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le 01/09/00  |
The Effect of Ursodeoxycholic Acid Therapy on Liver Fibrosis
Progression in Primary Biliary Cirrhosis (·Human
Study·)
Christophe Corpechot, Fabrice Carrat, Anne-Marie Bonnand, Renée
Eugénie Poupon, and Raoul Poupon
Hepatology 2000 32: 1196-1199. [Abstract]
Chronic Liver Disease
Increased Hepatic Iron and Cirrhosis: No Evidence For an
Adverse Effect on Patient Outcome Following Liver Transplantation
(·Human Study·)
Katherine A. Stuart, Linda M. Fletcher, Andrew D. Clouston, Steve
V. Lynch, David M. Purdie, Paul Kerlin, and Darrell H. G. Crawford
Hepatology 2000 32: 1200-1207. [Abstract]
Bioelectrical Impedance Analysis Is a Useful Bedside Technique
to Assess Malnutrition in Cirrhotic Patients With and Without
Ascites (·Human Study·)
Matthias Pirlich, Tatjana Schütz, Theo Spachos, Siegfried
Ertl, Marie-Luise Weiß, Herbert Lochs, and Mathias Plauth
Hepatology 2000 32: 1208-1215. [Abstract]
Growth Regulation and Cancer
Risk Factors for Recurring Hepatocellular Carcinoma Differ
According to Infected Hepatitis VirusAn Analysis of 236 Consecutive
Patients With a Single Lesion (·Human Study·)
Yukihiro Koike, Yasushi Shiratori, Shinpei Sato, Shuntaro Obi,
Takuma Teratani, Masatoshi Imamura, Keisuke Hamamura, Yasuo Imai,
Haruhiko Yoshida, Shuichiro Shiina, and Masao Omata
Hepatology 2000 32: 1216-1223. [Abstract]
Results of Surgical and Nonsurgical Treatment for Small-Sized
Hepatocellular Carcinomas: A Retrospective and Nationwide Survey
in Japan (·Human Study·)
Shigeki Arii, Yoshio Yamaoka, Syunji Futagawa, Kyoichi Inoue,
Kenichi Kobayashi, Masamichi Kojiro, Masatoshi Makuuchi, Yasuni
Nakamura, Kiwamu Okita, and Ryusaku Yamada
Hepatology 2000 32: 1224-1229. [Abstract]
Flow-Cytometric Separation and Enrichment of Hepatic Progenitor
Cells in the Developing Mouse Liver
Atsushi Suzuki, Yun-wen Zheng, Reika Kondo, Moriaki Kusakabe,
Yasutsugu Takada, Katashi Fukao, Hiromitsu Nakauchi, and Hideki
Taniguchi
Hepatology 2000 32: 1230-1239. [Abstract]
Inflammation, Cytokines, and Fibrosis
Fibrous Obliterative Lesions of Veins Contribute to Progressive
Fibrosis in Chronic Liver Allograft Rejection (·Human
Study·)
Yuichi Nakazawa, Julie R. Jonsson, Neal I. Walker, Paul Kerlin,
Charles Steadman, Stephen V. Lynch, Russell W. Strong, and Andrew
D. Clouston
Hepatology 2000 32: 1240-1247. [Abstract]
Tissue Inhibitor of Metalloproteinases-1 Promotes Liver
Fibrosis Development in a Transgenic Mouse Model
Hitoshi Yoshiji, Shigeki Kuriyama, Yoji Miyamoto, Unnur P. Thorgeirsson,
Daniel E. Gomez, Mitsuhiro Kawata, Junichi Yoshii, Yasuhide Ikenaka,
Ryuichi Noguchi, Hirohisa Tsujinoue, Toshiya Nakatani, Snorri
S. Thorgeirsson, and Hiroshi Fukui
Hepatology 2000 32: 1248-1254.
[Abstract]
Liver Cell Injury and Apoptosis
Gene Delivery of Cu/Zn-Superoxide Dismutase Improves Graft
Function After Transplantation of Fatty Livers in the Rat
Thorsten G. Lehmann, Michael D. Wheeler, Robert F. Schwabe, Henry
D. Connor, Robert Schoonhoven, Hartwig Bunzendahl, David A. Brenner,
R. Jude Samulski, Zhi Zhong, and Ronald G. Thurman
Hepatology 2000 32: 1255-1264. [Abstract]
Chronic Graft-Versus-Host Disease of the Liver: Presentation
as an Acute Hepatitis (·Human Study·)
Simone I. Strasser, Howard M. Shulman, Mary E. Flowers, Rajender
Reddy, David A. Margolis, Manfred Prumbaum, Stuart E. Seropian,
and George B. McDonald
Hepatology 2000 32: 1265-1271. [Abstract]
Tumor Necrosis Factor Prevents Tumor Necrosis Factor Receptor-Mediated
Mouse Hepatocyte Apoptosis, But Not Fas-Mediated Apoptosis: Role
of Nuclear Factor-B
Masahito Nagaki, Takafumi Naiki, David A. Brenner, Yosuke Osawa,
Motoaki Imose, Hideki Hayashi, Yoshiko Banno, Shigeru Nakashima,
and Hisataka Moriwaki
Hepatology 2000 32: 1272-1279. [Abstract]
Mechanisms of Ischemic Injury Are Different in the Steatotic
and Normal Rat Liver
Markus Selzner, Hannes A. Rüdiger, David Sindram, John Madden,
and Pierre-Alain Clavien
Hepatology 2000 32: 1280-1288. [Abstract]
Endotoxin-Induced Mortality in Bile Duct-Ligated Rats After
Administration of Reconstituted High-Density Lipoprotein
Miguel E. Sewnath, Han H. M. Levels, Ronald Oude Elferink, Cornelis
J. F. van Noorden, Fiebo J. W. ten Kate, Sander J. H. van Deventer,
and Dirk J. Gouma
Hepatology 2000 32: 1289-1299. [Abstract]
Design of a Temporally and Spatially Controlled Drug Delivery
System for the Treatment of Liver Diseases in Mice
Isao Shibuya, Toshihiro Akaike, and Yoshifumi Watanabe
Hepatology 2000 32: 1300-1308. [Abstract]
Metabolism, Transport, and Genetic Diseases
Induction of Bile Acid Synthesis by Cholesterol and Cholestyramine
Feeding Is Unimpaired in Mice Deficient in Apolipoprotein AI
Christopher D. Jolley, John M. Dietschy, and Stephen D. Turley
Hepatology 2000 32: 1309-1316.
[Abstract]
Impaired Protein Maturation of the Conjugate Export Pump
Multidrug Resistance Protein 2 as a Consequence of a Deletion
Mutation in Dubin-Johnson Syndrome (·Human
Study·)
Verena Keitel, Jürgen Kartenbeck, Anne T. Nies, Herbert Spring,
Manuela Brom, and Dietrich Keppler
Hepatology 2000 32: 1317-1328. [Abstract]
High Prevalence of the Very Rare Wilson Disease Gene Mutation
Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain):
A Genetic and Clinical Study (·Human Study·)
Luis García-Villarreal, Susan Daniels, Sarah H. Shaw, David
Cotton, Margaret Galvin, Jeanne Geskes, Paula Bauer, Angel Sierra-Hernández,
Alan Buckler, and Antonio Tugores
Hepatology 2000 32: 1329-1336. [Abstract]
A Missense Mutation in FIC1 Is Associated With
Greenland Familial Cholestasis (·Human
Study·)
Leo W. J. Klomp, Laura N. Bull, Alexander S. Knisely, Marjolein
A. M. van der Doelen, Jenneke A. Juijn, Ruud Berger, Sylviane
Forget, Inge-Merete Nielsen, Hans Eiberg, and Roderick H. J. Houwen
Hepatology 2000 32: 1337-1341. [Abstract]
Control by Signaling Modulators of the Sorting of Canalicular
Transporters in Rat Hepatocyte Couplets: Role of the Cytoskeleton
Marcelo G. Roma, Piotr Milkiewicz, Elwyn Elias, and Roger Coleman
Hepatology 2000 32: 1342-1356.
[Abstract]
Molecular Cell Biology
Effect of Cholera Toxin and Cyclic Adenosine Monophosphate
on Fluid-Phase Endocytosis, Distribution, and Trafficking of Endosomes
in Rat Liver
Rebecca W. Van Dyke
Hepatology 2000 32: 1357-1369. [Abstract]
Retroviral Gene Transfer of Signaling Molecules Into Murine
Fetal Hepatocytes Defines Distinct Roles for the STAT3 and Ras
Pathways During Hepatic Development
Yoshiaki Ito, Takaaki Matsui, Akihide Kamiya, Taisei Kinoshita,
and Atsushi Miyajima
Hepatology 2000 32: 1370-1376. [Abstract]
The Promoter of the Long Variant of Collagen XVIII, the
Precursor of Endostatin, Contains Liver-Specific Regulatory Elements
(·Human Study·)
Jocelyne Liétard, Nathalie Théret, Marko Rehn, Orlando
Musso, Delphine Dargère, Taina Pihlajaniemi, and Bruno
Clément
Hepatology 2000 32: 1377-1385. [Abstract]
Viral Hepatitis
Mutations in the E2-PePHD and NS5A Region of Hepatitis C
Virus Type 1 and the Dynamics of Hepatitis C Viremia Decline During
Interferon Alfa Treatment (·Human Study·)
Thomas Berg, Andreas Mas Marques, Marina Höhne, Bertram Wiedenmann,
Uwe Hopf, and Eckart Schreier
Hepatology 2000 32: 1386-1395. [Abstract]
RAPID COMMUNICATION:
A Randomized Trial Comparing Wireless Capsule Endoscopy
With Push Enteroscopy for the Detection of Small-Bowel Lesions
MARK APPLEYARD, ZVI FIREMAN, ARKADY GLUKHOVSKY, HAROLD JACOB,
REUVEN SHREIVER, SRINATHAN KADIRKAMANATHAN, ALEXANDRA LAVY, SCHLOMO
LEWKOWICZ, EYTAN SCAPA, RONA SHOFTI, PAUL SWAIN, and ASSAF ZARETSKY
Gastroenterology 2000 119: 1431-1438. Published online Nov 29
2000. [Abstract]
ALIMENTARY TRACT:
Excess Gastroesophageal Reflux in Patients With Hiatus Hernia
Is Caused by Mechanisms Other Than Transient LES Relaxations
MARGOT A. VAN HERWAARDEN, MELVIN SAMSOM, and ANDRÉ J. P.
M. SMOUT
Gastroenterology 2000 119: 1439-1446. Published online Dec 11
2000. [Abstract]
Very High Risk of Cancer in Familial Peutz-Jeghers Syndrome
FRANCIS M. GIARDIELLO, JILL D. BRENSINGER, ANNE C. TERSMETTE,
STEVEN N. GOODMAN, GLORIA M. PETERSEN, SUSAN V. BOOKER, MARCIA
CRUZ-CORREA, and JOHAN A. OFFERHAUS
Gastroenterology 2000 119: 1447-1453. Published online Dec 11
2000. [Abstract]
Ileorectal Anastomosis Is Appropriate for a Subset of Patients
With Familial Adenomatous Polyposis
CHARLOTTE BÜLOW, HANS VASEN, HEIKKI JÄRVINEN, JAN BJÖRK,
MARIE LUISE BISGAARD, and STEFFEN BÜLOW
Gastroenterology 2000 119: 1454-1460. Published online Dec 11
2000. [Abstract]
Safety and Efficacy of Recombinant Human Interleukin 10
in Chronic Active Crohn's Disease
STEFAN SCHREIBER, RICHARD N. FEDORAK, OLE HAAGEN NIELSEN, GARY
WILD, C. NOEL WILLIAMS, SUSANNA NIKOLAUS, MERON JACYNA, BRET A.
LASHNER, ALFRED GANGL, PAUL RUTGEERTS, KIM ISAACS, SANDER J. H.
VAN DEVENTER, JACOB C. KONINGSBERGER, MARIELLE COHARD, ALESANDRE
LeBEAUT, STEPHEN B. HANAUER, and THE CROHN'S DISEASE IL-10 COOPERATIVE
STUDY GROUP
Gastroenterology 2000 119: 1461-1472. Published online Dec 11
2000. [Abstract]
Recombinant Human Interleukin 10 in the Treatment of Patients
With Mild to Moderately Active Crohn's Disease
RICHARD N. FEDORAK, ALFRED GANGL, CHARLES O. ELSON, PAUL RUTGEERTS,
STEFAN SCHREIBER, GARY WILD, STEPHEN B. HANAUER, ANN KILIAN, MARIELLE
COHARD, ALEXANDRE LeBEAUT, BRIAN FEAGAN, and THE INTERLEUKIN 10
INFLAMMATORY BOWEL DISEASE COOPERATIVE STUDY GROUP
Gastroenterology 2000 119: 1473-1482. Published online Dec 11
2000. [Abstract]
Linkage Heterogeneity for the IBD1 Locus in Crohn's
Disease Pedigrees by Disease Onset and Severity
STEVEN R. BRANT, CAROLIEN I. M. PANHUYSEN, JOAN E. BAILEY-WILSON,
PATRICK M. ROHAL, SINDA LEE, JASDEEP MANN, GEOFFREY RAVENHILL,
BARBARA S. KIRSCHNER, STEPHEN B. HANAUER, JUDY H. CHO, and THEODORE
M. BAYLESS
Gastroenterology 2000 119: 1483-1490. Published online Dec 11
2000. [Abstract]
Susceptibility to Severe Ulcerative Colitis Is Associated
With Polymorphism in the Central MHC Gene IKBL
EMILIO G. DE LA CONCHA, MIGUEL FERNANDEZ-ARQUERO, GONTRAND LOPEZ-NAVA,
ESTER MARTIN, RICHARD J. ALLCOCK, LAURA CONEJERO, JULIO GARCIA
PAREDES, and MANUEL DIAZ-RUBIO
Gastroenterology 2000 119: 1491-1495. Published online Dec 11
2000. [Abstract]
Postabsorptive Plasma Citrulline Concentration Is a Marker
of Absorptive Enterocyte Mass and Intestinal Failure in Humans
PASCAL CRENN, COLETTE COUDRAY-LUCAS, FRANCOIS THUILLIER, LUC CYNOBER,
and BERNARD MESSING
Gastroenterology 2000 119: 1496-1505. Published online Dec 11
2000. [Abstract]
Congenital Sodium Diarrhea Is an Autosomal Recessive Disorder
of Sodium/Proton Exchange but Unrelated to Known Candidate Genes
THOMAS MÜLLER, CISCA WIJMENGA, ALAN D. PHILLIPS, ANDREAS
JANECKE, RODERICK H. J. HOUWEN, HELMUT FISCHER, HELMUT ELLEMUNTER,
MARTIN FRÜHWIRTH, FELIX OFFNER, SABINE HOFER, WILFRIED MÜLLER,
IAN W. BOOTH, and PETER HEINZ-ERIAN
Gastroenterology 2000 119: 1506-1513. Published online Dec 11
2000. [Abstract]
Interleukin 18 Is a Potent Proliferative Factor for Intestinal
Mucosal Lymphocytes in Crohn's Disease
TAKANORI KANAI, MAMORU WATANABE, AKIRA OKAZAWA, KOICHI NAKAMARU,
MAKIYO OKAMOTO, MAKOTO NAGANUMA, HIROMASA ISHII, MASAO IKEDA,
MASASHI KURIMOTO, and TOSHIFUMI HIBI
Gastroenterology 2000 119: 1514-1523. Published online Dec 11
2000. [Abstract]
Modulation of Barrier Function During Fas-Mediated Apoptosis
in Human Intestinal Epithelial Cells
MARIA T. ABREU, ANDREW A. PALLADINO, ELIZABETH T. ARNOLD, RICHARD
S. KWON, and JAMES A. McROBERTS
Gastroenterology 2000 119: 1524-1536. Published online Dec 11
2000. [Abstract]
Drug Enterocyte Adducts: Possible Causal Factor for Diclofenac
Enteropathy in Rats
CHESSLEY R. ATCHISON, A. BRIAN WEST, ARUN BALAKUMARAN, SALLY J.
HARGUS, LANCE R. POHL, DAVIS H. DAIKER, JUDITH F. ARONSON, WALTER
E. HOFFMANN, BRYAN K. SHIPP, and MARY TREINEN-MOSLEN
Gastroenterology 2000 119: 1537-1547. Published online Dec 11
2000. [Abstract]
Uptake and Presentation of Antigen to T Cells by Primary
Colonic Epithelial Cells in Normal and Diseased States
GRZEGORZ W. TELEGA, DANIEL C. BAUMGART, and SIMON R. CARDING
Gastroenterology 2000 119: 1548-1559. Published online Dec 11
2000. [Abstract]
Adrenal Cortical Activation in Murine Colitis
DENIS FRANCHIMONT, GERD BOUMA, JEROME GALON, GERNOT W. WOLKERSDÖRFER,
ANDREA HAIDAN, GEORGE P. CHROUSOS, and STEFAN R. BORNSTEIN
Gastroenterology 2000 119: 1560-1568. Published online Dec 11
2000.
[Abstract]
Peripheral Corticotropin-Releasing Factor and Stress-Stimulated
Colonic Motor Activity Involve Type 1 Receptor in Rats
CÉLINE MAILLOT, MULUGETA MILLION, JEN YU WEI, ARIANE GAUTHIER,
and YVETTE TACHÉ
Gastroenterology 2000 119: 1569-1579. Published online Dec 11
2000. [Abstract]
Prostaglandin EP Receptor Subtypes Have Distinctive Effects
on Jejunal Afferent Sensitivity in the Rat
WOLFRAM HAUPT, WEN JIANG, MARTIN E. KREIS, and DAVID GRUNDY
Gastroenterology 2000 119: 1580-1589. Published online Dec 11
2000. [Abstract]
Interstitial Cells of Cajal and Inflammation-Induced Motor
Dysfunction in the Mouse Small Intestine
TARA DER, PREMYSL BERCIK, GRAEME DONNELLY, TIM JACKSON, IRENE
BEREZIN, STEPHEN M. COLLINS, and JAN D. HUIZINGA
Gastroenterology 2000 119: 1590-1599. Published online Dec 11
2000. [Abstract]
Lower Esophageal Sphincter Relaxation and Activation of
Medullary Neurons by Subdiaphragmatic Vagal Stimulation in the
Mouse
Q. SANG and RAJ K. GOYAL
Gastroenterology 2000 119: 1600-1609. Published online Dec 11
2000.
[Abstract]
Neutrophil Chemoattractant 2 Regulates Expression of the
Reg Gene in Injured Gastric Mucosa in Rats
HIDEAKI KAZUMORI, SHUNJI ISHIHARA, EIICHI HOSHINO, KOUSAKU KAWASHIMA,
NOBUYUKI MORIYAMA, HIROSHI SUETSUGU, HIROSHI SATO, KYOICHI ADACHI,
RYO FUKUDA, MAKOTO WATANABE, SHIN TAKASAWA, HIROSHI OKAMOTO, HIROKAZU
FUKUI, TSUTOMU CHIBA, and YOSHIKAZU KINOSHITA
Gastroenterology 2000 119: 1610-1622. Published online Dec 11
2000. [Abstract]
Civilisation and the colon: constipation as the "disease
of diseases"
James Whorton BMJ 2000;321 1586-1589. (Full
text)
Drug for irritable bowel syndrome taken off the market Fred Charatan, Florida (Full text)
ABC of colorectal cancer: Innovative treatment for colon
cancer
G A Chung-Faye and D J Kerr
BMJ 2000; 321: 1397-1399.
[Full text]
Brief Report: Transmission of Hepatitis C Virus from a Patient
to an Anesthesiology Assistant to Five Patients
R. Stefan Ross, Sergei Viazov, Tanja Gross, Friedrich Hofmann,
Hans-Martin Seipp, Michael Roggendorf (Abstract)
Peginterferon Alfa-2a in Patients with Chronic Hepatitis
C
Stefan Zeuzem, S. Victor Feinman, Jens Rasenack, E. Jenny Heathcote,
Ming-Yang Lai, Edward Gane, John O'Grady, Jurg Reichen, Moises
Diago, Amy Lin, Joseph Hoffman, Michael J. Brunda (Abstract)
Peginterferon Alfa-2a in Patients with Chronic Hepatitis
C and Cirrhosis
E. Jenny Heathcote, Mitchell L. Shiffman, W. Graham E. Cooksley,
Geoffrey M. Dusheiko, Samuel S. Lee, Luis Balart, Robert Reindollar,
Rajender K. Reddy, Teresa L. Wright, Amy Lin, Joseph Hoffman,
Jean De Pamphilis (Abstract)
Correspondence
Comparison of Colonoscopy and Double-Contrast Barium Enema (Abstract)
The Effect of Fecal Occult-Blood Screening on the Incidence
of Colorectal Cancer
Jack S. Mandel, Timothy R. Church, John H. Bond, Fred Ederer,
Mindy S. Geisser, Steven J. Mongin, Dale C. Snover, Leonard M.
Schuman (Abstract)
The Best Screening Test for Colorectal Cancer -- A Personal Choice EDITORIAL (Full text)
Screening for Colorectal Cancer CORRESPONDANCE
(Full
Text)
Hepatic Iron Concentration and Total Body Iron Stores in
Thalassemia Major CORRESPONDANCE (Full
Text)
Serological diagnosis of inflammatory bowel disease
*Paul Rutgeerts, Séverine Vermeire [Abstract]
Pain after stapled haemorrhoidectomy
*Johannes H P M Jongen, Jens-Uwe Bock [Full
Text]
Jejunal ulceration and push enteroscopy
*Andrew C F Taylor, Rosamund M Allen, Raymond J Buttigieg [Full
Text]
Add colorectal cancer to list of smoking-associated cancers,
say experts
Jane Bradbury [Full
Text]
Barrett's metaplasia
Janusz A Jankowski, Rebecca F Harrison, Ian Perry, Fran Balkwill,
Chris Tselepis [Abstract]
Clostridium difficile, disinfectant, and elemental
diet
Hiroaki Itou, *Masahiro Iizuka, Junichi Chihara, Masako Tobita,
Sumio Watanabe
[Full Text]
European resorts at risk of Legionella
Bénédicte Decludt, *Jerome Etienne [Full
Text]
Upper-gastrointestinal haemorrhage managed without endoscopy
*Peter Trewby [Full
Text]
Cost effectiveness of initial endoscopy 'Initial endoscopy in dyspeptic patients might be a cost-effective intervention'
Evidence of cost effectiveness is required to justify initial endoscopy for patients with dyspepsia because this procedure is expensive relative to empirical prescribing. B Delaney and colleagues did a randomised controlled trial to establish the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years. Symptoms, cost effectiveness, and patient satisfaction and quality of life were assessed. Initial endoscopy resulted in improved symptoms and quality of life. The incremental cost-effectiveness ratio was very sensitive to the cost of endoscopy. Researchers concluded that provided the unit cost of endoscopy can be limited to £100, initial endoscopy might be cost effective.
Cost effectiveness of initial endoscopy for dyspepsia in
patients over age 50 years: a randomised controlled trial in primary
care
B C Delaney, S Wilson, A Roalfe, L Roberts, V Redman, A Wearn,
A Briggs, F D R Hobbs
Department of Primary Care and General Practice, University
of Birmingham, Medical School, Edgbaston, Birmingham B15 2TT,
UK (B C Delaney MD, S Wilson PhD, A Roalfe MSc, Prof L Roberts
BSc, V Redman, A Wearn MRCGP, Prof F D R Hobbs FRCGP);
and Health Economics Research Centre, University of Oxford, Institute
of Health Sciences, Headington, Oxford (A Briggs DPhil)
Correspondence to: Dr B C Delaney (e-mail:b.c.delaney@bham.ac.uk)
Summary
Background Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings, or by empirical prescribing. We aimed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician.
Methods 422 patients were recruited and randomly assigned to initial endoscopy or usual management. Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness. Secondary outcomes were quality of life and patient satisfaction. Total costs were calculated from individual patient's use of resources with unit costs applied from national data. Statistical analysis of uncertainty on incremental cost-effectiveness ratio (ICER) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves.
Findings In the 12 months following recruitment, 213 (84%) patients had an endoscopy compared with 75 (41%) controls. Initial endoscopy resulted in a significant improvement in symptom score (p=0·03), and quality of life pain dimension (p=0·03), and a 48% reduction in the use of proton pump inhibitors (p=0·005). The ICER was £1728 (UK£) per patient symptom-free at 12 months. The ICER was very sensitive to the cost of endoscopy, and could be reduced to £165 if the unit cost of this procedure fell from £246 to £100.
Interpretation Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention.
Lancet 2000; 356: 1965-69
Correspondence
Alosetron for irritable bowel syndrome
*Elizabeth Barbehenn, Peter Lurie, Sidney M Wolfe
Sir--Michael Camilleri and colleagues (March
25, p 1035)1 report that alosetron is an effective treatment for
irritable bowel syndrome (IBS). However, the US Food and Drug
Administration (FDA) Medical Officer's Review (now available at
www.fda.gov/cder/approval/index.htm
accessed on Nov 12, 2000), which we originally obtained through
the US Freedom of Information Act, has led us to question some
of the analyses presented in the article.
The graphic techniques used by Camilleri and colleagues greatly exaggerate alosetron's efficacy. Their figure 3 presents the relative difference in pain and discomfort scores from baseline on a 0-4 scale for the treated and placebo groups. Presented this way, the drug seems effective. However, when we plotted the absolute data contained in the Medical Officer's Review, the data points are almost superimposable (figure). The exclusion of the baseline data from Camilleri and colleagues' figure 3, unusual in a graph of this type, has the additional effect of enlarging the Y axis, and creating an apparent greater benefit for the drug.
http://image.thelancet.com/lancet/issues/vol356no9246/correspondence2009/00cor9049.gifðð
Trend in absolute pain and discomfort scores
The important finding that efficacy was confined to diarrhoea-predominant patients and was not evident among patients who alternated between diarrhoea and constipation (alternators) is relegated to a single sentence in the results. The FDA used this subgroup analysis as the basis for denying approval of the drug for use in alternators. Instead, Camilleri and colleagues concentrate overwhelmingly on the marginal benefits of the drug in the full study population, which they describe in their report's title as IBS patients, obscuring the fact that they provide no evidence of benefit on the primary outcome variable in constipation-predominant patients (who were excluded) or alternators. This form of data presentation could lead to overprescribing. Moreover, whether the diarrhoea-predominant patients even had diarrhoea is unclear. The medical officer reviewing the study stated: "Patients considered by investigators to fit the diarrhea-predominant subtype had at baseline . . . stool consistency values that were neither loose nor watery". The Medical Officer's Review is dated Nov 4, 1999, well before Camilleri and colleagues' report went to press. Since five of the six investigators are employees of the pharmaceutical company that generated these data, the Medical Officer's Review should have come to their attention in time to be incorporated into the final draft of the report. These discrepancies raise important questions about data presentation in studies sponsored by pharmaceutical companies.
*Elizabeth Barbehenn, Peter Lurie, Sidney M Wolfe
------------------------------------------------------------------------
Public Citizen's Health Research Group, 1600 20th Street NW, Washington,
DC 20009, USA
1 Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000; 355: 1035-40. [Text]
Author's reply
Sir--Alosetron is the first and only agent which has been shown in large, randomised, placebo-controlled, replicate studies to produce improvement in multiple symptoms of IBS. The Food and Drug Administration medical team leader, in his review of the alosetron new drug application1 clearly made the point that "These efficacy results are very convincing because, up to now, drugs tested for efficacy in IBS have shown inconsistent results. In no other instance have replicate data like those observed with alosetron been reported."
IBS is a multidimensional disease and alosetron produces benefit for many relevant endpoints, including adequate relief of pain and discomfort, reduction in stool frequency, improvement in consistency, and reduction in days with urgency. Pain-score data were also collected. We presented the pain score data percentage change from baseline. Such presentation is standard and accepted in peer-reviewed scientific journals. It would have been inappropriate to plot the values as the actual mean pain scores as the principal analysis was change from baseline. We included baseline pain-score data in our table 1 and calculation of the absolute numbers from the percentages can be done easily. Since patients' baseline pain scores were around 2·0, there is not justification to draw the graph with the Y axis ranging from 0-4 just because the scale for pain covered that range.
We clearly stated that benefit was seen in diarrhoea-predominant patients, but not in alternators, compared with placebo.
The new drug application for alosetron was submitted for women with diarrhoea-predominant IBS; this information is available. The assertion that over prescribing might occur based on our use of the term IBS in the title is without foundation.
We disagree that it is unclear whether the diarrhoea-predominant patients even had diarrhoea. Stratification of patients into IBS subtype was done independently by the enrolling physician on the basis of the patient's predominant bowel pattern during at least 6 months before entry to the study, and this is clearly stated. This stratification was independent of stool-consistency scores collected in the 2-week screening period, which was too short to diagnose diarrhoea-predominant IBS according to the Rome criteria, but was useful to avoid inclusion of patients who were constipated at study entry. Additionally, there is no definition of diarrhoea that is widely accepted on the basis of stool consistency.
The date of the Medical Officer's Review referred to by Barbehenn and colleagues is misleading. Alosetron was approved by the Food and Drug Administration on Feb 9, 2000, not in November, 1999. As a matter of procedure, requests for the reviews cannot be honoured until after a drug is approved. We did request, by the Freedom of Information Act, the Medical Officer's Review in February, 2000, but did not receive information until June, 2000. Irrespective of the timelines, we do not necessarily agree with all of the conclusions reached in those reviews and do not believe that these would have led us to change our report.
Allen W Mangel
------------------------------------------------------------------------
Glaxo Wellcome, 5 Moore Drive, Research Triangle Park, NC 27709,
USA (e-mail:awm43512@glaxowellcome.com)
1 Medical Team Leader Review 1999.
Why should hepatitis C affect immune reconstitution in HIV-1-infected
patients?
Camilla S Graham, *Margaret James Koziel
December 13 2000 Vol. 284 No. 22
Alcohol and Substance Abuse Among Medical Residents
J. Mitchell Simson; David C. Yao; Scott M. Wright (FULL
TEXT )
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