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Clinical and economic impact of “triple therapy” for Helicobacter pylori eradication on peptic ulcer disease in Australia
Abstract
Background
Helicobacter pylori infection has had a major impact on the global health of billions of people. Triple therapy was extensively used in Australia by 1986 for H pylori eradication after its discovery in 1984 and was critical in reducing the morbidity and mortality associated with this infection.
Aims
This study analyzed hospital admission, mortality, and therapeutic data to determine the economic and clinical impact that antibiotic triple therapy had on peptic ulcer disease (PUD) in Australia.
Methods
An analysis of indirect and direct cost‐savings in Australia between 1990 and 2015 associated with triple therapy and the impact on PUD mortality and hospital admissions.
Results
The direct and indirect impacts of PUD treated by triple therapy between 1990 and 2015 suggest that triple therapy is likely to have prevented 18 665 deaths, and saved 258 887 life years and 33 776 productive life years. The total savings, over the 26‐year period, including direct and indirect costs, are calculated to be $10.03 billion, equating to an average annual saving of $393.419 million.
Conclusions
This study highlights the enormous benefits to Australia's health care of the discovery of triple therapy, a relatively low‐cost antibiotic regimen which brought considerable savings via the reduction in morbidity (hospital admissions) and mortality related to PUD. It is likely that benefits of similar scale occurred internationally.
... A prime example was a treatment consisting of two antibiotics and bismuth for H. pylori (peptic ulcers), a previously intractable condition, which was shown to be 96% curative in a clinical trial conducted by Thomas Borody in 1990 [114]. That triple-therapy cure was rapidly deployed in Australia, preventing an estimated 18,665 deaths up through 2015 [115]. It was not widely used in the rest of the world, however, until the late 1990s, after the patents for two best-selling palliative drugs for that condition expired [116]. ...
Abstract: Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These
interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19.
Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three—SARS, SARS-CoV-2 and MERS—are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of
SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.
... A prime example was a treatment consisting of two antibiotics and bismuth for H. pylori (peptic ulcers), a previously intractable condition, which was shown to be 96% curative in a clinical trial conducted by Thomas Borody in 1990 [114]. That triple-therapy cure was rapidly deployed in Australia, preventing an estimated 18,665 deaths up through 2015 [115]. It was not widely used in the rest of the world, however, until the late 1990s, after the patents for two best-selling palliative drugs for that condition expired [116]. ...
Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three—SARS, SARS-CoV-2 and MERS—are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.
... Therapy has prevented 18,665 deaths, and saved 258,887 "life years." Direct and indirect cost savings were estimated, over this period, at in excess of ten billion dollars (Eslick et al., 2020). ...
... Following initial indications of efficacy for this combination therapy [43,44], an uncontrolled clinical trial conducted in Australia in 1990 by Thomas Borody reported 96% curative results for peptic ulcers using tetracycline, metronidazole and colloidal bismuth administered over four weeks [45]. Although clear RCT evidence of efficacy for that triple therapy was not amassed until 1992 [42], in Australia such combination treatments of peptic ulcers began to be used widely in the late 1980s, with a sharp drop in associated mortality beginning in 1990 and an estimated 18,665 deaths prevented between 1990 and 2015 [46]. However, this triple-therapy cure was not widely used in the rest of the world until the late 1990s, after the patents for Tagamet and Zantac expired [47]. ...
Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study’s data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise.
... However, there was a rise in the use of NSAIDs, mainly aspirin and other medicines, and these drugs frequently contribute to major consequences in individuals with PUD. In prior investigations, notably in Australia, a nation with an unexplained history of H. pylori, H. pylori infection was related with 70% to 90% of PUD patients [28,29]. Although these values are reduced in some other investigations, H. pylori infection is still a major component in the development of PUD [30]. ...
Background:Peptic ulcer disease (PUD) is a common disease of the gastrointestinal tract characterized by mucosal damage due to the secretion of pepsin and gastric acid. The current study aimed to determine the prevalence and causes of recurrent peptic ulcer. Methods:The current study adopted an exploratory study design in order to determine the prevalence and causes for recurrent peptic ulcer disease in individuals and predict an outcome. The participants for the current study were individuals belonging to the age group 18-75. This age group is chosen as the major influence of peptic ulcer disease is observed within this group.For the current study, questionnaire was adopted for data collection, which was also categorized as a study tool. Results:Study included 589 participants. It is noticed that most of participants (n= 530, 90.1%) strongly agree that they visit the doctor periodically to check on their health. Previous item has the highest rank followed by participants follow smoking lifestyle (n= 526, 89.4%). On the other hand, the least rank item on which participants strongly disagreed was participants suffered from soreness or bleeding from their stomach (n= 249, 42.4%). This gives a prevalence of 42.4% of peptic ulcer disease among study participants. Conclusion:Peptic ulcer illness burdens health care systems, which urge for adequate treatment to limit recurrence and effects. H. pylori, smoking, and aspirin usage are risk factors for 5-year peptic ulcer recurrence. Long-term PUD hazards include smoking and aspirin. Avoiding risk factors reduced the recurrence rate of H. pylori eradication, acid suppression medication, and surgery. This shows how eliminating risk factors may enhance long-term performance. Proper PUD treatment requires multicenter research to prevent recurrence and repercussions.
... Ikeda et al 28 demonstrated that H. pylori eradication triple therapy was less costly and more effective than histamine-2 receptor antagonist therapy for the treatment of peptic ulcers in Japan. Sonnenberg and Everhart showed that expenditures attributed to peptic ulcers, with significant damage to patients' health, amounted to US$5.65 billion peryear in the United States in 1989.29 Eslick et al30 found that triple therapy saved AU$10.03 billion including direct and indirect costs, prevented 18,665 deaths, and saved 258,887 life-years and 33,776 productive life-years in Australia between 1990 and 2015. They calculated indirect costs associated with excess mortality using a range of techniques and direct costs using the annual number of hospitalizations for peptic ulcer disease obtained from data in the National Hospital Morbidity Database in Australia and the cost of each hospitalization event based on data from the National Hospital Cost Data Collection. ...
Background:
Most peptic ulcer cases are associated with Helicobacter pylori (H. pylori) infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). H. pylori eradication therapy is recommended for the treatment of H. pylori-positive peptic ulcers. We aimed to assess and validate the cumulative economic and health effects of H. pylori eradication strategy for the treatment of peptic ulcers compared with PPI therapy strategy.
Materials and methods:
We developed a cohort state-transition model for H. pylori eradication strategy and PPI therapy strategy over a lifetime horizon from a healthcare payer perspective. We targeted two hypothetical cohorts of H. pylori-positive patients with gastric and duodenal ulcers aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, ulcer recurrence cases, and ulcer-associated deaths. One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty.
Results:
In the base-case analysis, H. pylori eradication strategy was less costly with greater benefits than PPI therapy strategy in all age groups. Cost-effectiveness was not sensitive to any variables in all age groups. Sensitivity analyses showed strong robustness of the results. From 2000 to 2020, H. pylori eradication strategy saved US$14.07 billion over a lifetime, increased 8.65 million QALYs and 1.23 million LYs over a lifetime, and prevented 551,298 ulcer recurrence cases and 59,465 ulcer-associated deaths, compared with PPI therapy strategy.
Conclusions:
H. pylori eradication strategy not only has contributed significantly to preventing ulcer recurrence and reducing ulcer-associated deaths but also has resulted in great cost savings. All over the world, H. pylori eradication strategy is likely to have yielded a comparable magnitude of economic and health benefits, depending on the epidemiology of H. pylori-related peptic ulcers and the healthcare environment in each country.
... However, there was an increase in the use of NSAIDs, especially aspirin and other drugs, and these drugs often lead to serious complications in patients with PUD. In previous studies, especially in Australia, a country with an inexplicable history of H. pylori, H. pylori infection was associated with 70% to 90% of PUD cases [18,19]. Although these values are lower in some other studies, H. pylori infection is still a key factor in the pathogenesis of PUD [20]. ...
Background
Peptic ulcer disease (PUD) is a common digestive disorder, of which the prevalence decreased in the past few decades. However, the decreasing tendency has plateaued in recent years due to changes in risk factors associated with the etiology of PUD, such as non-steroidal anti-inflammatory drug use. In this study, we investigated the epidemiological and the sociodemographic characteristics of PUD in 204 countries and territories from 1990 to 2019 based on data from the Global Burden of Disease, Injuries and Risk Factors (GBD) Study.
Methods
Demographic characteristics and annual prevalence, incidence, mortality, disability-adjusted life years (DALYs) and age-standardized death rate (ASR) data associated with PUD were obtained and analyzed. According to the sociodemographic index (SDI), the numbers of patients, ASRs, estimated annual percentage changes and geographical distributions were assessed with a generalized linear model and presented in world maps. All evaluations of numbers and rates were calculated per 100,000 population with 95% uncertainty intervals (UIs).
Results
In 2019, the global prevalence of PUD was approximately 8.09 [95% UI 6.79–9.58] million, representing a 25.82% increase from 1990. The age-standardized prevalence rate was 99.40 (83.86–117.55) per 100,000 population in 2019, representing a decrease of 143.37 (120.54–170.25) per 100,000 population from 1990. The age-standardized DALY rate in 2019 was decreased by 60.64% [74.40 (68.96–81.95) per 100,000 population] compared to that in 1990. In both sexes, the numbers and ASRs of the prevalence, incidence, deaths and DALYs were higher in males than in females over 29 years. Regionally, South Asia had the highest age-standardized prevalence rate [156.62 (130.58–187.05) per 100,000 population] in 2019. A low age-standardized death rate was found in the high-income super-region. Among nations, Kiribati had the highest age-standardized prevalence rate [330.32 (286.98–379.81) per 100,000 population]. Regarding socioeconomic status, positive associations between the age-standardized prevalence, incidence, death rate, DALYs and SDI were observed globally in 2019.
Conclusions
Morbidity and mortality due to PUD decreased significantly from 1990 to 2019, while a gradual upward inclination has been observed in recent 15 years, which might be associated with changes in risk factors for PUD. Attention and efforts by healthcare administrators and society are needed for PUD prevention and control.
... A 2010 review of the literature indicated that, in the West, dyspepsia is associated with "non-ulcer" or "functional" dyspepsia (73%), erosive esophagitis (13.4%), peptic ulcer (8%) and gastric cancer (0.4%) (2). Gastric cancer and peptic ulcer are associated with Helicobacter pylori (H pylori) infection, and its eradication has been claimed to reduce the relative risk of gastric cancer (RR = 0.67) (3), and to have prevented 18,665 peptic ulcer deaths in Australia between 1990 and 2015 (4). Yet, although about half of the world's population is infected, only a small proportion of people develop cancer and peptic ulcer; although both related to H. pylori infection, gastric cancer, and duodenal ulcer seem to be mutually exclusive (5); and during the last decades, there has been an unexplained worldwide decline in their prevalence (6)(7)(8) with the decline in peptic ulcer and gastric cancer preceding that of H pylori (9). ...
Background: The management of patients with dyspepsia is uncertain. Some authors advocate endoscopy for all; others restrict endoscopy only to patients at high risk of gastric cancer, namely to those above an age threshold, or with a family history, dysphagia, loss of weight, anemia, or a childhood in Asian countries. Still others recommend various combinations between test-and-treat for Helicobacter pylori, anti-secretory treatment, and/or endoscopy.
Objective: To highlight the uncertainties in the choice between the various strategies and argue that these uncertainties should be shared with the patient.
Method: An overview of reported life expectancy, patient satisfaction, gastric cancer detection rates, symptom relief, and cost effectiveness of the management strategies for dyspepsia.
Main Findings: There are no randomized controlled trials of the effect of screening by endoscopy on mortality of patients with gastric cancer. Lower grades of evidence suggest that early diagnosis reduces this mortality. Analyses, which assume a survival benefit of early diagnosis, indicate that mass screening in countries of high incidence gastric cancer (> 10 cases per 100,000) and targeted screening of high-risk persons in countries of low-intermediate incidence (<10 cases per 100,000) is cost-effective at a willingness to pay of $20,000–50,000 per QALY. Prompt endoscopy appears to be best for patient satisfaction and gastric cancer detection, and test-and-treat for H pylori—for symptom relief and avoiding endoscopies.
Conclusions: The gain in life expectancy is the main source of uncertainty in the choice between management strategies. This choice should be shared with the patients after explaining uncertainties and eliciting their preferences.
... In 1990, Dr Thomas J. Borody published the original clinical trial of a combination treatment for H. pylori, achieving a 96% cure rate for a triple therapy consisting of three repurposed drugs, bismuth subcitrate and two antibiotics [46]. Between 1990 and 2015, an estimated 18,665 deaths were prevented by the timely application of this triple therapy for peptic ulcer disease in Australia [47]. After the expiration of the patents for two palliative drugs for this condition, Tagamet and Zantac [48], which had each earned billions of dollars, triple therapy became the standard of care for peptic ulcers in the rest of the world by the late 1990s. ...
In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honored the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world’s most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. The RCT using the highest IVM dose achieved a 92% reduction in mortality vs. controls (400 total subjects, p<0.001). During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with extent of IVM distributions in all 25 states with p<0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus’s pathology. SARS-CoV-2 SP attaches to and aggregates red blood cells (RBCs), as shown in many pre-clinical and clinical studies, causing pulmonary and extrapulmonary microthrombi and hypoxia in severe COVID-19 patients. SARS-CoV-2 SP attachments to the heavily sialylated surfaces of platelets (which, like RBCs, have no ACE2) and endothelial cells (having minimal ACE2) compound this vascular damage. Notably, experimentally induced RBC aggregation in vivo causes the same key morbidities as for severe COVID-19, including microvascular occlusion, blood clots, hypoxia and myocarditis. Key risk factors for COVID-19 morbidity, including older age, diabetes and obesity, are all characterized by markedly increased propensity to RBC clumping. For mammalian species, the degree of clinical susceptibility to COVID-19 correlates to RBC aggregability with p = 0.033. Notably, of the five human betacoronaviruses, the two common cold strains express an enzyme that releases glycan attachments, while the deadly SARS, SARS-CoV-2 and MERS do not, although viral loads for COVID-19 and the two common cold infections are similar. These biochemical insights also explain the previously puzzling clinical efficacy of certain generics against COVID-19 and may support the development of future therapeutic strategies for COVID-19 and long COVID patients.
Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.
Background
Vonoprazan fumarate is a novel potassium-competitive acid blocker more effective in suppressing acid production than proton pump inhibitors (PPIs) and when combined with antibiotics has been used to eradicate Helicobacter pylori (H. pylori) infection. However, it has not yet been examined in an Australian setting. This study aimed to report on the efficacy and safety of vonoprazan-containing antibiotic combination therapies in the eradication of H. pylori.
Methods
A single-center, exploratory, clinical review of patients 18 years or over, positive for H. pylori on Urea Breath Test (UBT), and/or histopathology who underwent a 10-day treatment of combination antibiotics plus vonoprazan between January 2017 and September 2019 was conducted. Eleven different combinations of antibiotics that included 2–5 different antibiotics predominantly amoxicillin, rifabutin, levofloxacin, furazolidone, nitazoxanide, and tetracycline were included. The eradication success was based on negative UBT results and/or histopathology results after the treatment. Descriptive statistics were summarized.
Results
One hundred and fifty-three patients (Female n = 74, 48%) with a positive for H. pylori were treated with vonoprazan-containing antibiotic combination therapy during the study period. Of the 153 patients, 48 (31%) had previously failed a PPI-based H. pylori treatment. Follow-up was available for 66/153 (43%) patients. In those who completed follow-up, overall eradication was achieved in 97% (64/66) of patients. In the subgroup of patients treated for the first time, eradication was achieved in 100% (44/44). In those who had failed prior, non-vonoprazan-containing treatment, eradication was achieved in 91% (20/22) of patients.
Conclusions
Vonoprazan-containing antibiotic therapy is an effective H. pylori eradication treatment. It is capable of achieving 100% efficacy in patients treated for the first time and even 91% efficacy in patients with previous eradication failure. Subsequent studies utilizing a factorial design will be needed to optimize each regimen as most regimens contained more than two antibiotics.
Background:
The epidemiology of Helicobacter pylori infection is poorly understood.
Aim:
To establish the reported regional and national prevalence of H. pylori infection, stratified by age and gender.
Methods:
All relevant English publications from 2000 to 2017 cited by PubMed and Scopus were retrieved using comprehensive combinations of keywords. The overall prevalence of H. pylori was estimated using both random effect and fixed effect meta-analyses, and presented as prevalence rate (% and 95% CI). The analyses were extended by separation into gender and age groups.
Results:
A total of 14 056 records were obtained initially. After applying exclusion criteria in several steps, 183 studies were selected. Analysis of 410 879 participants from 73 countries in six continents revealed an overall prevalence of 44.3% (95% CI: 40.9-47.7) worldwide. This rate ranged from 50.8% (95% CI: 46.8-54.7) in developing countries compared with 34.7% (95% CI: 30.2-39.3) in developed countries. The global H. pylori infection rate was 42.7% (95% CI: 39-46.5) in females compared to 46.3% (95% CI: 42.1-50.5) in males. The prevalence in adults (≥18 years) was significantly higher than in children (48.6% [95% CI: 43.8-53.5] vs 32.6% [95% CI: 28.4-36.8], respectively). There was a statistically nonsignificant decrease in the prevalence in 2009-2016 compared with the 2000-2009 period.
Conclusions:
The observed differences between countries appear to be due to economic and social conditions. H. pylori infection can be a benchmark for the socioeconomic and health status of a country. Further studies are suggested to investigate the natural history of the acquisition of H. pylori infection from childhood into adult life.
Background & aims:
The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection.
Methods:
We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% CIs, weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection.
Results:
Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI 62.6-77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI 18.5-30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI 13.1-24.7) to 87.7% in Nigeria (95% CI 83.1-92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015.
Conclusions:
In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions-more than half the world's population is infected. These data can be used in development of customized strategies for the global eradication.
Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longeracting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.
Helicobacter pylori infection is a major cause of morbidity and mortality worldwide. More than 50% of the global population is estimated to be infected. Differences in prevalence exist within and between countries, with higher prevalence seen among people with lower socio-economic status. Most transmission of infection occurs early in life, predominantly from person to person in the family setting. H. pylori is the cause of most peptic ulcer disease, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and causes symptoms in a subset of patients with functional dyspepsia. Choice of diagnostic test depends on the clinical context; urea breath tests and endoscopy with biopsy are the major diagnostic tools. Evidence-based indications for eradication of H. pylori infection are well documented. The most widely used and recommended eradication therapy in Australia is triple therapy comprising a proton pump inhibitor, amoxycillin and clarithromycin, usually for 1 week. Effective alternative regimens are available for patients with proven allergy to penicillin. Antimicrobial resistance is the major determinant of the outcome of eradication therapy. Trends in antibiotic resistance need to be monitored locally, but individual patient susceptibility testing is not usually necessary as it rarely guides the choice of therapy. The outcome of treatment should be assessed not less than 4 weeks after therapy. This is usually done with a urea breath test if follow-up endoscopy is not required. When first-line therapy fails, several proven second-line therapies may be used. Repeat first-line therapy and ad hoc regimens should be avoided. Overall cumulative eradication rates should approach 99%.
Background:
Gastroenterology has over the past 30 years evolved very rapidly. The societal benefits to which this has led are incompletely determined, yet form a mandate to determine the need for future innovations and further development of the field. A more thorough understanding of societal benefits may help to determine future goals and improve decision making.
Aims:
The objective of this article is to determine the societal gains of medical innovations in the field of gastroenterology in the past and future, using peptic ulcer disease as an example of past innovation and the implementation of colorectal cancer screening as an illustration of future gains.
Methods:
Literature searches were performed for data on peptic ulcer and colorectal cancer epidemiology, treatment outcomes, and costs. National and governmental databases in the Netherlands were searched to obtain the input for calculations of quality-adjusted life years (QALYs), health-adjusted life expectancy (HALE), and the corresponding societal benefit.
Results:
Since 1980 the improvements in peptic ulcer treatment have had a limited impact on life expectancy, rising from 83.6 years to 83.7 years, but have led to a yearly gain of 46,000 QALYs, caused by improved quality of life. These developments in the field of peptic ulcer translated into a yearly gain of 1.8 billion to 7.8 billion euros in 2008 compared with the 1980s. Mortality due to colorectal cancer is high, with 21.6 deaths per 100,000 per year in the Netherlands (European Standardized Rate (ESR)). The future implementation of a nationwide call-recall colorectal cancer screening by means of biennial fecal immunochemical testing (FIT) is expected to result in a 50%-80% mortality reduction and thus a gain of an estimated 35,000 life years per year, corresponding to 26,000 QALYs per year. The effects of the implementation of FIT screening can be translated to a future societal gain of 1.0 billion to 4.4 billion euro.
Conclusions:
The innovations and developments in the field of gastroenterology have led to significant societal gains in the past three decades. This process will continue in the near future as a result of further developments. These calculations provide a template for calculations on the need for specialist training as well as research and implementation of new developments in our field.
The Gram negative curved bacillus H. pylori has become the prize bug of all times. Barry Marshall and Robin Warren the two discoverers of this organism have been awarded with this year's Nobel Prize. The Nobel committee at the Karolinska Institute of Sweden has selected this paradigm shift discovery of 1982 as the most impacting in medical sciences. This award has surprised many as the Nobel assembly has selected this 'Robert Koch styled medical detective work' for the prize as compared to many outstanding basic research stories on the waitlist. This editorial briefly touches the significant impact of H. pylori on gastroduodenal management and the path forward as the bug has become quite controversial in recent times.
Background: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. Objectives: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people. To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores. To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments. To assess the proportion of participants in whom successful eradication was achieved. Search methods: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. Selection criteria: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. Data collection and analysis: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. Main results: A total of 55 trials were included for one or more outcomes for this review. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence). In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. Authors' conclusions: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori (H. pylori) infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple, quadruple, or sequential therapy regimens. The central aim of this systematic review is to evaluate the evidence for H. pylori therapy from a meta-analytical outlook. The consequence of the dose, type of proton-pump inhibitor, and the length of the treatment will be debated. The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.
Although Helicobacter pylori infection is both a common and a serious bacterial infection, antimicrobial therapies have rarely been optimized, are prescribed empirically, and provide inferior results compared with antimicrobial therapies for other common infectious diseases. The effectiveness of many of the frequently recommended H. pylori infection treatment regimens has been increasingly compromised by antimicrobial resistance. Regional data on the susceptibility of strains of H. pylori to available antimicrobials are sorely needed. Noninvasive molecular methods are possible to assess clarithromycin susceptibility in isolates obtained from stool specimens. As a general rule, clinicians should prescribe therapeutic regimens that have a ≥90% or, preferably, ≥95% eradication rate locally. If no available regimen can achieve a ≥90% eradication rate, clinicians should use the most effective regimen(s) available locally. Eradication of infection should always be confirmed after treatment in order to provide feedback regarding local effectiveness and an early warning of increasing resistance. In most regions of the world, four-drug treatment regimens, including a PPI plus three antimicrobials (clarithromycin, metronidazole/tinidazole and amoxicillin), or a PPI plus a bismuth plus tetracycline and metronidazole provide the best results. Standard triple therapy (a PPI, amoxicillin and clarithromycin) should now be avoided owing to increasing resistance to this treatment.
The objective of this study is to review current measurement issues and valuation methods such as "human capital" and "friction cost" for estimating productivity loss due to illness. Since observed wages diverge from marginal productivity when allowances are made for sick days and workers are risk averse, or when a job type involves team production, unavailability of perfect substitutes, and/or time-sensitivity of output, productivity loss is likely to be underestimated. A multiplier adjusting wage to marginal productivity needs to be developed for practical use. We further consider the ramifications of measuring labour input loss due to illness in both paid and unpaid work as well as the inclusion of presenteeism to the more traditional approach of measuring only absenteeism. Although a number of instruments have been developed to measure presenteeism, they generate widely varying estimates of productivity loss. Further investigation is required to identify which instrument provides a better estimate. Finally, we provide recommendations on measurement methods such as using subjective measures due to the unavailability of objective measures and the appropriate recall periods. We conclude by proposing a generic measure instead of a disease-specific measure and discuss important perspective related issues.
To examine the trends in the prescribing of subsidized proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidized Pharmaceutical Benefits Scheme (PBS).
Government data on numbers of subsidized scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication.
Drug utilisation as DDD [defined daily dose]/1000 population/day.
The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidized indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years.
PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines.
Chronic infection of the stomach with Helicobacter pylori is widespread throughout the world and is the major cause of peptic ulcer disease and gastric cancer. Short-term benefit results from community programmes to eradicate the infection, but there is little information on cumulative long-term benefit.
To determine whether a community programme of screening for and eradication of H. pylori infection produces further benefit after an initial 2-year period, as judged by a reduction in GP consultations for dyspepsia.
A total of 1517 people aged 20-59 years, who were registered with seven general practices in Frenchay Health District, Bristol, had a positive (13)C-urea breath test for H. pylori infection and were entered into a randomized double-blind trial of H. pylori eradication therapy. After 2 years, we found a 35% reduction in GP consultations for dyspepsia (previously reported). In this extension to the study, we analysed dyspepsia consultations between two and 7 years after treatment.
Between two and 7 years after treatment, 81/764 (10.6%) of participants randomized to receive active treatment consulted for dyspepsia, compared with 106/753 (14.1%) of those who received placebo, a 25% reduction, odds ratio 0.84 (0.71, 1.00), P = 0.042.
Eradication of H. pylori infection in the community gives cumulative long-term benefit, with a continued reduction in the development of dyspepsia severe enough to require a consultation with a general practitioner up to at least 7 years. The cost savings resulting from this aspect of a community H. pylori eradication programme, in addition to the other theoretical benefits, make such programmes worthy of serious consideration, particularly in populations with a high prevalence of H. pylori infection.
Eighty-two patients, whose duodenal ulcers were recurrent or resistant to H2-receptor antagonist therapy, were entered in a treatment protocol of ranitidine followed by a four-week "triple therapy" course to eradicate Helicobacter pylori (HP) infection. The triple therapy consisted of colloidal bismuth subcitrate, tetracycline and metronidazole. Duodenal ulcer healed in all 78 patients available for endoscopy and H. pylori infection was shown to be eliminated in 75 patients (96%) at rebiopsy four weeks after cessation of therapy. In these 75 remaining patients the relapse rates for H. pylori infection and duodenal ulcer were studied endoscopically, yearly and at any recurrence of symptoms. At Year 1, 71 of 73 patients remained free of H. pylori infection (HP-negative) and duodenal ulcer. The corresponding figures subsequently were: Year 2, 57/57; Year 3, 34/34; Year 4, 15/15. No duodenal ulcers recurred in HP-negative patients who were followed for up to four years. Two patients of the original cohort of 75 HP-negative patients were HP-positive with endoscopic duodenitis at 12 months, and one at 36 months, but all were without reulceration. Distorted duodenal caps gradually returned to near-normal appearance in 80% of patients by two years. From this four-year follow-up study we conclude that duodenal ulcer disease will not recur provided the patient remains free of H. pylori.
The role of Campylobacter pylori gastritis in dyspepsia could be clarified more readily if reliable eradication therapy were available. Antibiotic monotherapy and combined therapy with an antibiotic agent plus a bismuth compound have yielded poor long-term results. In this study, bismuth-tetracycline-metronidazole triple therapy has been used to eradicate C. pylori infection in 100 consecutive patients who were suffering from either a duodenal ulcer or non-ulcer dyspepsia. Examination of a follow-up endoscopic biopsy at eight weeks after treatment showed an eradication rate of C. pylori of 94%. Of 64 patients whose biopsy samples were free of C. pylori infection at eight weeks and who were available for reassessment, 60 (94%) patients had samples that remained free of C. pylori infection on examination of a repeat endoscopic biopsy at 12-37 months (mean, 19.3 months). It is concluded that "triple chemotherapy" can achieve long-term eradication of C. pylori infection effectively in the majority of treated patients and that the recurrence of duodenal ulcers thus may be diminished.
Campylobacter pyloridis is a spiral bacterium which was seen by histopathologists several years before it was cultured in 1982 in Perth, Western Australia. It has unique cellular fatty acids, predominantly tetradecanoic acid and cis-11, 12 methylene octadecanoic acid. It also has a unique ultrastructure which is different from that of other campylobacters. C pyloridis possesses a powerful urease enzyme and produces large amounts of extracellular catalase. Both these features may be important virulence factors, allowing it to occupy a protected niche in the stomach below the mucus layer but above the gastric mucosa. Specific lesions are found in the gastric mucosa, and ultrastructural studies show the presence of adherence pedestals identical with those found with enteropathogenic Escherichia coli of the intestine. Histological examination of gastric biopsy tissue has shown that C pyloridis is strongly associated with active chronic gastritis, when polymorphonuclear leucocytes are present, and is not found on normal mucosa except when a biopsy specimen from elsewhere in the stomach shows active chronic gastritis. When patients with symptoms caused by gastritis are identified dual antibacterial treatment, combining the action of bismuth in the stomach with a systemic antibiotic, can eradicate C pyloridis, with remission of symptoms and restoration of normal epithelial morphology. Most peptic ulcers relapse after modern acid reducing treatment, and antibacterial treatment may be beneficial in preventing relapse.
A volunteer with histologically normal gastric mucosa received pyloric campylobacter by mouth. A mild illness developed, which lasted 14 days. Histologically proven gastritis was present on the tenth day after the ingestion of bacteria, but this had largely resolved by the fourteenth day. The syndrome of acute pyloric campylobacter gastritis is described. It is proposed that this disorder may progress to a chronic infection which predisposes to peptic ulceration.
Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.
A study of Pharmaceutical Benefits Scheme cimetidine prescriptions, hospital admissions, and deaths due to peptic ulcer in 13 million Australians in 1981 indicated that the annual ulcer incidence per 1000 population was 3.8 for duodenal ulcer and 0.7 for gastric ulcer. Approximately 70 000 Australians appear to receive initial treatment for a peptic ulcer each year. Two-thirds of patients were managed outside hospital. Patients with gastric ulcers were more likely to be admitted to hospital or to die from their ulcer than were patients with duodenal ulcers. Significant regional differences in ulcer frequency were found; in particular, the risk of gastric ulcer in NSW was four times that in Victoria. Gastric and duodenal ulcers were more common in New South Wales than in Victoria, Queensland or Western Australia. These differences, and other regional variations, indicate appropriate localities for further studies of the aetiology of peptic ulcer.
It remains unclear whether acquisition of Helicobacter pylori is due to a continuous risk of acquiring the infection or a cohort effect. In this prospective 3-year cohort study, the seroprevalence,
conversion, and reversion of H. pylori infection as determined by IgG antibodies was examined. The cohort consisted of 316 randomly selected, nonpatient subjects
aged 18-72 years who each provided at least 2 suitable samples. Seroprevalence of H. pylori increased from 21%in the third decade to 50% in the eighth decade. Crude annual seroconversion rate was 1% and the “spontaneous”
seroreversion rate was 1.6%. Age was the only identified risk factor for H. pylori infection. A continuous risk of acquisition of 1%/year rather than a cohort effect best explains the pattern of H. pylori infection in this Canadian population. Seroconversion continues in adult life, and spontaneous reversions do occur, especially
in the later decades.
A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalenee has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude
of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%–41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort
effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that
H. pylori infection is becoming less frequent and is predominantly acquired in childhood.
To assess the general outcome and impact of current and previous peptic ulcer disease on health status in the United States.
During the National Health Interview Survey of 1989, a special questionnaire on digestive diseases was administered to 41,457 randomly selected individuals. Various measures of impaired health in ulcer patients were expressed by their age- and sex-standardized prevalence rates.
Ten to 15% of all subjects with a recent ulcer reported that they had been in poor health, incapable of major activity, or unable to work for some time during the 12 months preceding the interview. Twenty to 25% of the subjects with recent ulcers complained about restricted activity and had spent 7 or more days per year in bed. About 40% of all ulcer subjects had seen a physician five or more times within 12 months before the interview. These percentages were significantly lower in patients with previous ulcer histories but no active ulcer within 12 months, but they were still significantly higher than in subjects with no ulcer history at all. In the United States, expenditures attributed to recent ulcers amounted to $5.65 billion per year.
In the United States, peptic ulcer disease is associated with major morbidity. Ulcer cure would result in large economic and medical savings.
Direct comparisons of bismuth and proton pump inhibitor (PPI)-based triple and quadruple therapies for Helicobacter pylori eradication are lacking. To address this, a randomized study was conducted.
Infected dyspeptic patients received pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily, for 7 days (PAC7); or pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 7 days (PBTM7); bismuth subcitrate 108 mg and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 14 days (BTM14). Outcome was assessed with (13)C-urea breath test.
Eradication rates (intention to treat [n = 405]/per protocol [n = 320]) were similar for PAC7 (78%/82%) and PBTM7 (82%/88%); the latter significantly superior to BTM14 (69%/74%; P < 0.01). Pretreatment metronidazole resistance (MR) was 53% and clarithromycin resistance was 8%. Eradication rates for primary metronidazole sensitive/resistant isolates were 74%/87% with PAC7 and 80%/81% for PBTM7, compared with 76%/55% (P < 0.02) for BTM14. Noncompliance was greater with BTM14 (15%; P < 0.001) than PAC7 (3%) or PBTM7 (6%). Moderate-severe adverse events were more common with BTM14 (45%; P < 0.001), than PAC7 (23%) or PBTM7 (25%) with more discontinuations (9%, 2%, 3%, respectively).
One-week PPI triple therapy is well tolerated and effective. The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of MR. Quadruple therapy appears to overcome pretreatment MR in most cases. Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both 1-week therapies.
According to data from the Institute for Scientific Information (ISI), the most-cited MJA article is Cade's ground-breaking report on the effect of lithium in mania (1949; 888 citations), followed by Marshall et al's reports on the role of Helicobacter pylori in gastroduodenal disease (1985; 766 and 523 citations, respectively). Others in the "top 10" span decades and disciplines; all have a common grounding in Australian data of global relevance.
The frequency of surgery for peptic ulcer disease (PUD) has decreased dramatically during the last 3 decades. The purpose of this study was to characterize the Veteran patients undergoing surgery for peptic ulcer disease in a modern series and to examine the effect of H. pylori status on surgical outcome and recurrence of PUD.
An Institutional Review Board-approved retrospective review of all patients undergoing operations for peptic ulcer disease during a 66-month period at a single Veterans Administration medical center was performed. Patient records were examined for demographics, medication use, Helicobacter pylori status, operative details, and surgical outcomes.
From January 1999 to July 2004, 43 of 128 upper gastrointestinal operations were performed for PUD. Thirty-five operations (81%) were performed for bleeding or perforated ulcers, and 26 (60%) patients had no history of PUD. The mean age was 60 years, and 66% of patients were American Society of Anesthesiologists (ASA) class 3 or 4; 47% were Helicobacter pylori positive, and 54% used nonsteroidal anti-inflammatory (NSAID) medication. Hospital mortality was 23%. By univariate analysis, emergent surgery, higher ASA status, H. pylori status, and absence of a history of ulcer disease were risk factors for mortality (P <.05). Only 36% underwent definitive ulcer surgery. With a median follow-up of 18 months, there has been only 1 single recurrence (3%).
PUD still accounts for 33% of all gastroduodenal surgery performed in a Veterans Administration medical center. The majority of these operations are emergent operations in high-risk patients. In this era of effective acid suppression and H. pylori treatment, definitive ulcer surgery in the emergent setting may not be necessary.
The Helicobacter story illustrates some of the human hallmarks of revolutionary research.
Triple therapy, consisting of two antibiotics, clarithomycin and amoxicillin or metronidazole in combination with a proton pump inhibitor (PPI) has become the first-line option for infection with Helicobacter pylori and has been recommended at several consensus conferences. In clinical practice, approximately 20% of patients will fail to obtain H. pylori eradication with the recommended treatment regimens. Major causes of treatment failure are insufficient patient compliance and antibiotic resistance. Because of antibiotic resistance, bismuth-based quadruple therapy has also become a first-line regimen in areas with exceedingly high rates of clarithromycin and metronidazole resistance, and is the preferred second-line option otherwise. Triple therapies based on levofloxacin and/or rifabutin mainly with combination of amoxicillin are options if multiple eradication failure occurs. However, following therapy failure beyond a second treatment attempt requires antibiotic resistance testing. New drugs and adjuvant agents have been reported but their efficacy needs further evaluation.
To analyze the relative influence of factors in decisions for public insurance coverage of new drugs in Australia.
Evidence presented at meetings of the Australian Pharmaceutical Benefits Advisory Committee (PBAC) that makes recommendations on coverage of drugs under Pharmaceutical Benefits Scheme.
All major submissions to the PBAC between February 1994 and December 2004 (n = 858) if one of the outcomes measured was life year gained (n=138) or quality-adjusted life years (QALYs) gained (n=116).
Clinical significance, cost-effectiveness, cost to government, and severity of disease were significant influences on decisions. Compared to the average submission, clinical significance increased the probability of recommending coverage by 0.21 (95% confidence interval [CI] 0.02 to 0.40), whereas a drug in a life-threatening condition had an increased probability of being recommended for coverage of 0.38 (0.06 to 0.69). An increase in $A10,000 from a mean incremental cost per QALY of $A46,400 reduced the probability of listing by 0.06 (95% CI 0.04 to 0.1).
The PBAC provides an example of the long-term stability and coherence of evidence-based coverage and pricing decisions for drugs that weighs up the evidence on clinical effectiveness, clinical need, and value for money. There is no evidence of a fixed public threshold value of life years or QALYs, but willingness to pay is clearly related to the characteristics of the clinical condition, perceived confidence in the evidence of effectiveness and its relevance, as well as total cost to government.
We have documented the changing pattern of peptic ulcer disease in our centre in the last quarter of the 20th century and speculate on the reasons thereof.
The profile of peptic ulcer disease patients presenting newly to our centre (population 250,000) from 1977 to 2001 was examined. All patients were prospectively followed and detailed records kept. Results are presented in 5-year periods.
Seven thousand five hundred and ninety new peptic ulcer disease patients (5564 duodenal ulcer+2026 gastric ulcer) were seen, peaking in 1982-1986 but declining thereafter, and with a falling male preponderance. Patients with gastric ulcer were older than those with duodenal ulcer; were older than duodenal ulcer, the mean age of both increased over time and the age gap from the general population widened. The numbers presenting with perforation changed little but haemorrhage increased, particularly amongst the elderly. Ulcers refractory to H2 receptor antagonists declined even before proton pump inhibitors were introduced. Elective surgery, already declining before H2 receptor antagonists, had virtually disappeared by 1992-1996.
Peptic ulcer disease affects an older population, an increasing proportion of whom present with haemorrhage. Refractoriness to H2 receptor antagonists and the need for elective operation was declining even before the emergence of modern treatment. We suggest the changes observed result not only from modern therapy but also substantially from a changing natural history.
Marshall BJ Campylobacter pylordis, gastritis, and peptic ulceration
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A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study
- PH Katelaris
- GM Forbes
- NJ Talley
- B Cotty
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Establishing a monetary value for lives saved: issues and controversies Working Papers in Cost benefit Analysis WP 2008-2 Department of Finance and Deregulation
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Axon ATRV Helicobacter pylori therapy: effect on peptic ulcer disease
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