the Top 200 Brand Name Drug List (by Sales), 2004
Generic Name Brand Name 2004 Top 200 Brand Name Rank 2004 Retail Sales Percent Change from 2003
Lansoprazole Prevacid
2 $3,197,890,000 4.8%
Esomeprazole Nexium
4 $2,963,518,000 +19.0%
Pantoprazole Protonix
11 $1,910,067,000 +26.8%
Rabeprazole Aciphex
25 $1,139,155,000 +8.8%
Ondansetron Zofran
69 $ 495,657,000 +15.9%
Mycophenolate mofetil Cellcept
81 $ 399,650,000 +15.5%
Tacrolimus Prograf
86 $ 362,051,000 +20.5%
Mesalamine Asacol
98 $ 322,219,000 +7.4%
Omeprazole Prilosec
116 $ 266,809,000 64.3%
Tegaserod Zelnorm
121 $ 251,846,000 +89.4%
Peginterferon alfa-2a Pegasys
146 $ 191,754,000 +41.3%
Ondansetron Zofran ODT
168 $ 164,910,000 +61.9%
Compiled from drug topics—Top 200 brand name drugs by retail dollars in 2004, February 21, 2005 (original source: Verispan). Source data available on the web at:
http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=150644.
showed the largest increases in sales from 2003; pantoprazole
sales increased 27% and esomeprazole sales increased 19%
(Fig. 4).
Omeprazole was both the most commonly prescribed
gastrointestinal generic compound in 2004 (Table 9) and
the most commonly purchased OTC agent (Table 10). Of
note in these data is the precipitous decline in generic
omeprazole prescriptions from the previous year. There was
a 43% decline in generic prescription omeprazole sales,
coincident with the marked increase in OTC omeprazole
usage.
DISCUSSION
Gastrointestinal diseases continue to be a source of substan-
tial morbidity and mortality for the U.S. population. Our
2136 Shaheen et al.
Table 9. Generic Prescription Gastrointestinal Drugs in the Top 200 Generic Drug List (by Sales), 2004
Generic Name 2004 Top 200 Generic Drug Rank 2004 Retail Sales Percent Change from 2003
Omeprazole 4 $811,942,000 43.0%
Ranitidine 31 $222,809,000 31.5%
Prednisone 55 $158,169,000 1.2%
Methotrexate 69 $108,845,000 7.8%
Promethazine 76 $103,877,000 +6.6%
Methylprednisolone 87 $ 91,601,000 2.7%
Famotidine 98 $ 85,774,000 25.4%
Ursodiol 113 $ 67,157,000 +0.9%
Metoclopramide 116 $ 65,533,000 4.8%
Azathioprine 117 $ 65,293,000 1.9%
Nizatidine 127 $ 56,236,000 28.6%
Hyoscyamine 139 $ 48,619,000 4.6%
Promethazine/codeine 143 $ 45,462,000 13.9%
Promethazine 149 $ 43,009,000 14.6%
6-Mercaptopurine 168 $ 35,969,000 N/A
Dicyclomine 171 $ 34,205,000 3.5%
Diphenoxylate & atropine 173 $ 33,528,000 2.8%
Cholestyramine 175 $ 32,354,000 +6.7%
Sucralfate 179 $ 31,587,000 4.9%
Prednisolone 183 $ 29,934,000 15.6%
Cyclosporine micro 187 $ 29,024,000 1.1%
Hydrocortisone 193 $ 28,608,000 +3
.6%
Cyclosporine 199 $ 26,714,000 +22.0%
Compiled from drug topics—top 200 generic drugs by retail dollars in 2004, February 21, 2005 (original source: Verispan) Source data available on the web at:
http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=150656.
report highlights several trends in the epidemiology of gas-
trointestinal disease that are worthy of mention.
Colorectal cancer continues to be the number one cause of
GI-related mortality. While SEER data demonstrate modest
decreases in both incidence and mortality rates, this cancer
dwarfs all other GI malignancies both in incidence and in
mortality rates in the United States. The high ratio of preva-
lent to incident cases, compared with other GI malignancies,
suggests that many of those contracting the disease are either
cured or living with the cancer. Unfortunately, the opposite
ratio is noted in most other GI malignancies, where high mor-
tality rates are the rule (5, 6).
The NAMCS 2002 underscores the gastroenterology dis-
ease burden in the primary care office setting. It likely under-
estimates the total burden, as few gastroenterology practices
are included in the study design. While the focus of the sur-
vey on primary care offices does not lend itself well to ex-
trapolation to gastroenterology practices, it does give a better
representation of issues confronting primary care physicians.
Specific diseases that are cared for primarily by gastroenterol-
ogists and may be underestimated include IBD and chronic
liver disease. The significant changes in visits for abdominal
pain and IBS, decreased and increased, respectively, may re-
flect the improvedunderstandingandencountercoding of IBS
in the primary care setting. The significant increase in GERD
may reflect both true disease prevalence increase and/or in-
creased awareness of GERD and PPI availability.
The increase in deaths secondary to cirrhosis deserves
mention. Some data suggest that survival for those with cir-
rhosis who do not develop hepatocellular carcinoma is ac-
tually improving, perhaps secondary to improved treatment
of chronic liver disease (7). However, this trend is countered
by increasing numbers of hepatocellular carcinomas in the
United States (8, 9). Liver cancer was mildly increased in
this year’s SEER estimates. A possible explanation for the
increase in the number of deaths from liver cell carcinoma
may be the aging population with chronic hepatitis C. This
finding is consistent with other data, and is thought to be sec-
ondary to increases in end-stage HCV infection (10). Also of
note is the relatively high number of deaths (>4,000) reported
secondary to acute hepatitis C. This observation is surprising
given that acute hepatitis C is rarely reported in the literature.
A possible explanation for this discrepancy is coding error, by
which death secondary to complications from chronic hep-
atitis C infection is noted as acute hepatitis C.
Especially notable in the data on pharmacoeconomics is
the tumultuous patterns of PPI usage. Over the last 6 yr, there
has been substantial growth in the total PPI market. Some
of this growth has likely been at the expense of a shrinking
H2-receptor antagonist market. However, the decrease in H2
blocker use is much less than the growth in the PPI market,
suggesting that the majority of the growth is not from the in-
tensification of therapy in H2 blocker users. Within the class,
individual product usage has varied dramatically over time.
While some of these fluctuations might be expected as new
products were introduced to the market, other forces are likely
at play as well. For instance, the onset of a dramatic decline
in branded Prilosec
use precedes the release of release of
both generic and OTC Prilosec
. It is likely that at least the
initial stages of this decline were precipitated by marketing
strategies used to transition patients from Prilosec to es-
omeprazole (Nexium
) use. Certainly, the opposing trends
GI Statistics, 2006 2137
Table 10. Over-The-Counter (OTC) Gastrointestinal Drugs in the Top 200 OTC List (by Sales), 2004
2004 Top 200 Brand Percent Change
Generic Name Brand Name Name Rank 2004 Retail Sales from 2003
Omeprazole Prilosec OTC
6 $242,820,500 +236.6%
Laxative tablet Generic
15 $134,895,400 +0.7%
Antacid tablet Generic
16 $126,193,000 6.4%
Famotidine Pepcid AC
32 $86,610,640 +8.4%
Ranitidine Zantac 75
43 $67,506,940 10.2%
Bismuth subsalicylate liquid Pepto-Bismol
49 $59,535,700 0.6%
Psyllium liquid/powder/oil Metamucil
52 $58,471,620 9.4%
Calcium carbonate Tums EX
57 $56,863,690 6.3%
Loperamide Imodium AD
67 $52,958,700 4.5%
Loperamide & simethicone Imodium Advanced
72 $50,445,050 +1.5%
Laxative liquid/powder/oil Generic
76 $49,476,590 6.1%
Bisacodyl Dulcolax
82 $47,613,700 +15.6%
Famotidine w antacid Pepcid Complete
89 $45,099,970 3.6%
Hemorrhoidal cream/oint/spray Preparation H
90 $43,232,340 +1.5%
Simethicone Gas X
101 $39,167,310 +5.50%
Calcium & magnesium antacid Rolaids
103 $38,561,340 +7.7%
Aspirin/sod bicarb/citric acid Alka-Seltzer
113 $36,294,130 5.2%
Magnesium hydroxide Phillips
114 $35,766,450 4.6%
Psyllium tablets Metamucil
118 $33,631,490 0.9%
Sennosides Ex Lax
126 $32,145,450 5.7%
Loperamide Generic
127 $31,985,900 3.1%
Hemorrhoidal remedy Preparation H
138 $29,191,320 2.5%
Bismuth subsalycilate Generic
145 $27,510,530 6.0%
Calcium & magnesium antacid Mylanta
151 $26,981,960 12.9%
Calcium carbonate Tums Ultra
160 $24,675,440 3.2%
Methylcellulose Citrucel
161 $24,453,380 16.5%
Bismuth subsalicylate tablets Pepto-Bismol
169 $22,002,250 +1.0%
Calcium carbonate Tums
184 $20,781,060 15.0%
Magnesium/aluminum/simeth Maalox Max
187 $20,555,060 7.9%
Natural fiber Benefiber
197 $19,636,970 +4.6%
Compiled from drug topics—top 200 generic drugs by retail dollars in 2004, April 18, 2005 (original source: Information Resources, Inc., Chicago, IL) Source data available on
the Web at: http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=156502.
“Generic” reflects the sum of all generic product sales.
of Prilosec
and Nexium
use suggest that a large portion
of new Nexium
users could be Prilosec
switches. Other
factors, such as changes in formulary patterns, are also pos-
sible. Given that Nexium
continued to increase its sales in
2004, while Prevacid
sales slightly declined, it is possible
that Nexium
will be the top-selling gastrointestinal drug on
the market in 2005.
Several limitations of the databases used to compile these
data deserve mention. Certain of these databases, including
the National Inpatient Sample, are composed of data entered
into administrative databases. The data derived from such
coding should always be viewed with the collection methods
in mind. Eventhosedatathat are not derived from such admin-
istrative databases have shortcomings. For instance, preva-
lence data from the SEER registry count any cancer survivor
as a prevalent case. Therefore, a subject who underwent a
Whipple procedure and had successful resection of a pancre-
atic cancer in 1980 would still be considered as a prevalent
case of pancreatic cancer today. While classification of such
a patient as a prevalent case is somewhat imprecise, it does
avoid the difficult question of when to consider a prevalent
case of cancer “cured.” Also, data in the National Ambula-
tory Medical Care database include only data on face-to-face
patient–physician interactions. Contacts made by telephone,
as well as contacts made outside the office (including house
calls or interactions in hospital or nursing home settings), are
not included. Finally, coding of cause of death from death
certificates may be erroneous, leading to misestimation of
mortality data.
Despite these limitations, these data provide the most com-
prehensive “snapshot” of the morbidity and mortality asso-
ciated with GI diseases. Additionally, although these data do
not account for the enormous indirect costs associated with
these diseases, they give some insight as to some of the di-
rect costs involved with caring for those with gastrointestinal
problems. These data should be useful to clinicians interested
in the impact of these diseases, and policymakers wishing ra-
tional usage of health-care resources. These data can also
serve as a “jumping-off” point for clinical researchers to ask
relevant questions suggested by the data. For instance, what
temporal changes in environmental exposures have occurred
that might account for the large increase in esophageal ade-
nocarcinomas demonstrated in these data? How do changes
in American demographics impact HCV morbidity, and how
might we best meet the challenges to our health-care system
as a result of these changes? Is our approach to the usage
of acid-suppressive therapy rational, and can costs be con-
tained without negatively impacting care? Can we explain the
2138 Shaheen et al.
extreme swingsin our usage of acid suppressive products, and
what external forces are deciding prescriber behaviors? The
current data all suggest these questions as potential avenues
for further research.
Reprint requests and correspondence: Nicholas Shaheen, M.D.,
M.P.H., CB#7080, UNC-CH, Chapel Hill, NC 27599-7080.
Received December 21, 2005; accepted March 14, 2006.
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The authors indicate no potential conflicts of interest.
    • "Clopidogrel has been associated with an increased risk of gastrointestinal (GI) bleeding [3]. Consequently, to reduce its associated risk of GI bleeding it is commonly prescribed in combination with other drugs that inhibit gastric acid production, such as proton pump inhibitors (PPIs) [4,5]. In 2006, a study by Gilard et al. raised concerns about a possible drug-drug interaction between clopidogrel and omeprazole (a PPI) that could result in a decreased efficacy of clopidogrel when taken in combination with omeprazole [6] . "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: In 2009, the FDA issued a warning that omeprazole-a proton pump inhibitor (PPI)-reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs. Methods: This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006-12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole). Results: Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty. Conclusions: The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication.
    Full-text · Article · Jan 2016
    • "Equally interestingly, it is a first-in-class proton pump inhibitor and one of the most commonly prescribed drugs internationally. In a number of countries OME is available as an over the counter drug and is used by millions of people with more than 720 million prescriptions issued within 15 years from the year of approval (Kaunitz, 2014; Raghunath et al., 2005; Shaheen et al., 2006). Given the roles of P450s in the synthesis of epoxy-fatty acids, their induction by OME could have functional consequences. "
    [Show abstract] [Hide abstract] ABSTRACT: Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100mg/kg/day, p.o., 7days), sEH inhibitor TPPU (3mg/kg/day, p.o.) and OME (100mg/kg/day, p.o., 7days)+TPPU (3mg/kg/day, p.o., last 3days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE2 was monitored. While OME treatment by itself exhibited variable effects on PGE2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME+TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study.
    Full-text · Article · Nov 2015
    • "Constipation is common worldwide, affecting all ages, with prevalence of 0.7–29.6% in children and adolescents [3] and 15–50% in the elderly [1]. In the United States, constipation is one of the top five outpatient gastrointestinal diagnoses [4], costing approximately $7,500 (US dollars) for diagnosis and treatment provision [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: Aim. The objective was to evaluate the synergistic effects of fermented rice extracts (FRe) on the laxative and probiotic properties of yoghurt in rats with loperamide-induced constipation. Methods. After constipation induction, yoghurt containing FRe (BFRe; 0.05%, 0.1%, or 1%) was administered orally once per day for 6 days. Results. Loperamide treatment caused marked decreases in fecal pellet numbers and water content discharged, as well as in the surface mucosal thickness of the colonic lumen, intestinal charcoal transit ratio, thickness, and number of mucous-producing goblet cells in the colonic mucosa, whereas it increased the remnant fecal pellet number and the mean diameter of the colonic lumen. However, this loperamide-induced constipation was ameliorated by treatment with FRe, yoghurt single formula, or 0.05%, 0.1%, or 1% BFRe (10 mL/kg). Additionally, the viable numbers of Lactobacillus in the cecal contents and feces were markedly higher than those in constipated rats. Moreover, greater probiotic and laxative effects were detected in BFRe-treated rats than in rats treated with equivalent doses of yoghurt or FRe single formula. Conclusion. The results suggest that addition of FRe to liquid yoghurt will enhance the probiotic and beneficial laxative effects of yoghurt in the digestive tract, without causing side effects.
    Full-text · Article · Aug 2014
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