Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study

Background

Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal (GI) bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding.

Methods

We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months) and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day).

Results

581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57–1.96) or for whichever other grouping of antidepressants.

Conclusions

The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2.     

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications.     

A prospective study of aspirin use and the risk of gastrointestinal bleeding in men

Background and Aims

Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting.

Methods

We conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS) in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion.

Results

During 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week) had a multivariate relative risk (RR) of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12–1.55) compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16–1.92). Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71–1.52) for men who used 0.5–1.5 standard tablets/week, 1.31 (95% CI 0.88–1.95) for 2–5 aspirin/week, 1.63 (95% CI, 1.15–2.32) for 6–14 aspirin/week and 2.40 (95% CI, 1.10–5.22) for >14 aspirin/week (P_trend<0.001). The relative risk also appeared to be dose-dependent among short-term users <5 years; P_trend<.001) and long-term users (≥5 years; P_trend = 0.015). In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (P_trend = 0.749).

Conclusions

Regular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users.     

Migraine and risk of ischaemic stroke: a case-control study.

OBJECTIVES--To determine whether migraine is a risk factor for ischaemic stroke. DESIGN--A case-control study. SETTING--Two hospitals in Paris. SUBJECTS--212 patients with stroke (137 men and 75 women) and 212 controls matched for sex, age (to within five years), and history of hypertension. MAIN OUTCOME MEASURES--Ischaemic stroke, confirmed by brain computed tomography or magnetic resonance imaging, and history of headache, recorded with structured questionnaire during interview. RESULTS--Prevalence of migraine did not differ between patients with stroke and controls: 18/137 v 17/137 for men (odds ratio 1.1 (95% confidence interval 0.5 to 2.2), p = 0.86); 23/75 v 17/75 for women (odds ratio 1.6 (0.7 to 3.5), p = 0.24); and 41/212 v 34/212 for both sexes (odds ratio 1.3 (0.8 to 2.3), p = 0.33). When subjects were split into two age groups, however, prevalence of migraine was significantly higher among younger women (aged < 45) with stroke compared with their controls (13/20 v 6/20, odds ratio 4.3 (1.2 to 16.3), p = 0.03). Furthermore, the risk of ischaemic stroke was higher among younger women who smoked (7/20 v 1/20, odds ratio 10.2 (1.1 to 93.3)). CONCLUSIONS--Prevalence of migraine was not different between patients with stroke and matched controls except among women aged < 45, when migraine and stroke were significantly associated.     

Synergism between prior Anisakis simplex infections and intake of NSAIDs, on the risk of upper digestive bleeding: a case-control study

Background

The aim of this study was to investigate the relationship between prior Anisakis infections and upper gastrointestinal bleeding (UGIB), and its interaction with non-steroidal anti-inflammatory drug (NSAID) intake.

Methods/Principal Findings

We conducted a hospital-based case-control study covering 215 UGIB cases and 650 controls. Odds ratios (ORs) with their confidence intervals (95% CIs) were calculated, as well as the ratio of the combined effects to the sum of the separate effects of Anisakis allergic sensitization and NSAIDs intake. Prior Anisakis infections were revealed by the presence of anti-Anisakis IgE antibodies specific to the recombinant Ani s 1 and Ani s 7 allergens used as the targets in indirect ELISA. Prior Anisakis infections (OR 1.74 [95% CI: 1.10 to 2.75]) and the intake of NSAIDs (OR 6.63 [95% CI: 4.21 to 10.43]) increased the risk of bleeding. Simultaneous NSAIDs intake and Anisakis allergic sensitization increased the risk of UGIB 14-fold (OR = 14.46 [95% CI: 6.08 to 34.40]). This interaction was additive, with a synergistic index of 3.01 (95% CI: 1.18–7.71).

Conclusions

Prior Anisakis infection is an independent risk factor for UGIB, and the joint effect with NSAIDs is 3 times higher than the sum of their individual effects.     

A common SMAD7 variant is associated with risk of colorectal cancer: evidence from a case-control study and a meta-analysis

Background

A common genetic variant, rs4939827, located in SMAD7, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.

Method and Findings

We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all P for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.

Conclusion

Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.     

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study

Objectives

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants.

Background

Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood.

Methods

Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection.

Results

34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding.

Conclusions

Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.     

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

BackgroundWhile the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate.MethodsWe investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used.ResultsAdolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight.ConclusionIn postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.     

The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study

Numerous reports in the past few years have demonstrated that atherosclerosis is a lipid-driven, chronic inflammatory disease of the vessel. Recent studies have indicated that the immune mediator CD40-CD40L (CD40 ligand), which is expressed on several inflammatory cells within human atherosclerotic lesions, has roles in atherogenesis. A functional polymorphism (-1C>T, rs1883832) in the 5' untranslated region of TNFRSF5 gene has been reported to affect CD40 expression and be associated with several chronic inflammatory and autoimmune diseases. The aim of the present study was to validate the potential coronary artery disease susceptibility marker in a Chinese case-control study. A total of 160 patients with acute coronary syndrome (ACS) and 180 control subjects were used to genotype and identify this single-nucleotide polymorphism by polymerase chain reaction-restriction fragment length polymorphism and sequencing, respectively. Peripheral blood mononuclear cells were isolated and incubated with interferon-γ with or without pretreatment of fluvastatin, followed by measurement of CD40 expression using flow cytometry. In addition, soluble CD40L was determined by ELISA as another biomarker of coronary artery disease. The distribution of the rs1883832 genotypes (CC, CT, and TT) was 33.1%, 54.4%, and 12.5% in the ACS group and 22.8%, 53.3%, and 23.9% in controls, respectively. The frequency of the C allele was significantly higher among ACS patients compared with controls (60.3% vs. 49.4%, odds ratio=1.554, 95% confidence intervals: 1.146-2.107, p<0.05). ACS patients showed a significant increase of CD40 and sCD40L coexpression compared with controls (p<0.05). Cell culture experiments showed that CC carriers presented significantly higher CD40 expression levels than CT and TT subjects (p<0.05). Additionally, fluvastatin suppressed CD40 expression in all three genotypes. These data suggest that the single-nucleotide polymorphism of CD40 gene is associated with susceptibility to ACS in Chinese population, and the polymorphism may influence the CD40 production. These expand the understanding of inflammatory mechanisms during atherogenesis.     

Pet birds and risk of lung cancer in Sweden: a case-control study.

OBJECTIVE: To investigate the association between keeping birds and the risk of lung cancer in Sweden. DESIGN: Case control study based on cases of lung cancer and community controls. Interviews were performed by two nurses specially trained for this project. SETTING: Three major referral hospitals located in southwest Sweden. SUBJECTS: All patients aged 75 and under with newly diagnosed lung cancer and of Scandinavian birth who lived in one of 26 municipalities in Gothenburg and Bohus county or Alvsborg county. Potential control subjects matched on county of residence, sex, and closest date of birth were selected from population registries. In the context of a larger case-control study, information on pet birds was obtained from 380 patients with lung cancer (252 men) and 696 controls (433 men). MAIN OUTCOME MEASURES: Odds ratios for lung cancer in relation to whether or not pet birds were kept and the duration of keeping pet birds. RESULTS: The adjusted odds ratio for ever versus never exposed to pet birds at home was 0.94 (95% confidence interval 0.64 to 1.39) for men and 1.10 (0.64 to 1.90) for women. There was no evidence of a trend for increased risk of lung cancer with duration of bird ownership. CONCLUSION: Bird keeping does not seem to confer any excess risk of lung cancer to Swedish men or women.     

Soy consumption and risk of COPD and respiratory symptoms: a case-control study in Japan

Background

To investigate the relationship between soy consumption, COPD risk and the prevalence of respiratory symptoms, a case-control study was conducted in Japan.

Methods

A total of 278 eligible patients (244 men and 34 women), aged 50–75 years with COPD diagnosed within the past four years, were referred by respiratory physicians, while 340 controls (272 men and 68 women) were recruited from the community. All participants underwent spirometric measurements of respiratory function. Information on demographics, lifestyle characteristics and habitual food consumption was obtained using a structured questionnaire.

Results

Total soy consumption was positively correlated with observed lung function measures. The mean soy intake was significantly higher among controls (59.98, SD 50.23 g/day) than cases (44.84, SD 28.5 g/day). A significant reduction in COPD risk was evident for highest versus lowest quartile of daily intake of total soybean products, with adjusted odds ratio (OR) 0.392, 95% CI 0.194–0.793, p for trend 0.001. Similar decreases in COPD risk were associated with frequent and higher intake of soy foods such as tofu and bean sprouts, whereas respiratory symptoms were inversely associated with high consumption of soy foods, especially for breathlessness (OR 0.989, 95% CI 0.982–0.996).

Conclusion

Increasing soy consumption was associated with a decreased risk of COPD and breathlessness.     

The SNP rs961253 in 20p12.3 is associated with colorectal cancer risk: a case-control study and a meta-analysis of the published literature

Background

Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. A single nucleotide polymorphism (SNP), rs961253 located in 20p12, was firstly described to be associated with the increased risk of CRC in a genome-wide association study; however, more recent replication studies yielded controversial results.

Methodology/Principal Findings

A hospital-based case-control study in a Chinese population was firstly performed, and then a meta-analysis combining the current and previously published studies were conducted to explore the real effect of rs961253 in CRC susceptibility. In the Chinese population including 641 cases and 1037 controls, per-A-allele conferred an OR of 1.60 (95% CI = 1.26–2.02) under additive model. In the meta-analysis including 29859 cases and 29696 controls, per-A-allele have an OR of 1.13 (95% CI = 1.09–1.18) under a random-effects model due to heterogeneity (P = 0.019). Nevertheless, the heterogeneity can be totally explained by ethnicity, with the tau²reduced to 0 after including ethnicity in meta-regression model. In stratified analysis by ethnicity, per-A-allele had ORs of 1.34 (95% CI = 1.20–1.50) and 1.11 (95% CI = 1.08–1.14) for Asian and European, respectively, without heterogeneity. Modest influence of each study was observed on overall estimate in sensitive analysis, and evident tendency to significant association was seen in cumulative analysis over time, together indicating the robust stability of the current results.

Conclusions/Significance

The results from our study and the meta-analysis provided firm evidence that rs961253 significantly contributed to CRC risk in both Asian and European population.     

Salivary levels of mutans streptococci associated with restorations: a case-control study

Our aim was to estimate whether restorative therapy with amalgam and composite resin could decrease salivary mutans streptococcal level, thus also decreasing the risk for other caries development. We selected a case group of 93 children with detectable salivary mutans levels (i.e., at least 1x10(4) cfu/ml), and a control group (n=93 subjects) with undetectable levels. Children had the same age (12 years), no extracted teeth, crowns, temporary fillings, and restorations other than amalgam and composite resin, and the two groups had similar gender distribution. We clinically examined children and recorded active caries, restorations and oral hygiene level by means of gingival bleeding on probing; we also investigated sucrose intake at breakfast. The case group had statistically significant higher prevalence of restorations (36.6% vs. 18.3%), active caries (44.1% vs. 12.9%), and bad oral hygiene (84.9% vs. 68.8%) than the control group. However, the logistic regression analysis showed that presence of active caries was the only significant variable associated with mutans streptococci (OR=4.0; p=0.0002), while the effects of sucrose intake and of restorations were marginally significant. This apparent contrast between statistical analyses was due to the concomitant presence, in children with detectable mutans streptococci level, of restorations and decayed teeth at the same time, and, on the basis of the multivariate analysis, presence of mutans streptococci in these children was explained by the presence of active caries, more than restorations.