Association between antibiotic consumption and colon and rectal cancer development in older individuals: A territory‐wide study

Background: Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in older individuals. Methods: This was a territory-wide retrospective cohort study. Subjects aged 60 years and older who did not have CRC diagnosed on screening/diagnostic colonoscopy diagnosed between 2005 and 2013 were recruited. Exclusion criteria were history of CRC, colectomy, inflammatory bowel disease, and CRC diagnosed within 6 months of index colonoscopy. Exposure was use of any antibiotics up to 5 years before colonoscopy. The primary outcomes were CRC diagnosed >6 m after colonoscopy. Covariates were patient demographics, history of colonic polyps/polypectomy, concomitant medication use (NSAIDs, COX-2 inhibitors, aspirin, and statins), and performance of endoscopy centers (colonoscopy volume and polypectomy rate). Stratified analysis was conducted according to nature of antibiotics and location of cancer. Results: Ninety seven thousand one hundred and sixty-two eligible subjects (with 1026 [1.0%] cases of CRC) were identified, 58,704 (60.4%) of whom were exposed to antibiotics before index colonoscopy. Use of antibiotics was associated with a lower risk of cancer in rectum (adjusted hazard ratio [aHR]: 0.64, 95% CI: 0.54–0.76), but a higher risk of cancer in proximal colon (aHR: 1.63, 95%CI: 1.15–2.32). These effects differed as regards the anti-anaerobic/anti-aerobic activity, narrow-/broad-spectrum, and administration route of antibiotics. Conclusions: Antibiotics had divergent effects on CRC development in older subjects, which varied according to the location of cancer, antibiotic class, and administration route

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication.

BACKGROUND: Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. METHODS: This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. RESULTS: During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. CONCLUSIONS: Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level

Statins Were Associated with a Reduced Gastric Cancer Risk in Patients with Eradicated Helicobacter Pylori Infection: A Territory-Wide Propensity Score Matched Study.

BACKGROUND: Individuals may still develop gastric cancer even after Helicobacter pylori eradication. We aimed to investigate statin effect on gastric cancer development in H. pylori-eradicated subjects. METHODS: All adult subjects who were prescribed clarithromycin-based triple therapy between 2003 and 2012 were identified in this retrospective cohort study utilizing a territory-wide electronic healthcare database. Patients were observed from index date of H. pylori therapy, and censored at gastric cancer diagnosis, death, or December 2015 (study end date). Statin use was defined as ≥180-day use after index date. Exclusion criteria included gastric cancer diagnosed within the first year after index date, previous gastric cancer or gastrectomy, and H. pylori treatment failure. Subdistribution hazard ratio (SHR) of gastric cancer with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities, and other drug usage, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin). RESULTS: During a median follow-up of 7.6 years (interquartile range = 5.1-10.3), 169 (0.27%) of 63,605 patients developed gastric cancer at an incidence rate of 3.5 per 10,000 person-years. Among 22,870 PS-matched subjects, statins were associated with a lower gastric cancer risk (SHR = 0.34; 95% confidence interval, 0.19-0.61), in a duration- and dose-response manner (P trend < 0.05). CONCLUSIONS: Statins were associated with a lower gastric cancer risk in a duration- and dose-response manner among H. pylori-eradicated patients. IMPACT: This study provides evidence on the additional benefits of statins as chemopreventive agents against gastric cancer among H. pylori-eradicated patients

Evidence of individual differences in the long-term social, psychological, and cognitive consequences of child maltreatment

Background: The prevalence and consequences of child maltreatment are alarming, but evidence from studies with long follow-up intervals are limited. This study examined the long-term consequences of child maltreatment in relation to age of onset and follow-up interval. / Methods: The exposed group comprised 63 individuals (aged 13–34 years) with a first-time diagnosis of child maltreatment between 2001 and 2010, whereas the unexposed group comprised 63 individuals who were matched upon gender, age of onset, follow-up period, and poverty status at the index hospital admission but had no medical records of maltreatment in Hong Kong. The participants completed a set of questionnaires on executive functions and mental health and provided blood samples for measurement of IL-6 and IL-10 levels during a health assessment session. / Results: Compared with the unexposed group, the exposed group reported poorer maternal care during childhood (β = −4.64, p < 0.001) and had lower family support (β = −2.97, p = 0.010) and higher inflammatory responses (IL-6: β = 0.15, p = 0.001; IL-10: β = 0.11, p = 0.011) at follow-up. Additionally, the associations of childhood maltreatment exposure with family support and maternal care differed by age of onset and the length of time since exposure. / Conclusions: This matched cohort study highlights childhood maltreatment as a risk factor for systemic inflammation and an indicator of suboptimal social environment, both of which could persist over a long period of time

Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study.

OBJECTIVE: Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy. DESIGNS: This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure. RESULT: Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years. CONCLUSION: Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy

Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin.

IMPORTANCE: There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events. OBJECTIVE: To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events. DESIGN, SETTING, AND PARTICIPANTS: A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin. MAIN OUTCOMES AND MEASURES: The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression. RESULTS: Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis. CONCLUSIONS AND RELEVANCE: This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin

Effects of Helicobacter pylori Treatment on Incidence of Gastric Cancer in Older Individuals.

BACKGROUND & AIMS: Although eradication of Helicobacter pylori infection reduces the risk of gastric cancer, few data are available on its effects in older subjects. We compared the age-specific risk of gastric cancer in a large cohort of subjects who received H pylori eradication therapy vs a matched general population. METHODS: We searched the Hospital Authority database of Hong Kong to identify individuals with H pylori infection who had received a course of clarithromycin-containing eradication therapy from January 2003 through December 2012. We compared the gastric cancer incidence in this cohort with the expected incidence for the local general population by retrieving the gastric cancer incidence of the age- and sex-matched population from 2003 through 2014 (the latest available year) from the Hong Kong Cancer Registry. The primary outcome was the incidence of gastric cancer development in the cohort treated for H pylori infection vs the expected number of gastric cancer cases in the general population. Analyses were conducted by a priori age groups of less than 40 years, 40-59 years, and 60 years or older. RESULTS: Among 73,237 subjects infected with H pylori who received eradication therapy, 200 (0.27%) developed gastric cancer during a median follow-up time of 7.6 years. Compared with the matched general population, the gastric cancer risk was significantly lower in subjects 60 years or older who had received H pylori treatment (standardized incidence ratio [SIR], 0.82; 95% confidence interval [CI], 0.69-0.97; P = .02) but not in younger groups. When data were stratified based on time from H pylori treatment (less than 5 years, 5-9 years, and 10 or more years), the risk of gastric cancer was significantly lower than the general population 10 or more years after eradication in the group 40-59 years old (SIR 0.32; 95% CI, 0.08-0.88; P = .04) and the group 60 years or older (SIR, 0.42; 95% CI, 0.42-0.84; P = .02) than the other age groups. CONCLUSIONS: In an analysis of data from a public hospital database on Hong Kong, we associated treatment of H pylori infection with a lower risk of gastric cancer, particularly in older subjects, 10 or more years after treatment

Thromboembolic, bleeding, and mortality risks among patients with nonvalvular atrial fibrillation treated with dual antiplatelet therapy versus oral anticoagulants: A population-based study.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is used for stroke prevention in patients with atrial fibrillation (AF) who refuse to take use oral anticoagulants (OACs). However, clinical data comparing these treatments are limited. OBJECTIVE: The purpose of this study was to compare the clinical outcomes between DAPT and OAC in patients with AF. METHODS: A cohort study using a population-wide database of the Hong Kong Hospital Authority was performed. New patients with AF from 2010-2014 who were prescribed DAPT or OAC (warfarin or dabigatran) were followed until July 31, 2016. Outcomes were thromboembolism, bleeding, and death. Propensity score (PS) matching at a ratio of 1:2 was used to select DAPT users with characteristics similar to those of OAC users, analyzed using Poisson regression. RESULTS: Among 51,946 new patients with AF, 8520 users of OAC and DAPT were identified. The likelihood of receiving DAPT over OAC increased with older age and previous intracranial hemorrhage. Among DAPT users, the incidences of thromboembolism, death, and bleeding per 100 patient-years were 15.8, 17.6, and 5.1, respectively. Compared to DAPT users, PS-matched analysis indicated a lower incidence of thromboembolism and/or death among OAC users (dabigatran: incidence rate ratio [IRR] 0.32; 95% confidence interval [CI] 0.19-0.55; warfarin: IRR 0.58; 95% CI 0.36-0.95), with no significant differences in bleeding events. CONCLUSION: DAPT users were at markedly increased risk for thromboembolism and death compared to OAC users. These findings indicate the need for improved stroke risk reduction strategies among patients taking DAPT and the opportunities for using OAC in high-risk groups to prevent additional events

Contribution of discourse and morphosyntax skills to reading comprehension in Chinese dyslexic and typically developing children

This study aimed at identifying important skills for reading comprehension in Chinese dyslexic children and their typically developing counterparts matched on age (CA controls) or reading level (RL controls). The children were assessed on Chinese reading comprehension, cognitive, and reading-related skills. Results showed that the dyslexic children performed significantly less well than the CA controls but similarly to RL controls in most measures. Results of multiple regression analyses showed that word-level reading-related skills like oral vocabulary and word semantics were found to be strong predictors of reading comprehension among typically developing junior graders and dyslexic readers of senior grades, whereas morphosyntax, a text-level skill, was most predictive for typically developing senior graders. It was concluded that discourse and morphosyntax skills are particularly important for reading comprehension in the non-inflectional and topic-prominent Chinese system

Enhanced recovery program in laparoscopic colectomy for cancer

Introduction: Both laparoscopic colectomy and application of enhanced recovery program (ERP) in open colectomy have been demonstrated to enable early recovery and to shorten hospital stay. This study evaluated the impact of ERP on results of laparoscopic colectomy and comparison was made with the outcomes of patients prior to the application of ERP. Methods: An ERP was implemented in the authors' center in December 2006. Short-term outcomes of consecutive 84 patients who underwent laparoscopic colonic cancer resection 23 months before (control group) and 96 patients who were operated within 13 months; after application of ERP (ERP group) were compared. Results: Between the ERP and control groups, there was no statistical difference in patient characteristics, pathology, operating time, blood loss, conversion rate or complications. Compared to the control group, patients in the ERP group had earlier passage of flatus [2 (range: 1-5) versus 2 (range: 1-4) days after operation respectively; p∈=∈0.03)] and a lower incidence of prolonged post-operative ileus (6% versus 0 respectively; p∈=∈0.02). There was no difference in the hospital stay between the two groups [4 (range: 2-34) days in control group and 4 (range: 2-23) days in ERP group; p∈=∈0.4)]. The re-admission rate was also similar (7% in control group and 5% in ERP group; p∈=∈0.59). Conclusions: In laparoscopic colectomy for cancer, application of ERP was associated with no increase in complication rate but significant improvement of gastrointestinal function. ERP further hastened patient recovery but resulted in no difference in hospital stay. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 31 May 201