Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among long-term PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison. Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12-2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90, 95% CI 4.26-16.37), and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54-3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38-1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66-1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users

Maintenance therapy with proton pump inhibitors and risk of gastric cancer : a nationwide population-based cohort study in Sweden

Objective: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications. Design: This is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account. Setting: Population-based study in Sweden (2005-2012). Participants: This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs. Exposure/Intervention: Maintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons. Outcome measures: Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry. Results: Among 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk. Conclusions: Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak

Общие принципы обязательного страхования от несчастных случаев на производстве и профессиональных заболеваний

Материалы IV Междунар. науч.-практ. конф., Гомель, 17–18 нояб. 2005 г

Helicobacter pylori genome variability in a framework of familial transmission

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>infection is exceptionally prevalent and is considered to be acquired primarily early in life through person-to-person transmission within the family. <it>H. pylori </it>is a genetically diverse bacterial species, which may facilitate adaptation to new hosts and persistence for decades. The present study aimed to explore the genetic diversity of clonal isolates from a mother and her three children in order to shed light on <it>H. pylori </it>transmission and host adaptation.</p> <p>Results</p> <p>Two different <it>H. pylori </it>strains and strain variants were identified in the family members by PCR-based molecular typing and sequencing of five loci. Genome diversity was further assessed for 15 isolates by comparative microarray hybridizations. The microarray consisted of 1,745 oligonucleotides representing the genes of two previously sequenced <it>H. pylori </it>strains. The microarray analysis detected a limited mean number (± standard error) of divergent genes between clonal isolates from the same and different individuals (1 ± 0.4, 0.1%, and 3 ± 0.3, 0.2%, respectively). There was considerable variability between the two different strains in the family members (147 ± 4, 8%) and for all isolates relative to the two sequenced reference strains (314 ± 16, 18%). The diversity between different strains was associated with gene functional classes related to DNA metabolism and the cell envelope.</p> <p>Conclusion</p> <p>The present data from clonal <it>H. pylori </it>isolates of family members do not support that transmission and host adaptation are associated with substantial sequence diversity in the bacterial genome. However, important phenotypic modifications may be determined by additional genetic mechanisms, such as phase-variation. Our findings can aid further exploration of <it>H. pylori </it>genetic diversity and adaptation.</p

Susceptibility to Campylobacter Infection Is Associated with the Species Composition of the Human Fecal Microbiota

Peer reviewe

Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population

OBJECTIVE: Gastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population. DESIGN: This was a nationwide, population-based cohort study in Sweden in 2005-2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs. RESULTS: During the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1-3 years, 2.02 (95% CI 1.25 to 3.09) for 3-5 years and 0.31 (95% CI 0.11 to 0.67) for 5-7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93). CONCLUSION: Eradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.Strategic Research Area (SFO)Karolinska Institutet internal funding for doctoral education (KID funding)Swedish Society of MedicineSwedish Research CouncilSwedish Cancer SocietyManuscrip

Antibiotic use and risk of colorectal cancer : a systematic review and dose-response meta-analysis

Background It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present. Design Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose-response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models. Results Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05-1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26-2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93-1.32). The dose-response analysis did not provide strong evidence of any particular dose-response association, and the risk patterns were rather similar for colon and rectal cancer. Discussion The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug-microbiome interactions

Eradication of Helicobacter pylori and gastric and oesophageal cancer : a systematic review and meta-analysis of cohort studies

Background: Helicobacter pylori (H. pylori) is associated with an increased risk of gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma, and a seemingly decreased risk of oesophageal adenocarcinoma. We aimed to assess how eradication therapy for H. pylori influences the risk of developing these cancers. Methods: This was a systematic review and meta-analysis. We searched PubMed, Web of Science, Embase and the Cochrane Library and selected articles that examined the risk of gastric cancer, MALT lymphoma or oesophageal cancer following eradication therapy, compared to a non-eradicated control group. Results: Among 3629 articles that were considered, 9 met the inclusion criteria. Of these, 8 cohort studies assessed gastric cancer, while 1 randomized trial assessed oesophageal cancer. Out of 12,899 successfully eradicated patients, 119 (0.9%) developed gastric cancer, compared to 208 (1.1%) out of 18,654 non-eradicated patients. The pooled relative risk of gastric cancer in all 8 studies was 0.46 (95% confidence interval 0.32-0.66, I2 32.3%) favouring eradication therapy. The 4 studies adjusting for time of follow-up and confounders showed a relative risk of 0.46 (95% confidence interval 0.29-0.72, I2 44.4%). Conclusion: This systematic review and meta-analysis indicates that eradication therapy for H. pylori prevents gastric cancer. There was insufficient literature for meta-analysis of MALT lymphoma or oesophageal cancer.Swedish Research Council (SIMSAM), Swedish Cancer Society, and Strategic Research Area (SFO)Manuscrip