Review for 10.1186/1471-230X-9-25 (2009)

Reviewer's report
Title:Decreasing Incidence of Peptic Ulcer Complications Despite Increasing
Sales of Prescribed NSAID:s, a study of the Swedish Population from
1974-2002.
Version: 1Date:24 January 2008
Reviewer: Henrik Sorensen
Reviewer's report:
This study covers an important public health/clinical issue, namely the
development of the incidence of peptic ulcer complications over a long time
period. The authors have access to a unique dataset, that is, the Swedish
National Hospital Discharge Register. Ulcus complications have a high mortality
and it is therefore important to understand the epidemiology of this disease in
order to investigate if complications can be prevented. The past decades have
furthermore seen a change in the incidence of the most frequent risk factors for
developing peptic ulcer disease which makes the problem particularly interesting.
However, in the present form this paper has a lot of limitations.
1. There are uncertainties about the aim, which in the abstract is described as
â##to investigate the incidence of complications before and after introduction of
H2-blockers and proton pump inhibitors and compare it with the sales of
ASA/NSAIDsâ##. In Background, the authors state already in the first paragraph
that â##the first aim of this study was to investigate whether the results from our
first study from the south of Sweden are valid for the entire countryâ##.
2. The authors need to be clearly state the problem they intend to solve and be
crystal clear in formulating the problem.
3. The second paragraph in Background seems a bit detached from its content.
There is no doubt that the Swedish registry is of high quality, but it is not relevant
to state so here.
4. The review of the existing literature is not complete. For instance, a similar
Danish study has shown the same results, that is, declining rates for bleeding
and perforated ulcus. Please see Christensen et al. Introduction of newer
selective cyclo-oxygenase-2 inhibitors and rates of hospitalization with bleeding
and perforated peptic ulcer. Aliment Pharmacol Ther. 2007;25:907-12.
5. The Method section could be structurally improved by some inserting some
headings. The reader needs to know the size of the Swedish population as well
as the structure of the Swedish health system. To a Scandinavian reader this is
evident, but it may not be to an international readership. The above-mentioned
2nd paragraph in the Background section could be moved to the Methods
section.
6. As far as I understand, the authors have used indirect standardization in the
statistical analysis. It is unclear why 1995 was chosen as external reference. This
indirect standardization causes for instance the problem that the results cannot
be extrapolated to international populations.
7. It is also unclear why the authors have chosen a linear regression analysis and
whether the data indeed fulfil the criteria for a regression analysis.
8. The authors have chosen to collect aggregated information on use of
ASA/NSAID. Why did they not collect information on selective Cox-2 inhibitors?
9. Generally the authors list incidence rates as well as P-values, which can be
called statistically significant merely due to the size of the data material. From an
epidemiological, and a clinical, point of view 95% confidence intervals for the risk
estimates would be more interesting to know.
10. The authors do not quantify the impact of potential bias on the risk estimates,
for example caused by misclassification of the diagnosis.
11. Which age categories did the authors use?
12. Also the Discussion section could be improved structurally. The studyâ##s
main conclusion should be listed initially. Hereafter the authors need to
thoroughly discuss their own results in comparison with the existing literature.
13. Next, the authors should discuss the various ways of interpreting the results.
The present discussion touches on a number of factors, such as tobacco use,
alcohol consumption and exposure to Helicobacter pylori infections. There must
be aggregated data in the Swedish population on how smoking, alcohol
consumption and use of antibiotics for Helicobacter pylori have developed during
the same period of time.
14. Since this is an ecologic study, there is naturally a considerable risk of
ecological fallacy. Please see Morgenstern H. Uses of ecologic analysis in
epidemiologic research. Am J Public Health. 1982;72:1336-44. The authors need
to discuss this issue in details. A number of the studies mentioned in the paper
as potential explanations for the authorsâ## findings are relevant, though not
sufficiently exhaustive. For instance the authors do not discuss NSAIDs as a risk
factor nor the introduction of Cox-2 inhibitors at the end of 1990s. The literature
search for 5 ASA and NSAID, respectively, as risk factor for ulcus complications
is not exhaustive. Please see Nielsen et al. Risk of hospitalization resulting from
upper gastrointestinal bleeding among patients taking corticosteroids: a
register-based cohort study. Am J Med. 2001;111:541-5, and SÃ¸rensen et al.
Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin.
Am J Gastroenterol. 2000;95:2218-24.
These are studies familiar to me but there are other international examples.
15. The references are a bit of a mess. For instance, in the Methods section the
authors refer to a Swedish study from 1994 â## reference 33. The study is in fact
reference 14, or so I suppose. Some references list volume numbers, some do
not. In reference 23, the author names are underlined.
Minor comments
1. The abstract does not contain information on when H2-blockers and proton
pump inhibitors were introduced on the Swedish market.
2. Nor does it have any information on the incidence rates.
3. The conclusion in the abstract is not a conclusion but merely a summary of the
results.
4. The authors make several statements which are not followed by a reference,
e.g. the third sentence in the Discussion section: â#¦. Several authors reportâ#¦.
is relatively unchanged.
5. It is unclear how the studies were chosen for Table 2. Shouldnâ##t this table
be included in a sub-aim?
6. Could changes in the coding classification influence the estimates?
7. What do the authors understand by â##controlled studyâ##? Cohort study?
8. The authors acknowledge Astra-Zeneca under Acknowledgements. Such
funding, however, belongs under Competing Interest.