Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients. METHODS: We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. RESULTS: A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61 kPa; 95% CI: -1.12, -0.09 kPa), and liver enzymes including alanine transaminase (SMD: -0.86 U/L; 95% CI: -1.16, -0.56 U/L), aspartate transaminase (SMD: -0.87 U/L; 95% CI: -1.22, -0.52 U/L), and gamma-glutamyl transferase (SMD: -0.77 U/L; 95% CI: -1.26, -0.29 U/L). CONCLUSIONS: Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.

Safety, Feasibility, and Acceptability of Telemedicine for Hypertension in Primary Care: A Proof-of-concept and Pilot Randomized Controlled Trial (SATE-HT).

Hypertension (HT) continues to be a leading cause of cardiovascular death and an enormous burden on the healthcare system. Although telemedicine may provide improved blood pressure (BP) monitoring and control, it remains unclear whether it could replace face-to-face consultations in patients with optimal BP control. We hypothesized that an automatic drug refill coupled with a telemedicine system tailored to patients with optimal BP would lead to non-inferior BP control. In this pilot, multicenter, randomized control trial (RCT), participants receiving anti-HT medications were randomly assigned (1:1) to either the telemedicine or usual care group. Patients in the telemedicine group measured and transmitted their home BP readings to the clinic. The medications were refilled without consultation when optimal control (BP < 135/85 mmHg) was confirmed. The primary outcome of this trial was the feasibility of using the telemedicine app. Office and ambulatory BP readings were compared between the two groups at the study endpoint. Acceptability was assessed through interviews with the telemedicine study participants. Overall, 49 participants were recruited in 6 months and retention rate was 98%. Participants from both groups had similar BP control (daytime systolic BP: 128.2 versus 126.9 mmHg [telemedicine vs. usual care], p = 0.41) and no adverse events. Participants in the telemedicine group had fewer general outpatient clinic attendances (0.8 vs. 2, p < 0.001). Interviewees reported that the system was convenient, timesaving, cost saving, and educational. The system could be safely used. However, the results must be verified in an adequately powered RCT. Trial registration: NCT04542564.

Evaluation of Digital Drawing Tests and Paper-and-Pencil Drawing Tests for the Screening of Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-analysis of Diagnostic Studies.

Digital drawing tests have been proposed for cognitive screening over the past decade. However, the diagnostic performance is still to clarify. The objective of this study was to evaluate the diagnostic performance among different types of digital and paper-and-pencil drawing tests in the screening of mild cognitive impairment (MCI) and dementia. Diagnostic studies evaluating digital or paper-and-pencil drawing tests for the screening of MCI or dementia were identified from OVID databases, included Embase, MEDLINE, CINAHL, and PsycINFO. Studies evaluated any type of drawing tests for the screening of MCI or dementia and compared with healthy controls. This study was performed according to PRISMA and the guidelines proposed by the Cochrane Diagnostic Test Accuracy Working Group. A bivariate random-effects model was used to compare the diagnostic performance of these drawing tests and presented with a summary receiver-operating characteristic curve. The primary outcome was the diagnostic performance of clock drawing test (CDT). Other types of drawing tests were the secondary outcomes. A total of 90 studies with 22,567 participants were included. In the screening of MCI, the pooled sensitivity and specificity of the digital CDT was 0.86 (95% CI = 0.75 to 0.92) and 0.92 (95% CI = 0.69 to 0.98), respectively. For the paper-and-pencil CDT, the pooled sensitivity and specificity of brief scoring method was 0.63 (95% CI = 0.49 to 0.75) and 0.77 (95% CI = 0.68 to 0.84), and detailed scoring method was 0.63 (95% CI = 0.56 to 0.71) and 0.72 (95% CI = 0.65 to 0.78). In the screening of dementia, the pooled sensitivity and specificity of the digital CDT was 0.83 (95% CI = 0.72 to 0.90) and 0.87 (95% CI = 0.79 to 0.92). The performances of the digital and paper-and-pencil pentagon drawing tests were comparable in the screening of dementia. The digital CDT demonstrated better diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable performance with paper-and-pencil formats. Therefore, digital drawing tests can be used as an alternative tool for the screening of MCI and dementia.

Cost-effectiveness of pharmacological therapies for people with Alzheimer's disease and other dementias: a systematic review and meta-analysis.

OBJECTIVES: This study aims to synthesize the empirical economic evidence of pharmaceutical therapies for people with dementia. STUDY DESIGN: Systematic review and meta-analysis. Literature evaluating the costs and effects of drug therapies for dementia was indexed until December 2021. Quality of study was assessed using the Cochrane Risk of Bias Tool and Consensus on Health Economic Criteria list. Cost data were standardized to 2020 US dollars and analyzed from healthcare service and societal perspectives. Random-effects models were used to synthesize economic and clinical data, based on mean differences (MDs) and standardized MDs. RESULTS: Ten unique studies were identified from 11,771 records. Acetylcholinesterase inhibitors (AChEIs) and memantine improved dementia-related symptoms, alongside nonsignificant savings in societal cost (AChEIs: MD-2002 [- 4944 ~ 939]; memantine: MD-6322 [- 14355 ~ 1711]). Despite decreases in cost, antidepressants of mirtazapine and sertraline and second-generation antipsychotics were limited by their significant side effects on patients' cognitive and activity functions. Subgroup analysis indicated that the impacts of AChEIs on cost were affected by different analytical perspectives, follow-up periods, and participant age. CONCLUSIONS: AChEIs and memantine are cost-effective with improvements in dementia-related symptoms and trends of cost-savings. More empirical evidence with non-industrial sponsorships and rigorous design in different settings is warranted.

Comparing drawing under instructions with image copying for mild cognitive impairment (MCI) or dementia screening: a meta-analysis of 92 diagnostic studies.

OBJECTIVES: Drawing is a major component of cognitive screening for dementia. It can be performed without language restriction. Drawing pictures under instructions and copying images are different screening approaches. The objective of this study was to compare the diagnostic performance between drawing under instructions and image copying for MCI and dementia screening. METHOD: A literature search was carried out in the OVID databases with keywords related to drawing for cognitive screening. Study quality and risk of bias were assessed by QUADAS-2. The level of diagnostic accuracy across different drawing tests was pooled by bivariate analysis in a random effects model. The area under the hierarchical summary receiver-operating characteristic curve (AUC) was constructed to summarize the diagnostic performance. RESULTS: Ninety-two studies with sample size of 22,085 were included. The pooled results for drawing under instructions showed a sensitivity of 79% (95% CI: 76 - 83%) and a specificity of 80% (95% CI: 77 - 83%) with AUC of 0.87 (95% CI: 0.83 - 0.89). The pooled results for image copying showed a sensitivity of 71% (95% CI: 62 - 79%) and a specificity of 83% (95% CI: 72 - 90%) with AUC of 0.83 (95% CI: 0.80 - 0.86). Clock-drawing test was the screening test used in the majority of studies. CONCLUSION: Drawing under instructions showed a similar diagnostic performance when compared with image copying for cognitive screening and the administration of image copying is relatively simpler. Self-screening for dementia is feasible to be done at home in the near future.

Antihypertensive treatments and risks of lung Cancer: a large population-based cohort study in Hong Kong.

BACKGROUND: There is a growing concern that the use of anti-hypertensives may be associated with an increased risk of cancer, but it remains uncertain for the association between anti-hypertensives and lung cancer risk, as well as their interaction with aspirin in chemoprotective effects. METHODS: The goal of this study is to assess the association between anti-hypertensives use and the risk of lung cancer, as well as the chemopreventive impacts from the combination usage of aspirin and anti-hypertensives. A retrospective cohort study was conducted based on all the public hospital electronic medical records in Hong Kong. Patients with prescription records of anti-hypertensives (ACEi/ARB, CCB, ß-blocker,α-blocker) and/or aspirin were included as the exposure groups. Using the Cox proportional hazards model with inverse probability weighting, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer risk from anti-hypertensives usage or combination usage of aspirin with anti-hypertensives. The likelihood ratio test and interaction model were adopted for exploring the interaction effects with aspirin. RESULTS: A total of 6592 and 84,116 lung cancer cases were identified from the groups of anti-hypertensives users and anti-hypertensives users with aspirin, respectively. The group of non-aspirin patients who received anti-hypertensives showed a significantly lower risk of lung cancer (HR: 0.63, 95% CI: 0.60-0.66), compared to those without anti-hypertensives. When aspirin and α-blocker were used simultaneously, it could lower the risk of lung cancer significantly (HR: 0.53, 95% CI: 0.34-0.84). Moreover, the lower risk of lung cancer persisted with a longer follow-up period of anti-hypertensives usage. Combination usage with aspirin in the users of ACEi/ARB, CCB, and α-blocker showed significant interaction effects. However, the smoking effect could not be eliminated in this analysis. DISCUSSION: Anti-hypertensive treatment was associated with a lower risk of lung cancer, which is associated with the anti-hypertensives exposure period. The potential interaction on the chemopreventive influence from combination usage of α-blocker and aspirin might exist. More corroborations on these findings are needed to focus on the different settings in future studies.

Supporting Informal Caregivers of People With Dementia in Cost-Effective Ways: A Systematic Review and Meta-Analysis.

OBJECTIVES: Caring for persons with dementia is a heavy burden for informal caregivers. This study aimed to appraise the economic evidence of interventions supporting informal caregivers of people with dementia. METHODS: Literature was searched, and trial-based studies evaluating the costs and effects of interventions supporting informal caregivers of people with dementia were included. Cost data were analyzed from both healthcare and societal perspectives. Random-effects models were used to synthesize cost and effect data, based on mean differences (MDs) or standardized MDs. RESULTS: Of 33 eligible studies identified from 48 588 records, 14 (42.4%) showed net savings in total cost regardless of analytical perspectives. Among 22 studies included in meta-analyses, caregiver-focused psychosocial interventions showed improvements in caregivers' psychological health (n = 4; standardized MD 0.240; 95% confidence interval 0.094-0.387); nevertheless, the increases in societal cost were significant (n = 5; MD 3144; 95% confidence interval 922-5366). Psychological intervention and behavioral management engaging patient-caregiver dyads showed positive effects on caregivers' subjective burden, also with increases in total cost. Subgroup analyses indicated that the inclusion of different intervention components, the caregiver characteristics, and the follow-up periods could affect the costs and effects of interventions supporting informal caregivers. CONCLUSIONS: Psychosocial interventions directed at informal caregivers and dyad-based psychological and behavioral interventions are effective but also expensive. The use of these interventions depends on the society's willingness to pay. More comprehensive economic evidence of interventions supporting informal caregivers is required, and the design of intervention should focus more on different intervention components, characteristics of patients and caregivers, and healthcare systems.

Diagnostic accuracy of dementia screening tools in the Chinese population: a systematic review and meta-analysis of 167 diagnostic studies.

BACKGROUND: The rate of undetected dementia is high in China. However, the performance of dementia screening tools may differ in the Chinese population due to the lower education level and cultural diversity. This study aimed to evaluate the diagnostic accuracy of dementia screening tools in the Chinese population. METHODS: Eleven electronic databases were searched for studies evaluating the diagnostic accuracy of dementia screening tools in older Chinese adults. The overall diagnostic accuracy was estimated using bivariate random-effects models, and the area under the summary receiver operating characteristic curve was presented. RESULTS: One hundred sixty-seven studies including 81 screening tools were identified. Only 134 studies qualified for the meta-analysis. The Mini-Mental State Examination (MMSE) was the most commonly studied tool, with a combined sensitivity (SENS) and specificity (SPEC) of 0.87 (95%CI 0.85-0.90) and 0.89 (95%CI 0.86-0.91), respectively. The Addenbrooke's Cognitive Examination-Revised (ACE-R) (SENS: 0.96, 95%CI 0.89-0.99; SPEC: 0.96, 95%CI 0.89-0.98) and Montreal Cognitive Assessment (MoCA) (SENS: 0.93, 95%CI 0.88-0.96; SPEC: 0.90, 95%CI 0.86-0.93) showed the highest performance. The General Practitioner Assessment of Cognition (GPCOG), Hasegawa's Dementia Scale and Cognitive Abilities Screening Instrument had performances comparable to that of the MMSE. The cut-off scores ranged widely across studies, especially for the MMSE (range: 15-27) and MoCA (range: 14-26). CONCLUSIONS: A number of dementia screening tools were validated in the Chinese population after cultural and linguistical adaptations. The ACE-R and MoCA had the best diagnostic accuracy, whereas the GPCOG, with an administration time < 5 minutes, could be considered as a rapid screening tool.

The role of body mass index in the association between dietary sodium intake and blood pressure: A mediation analysis with NHANES.

BACKGROUND AND AIMS: Recent research demonstrated that obesity and high dietary sodium intake, the two established risk factors for hypertension, were associated with each other. The objective was to investigate the potential indirect effect of sodium intake on blood pressure via body mass index (BMI). METHODS AND RESULTS: Using ten years data from US NHANES (2007-2016), the study included adult participants (>20 years old) who were not taking antihypertensive medications and without baseline diseases (n = 12,262). BMI was modelled as the mediator of sodium intake on systolic and diastolic blood pressure, adjusted for age, sex, socioeconomic status, smoking, drinking, physical activity, calorie intake, fluid intake and potassium intake. Mediation analysis was performed to evaluate total effect, direct effect and indirect effect via BMI. Subgroup analyses based on three age subgroups (20-40, 41-60 and ≥61 years old) were performed. The mean age was 39.29 (13.4) years and 53.1 (0.45) % were males. The mean BMI was 27.8 (6.20) kg/m2. Overall, 1 g/d increase in sodium intake was associated with an increased systolic blood pressure by 0.36 (95% confidence interval 0.14 to 0.58) mmHg, with a direct effect (0.14 (0.09-0.19)) and an indirect effect via BMI (0.23 (0.02-0.44)). The indirect effect was mainly observed in participants ≤60 years old. CONCLUSION: Sodium intake showed both direct effect and indirect effect (via BMI) on systolic blood pressure in US NHANES. The findings provide evidence for combining sodium restriction and weight reduction measures for prevention of hypertension. Cautions should be taken when generalizing the findings to other populations with lower average BMI.

Correction: Electronic Cognitive Screen Technology for Screening Older Adults With Dementia and Mild Cognitive Impairment in a Community Setting: Development and Validation Study.

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Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, but they are associated with a number of serious adverse effects, including hypertension, cardiovascular disease, kidney injury and GI complications. OBJECTIVE: To develop a set of multidisciplinary recommendations for the safe prescription of NSAIDs. METHODS: Randomised control trials and observational studies published before January 2018 were reviewed, with 329 papers included for the synthesis of evidence-based recommendations. RESULTS: Whenever possible, a NSAID should be avoided in patients with treatment-resistant hypertension, high risk of cardiovascular disease and severe chronic kidney disease (CKD). Before treatment with a NSAID is started, blood pressure should be measured, unrecognised CKD should be screened in high risk cases, and unexplained iron-deficiency anaemia should be investigated. For patients with high cardiovascular risk, and if NSAID treatment cannot be avoided, naproxen or celecoxib are preferred. For patients with a moderate risk of peptic ulcer disease, monotherapy with a non-selective NSAID plus a proton pump inhibitor (PPI), or a selective cyclo-oxygenase-2 (COX-2) inhibitor should be used; for those with a high risk of peptic ulcer disease, a selective COX-2 inhibitor plus PPI are needed. For patients with pre-existing hypertension receiving renin-angiotensin system blockers, empirical addition (or increase in the dose) of an antihypertensive agent of a different class should be considered. Blood pressure and renal function should be monitored in most cases. CONCLUSION: NSAIDs are a valuable armamentarium in clinical medicine, but appropriate recognition of high-risk cases, selection of a specific agent, choice of ulcer prophylaxis and monitoring after therapy are necessary to minimise the risk of adverse events.

Effects of virtual reality on moods in community older adults. A multicenter randomized controlled trial.

INTRODUCTION: Virtual reality (VR) technology is a potential method to use in cognitive intervention, but the use of VR in cognitive stimulation intervention for older adults has not been investigated. Therefore, the aim of this study was to investigate the mood change of older adults after participating in the VR cognitive stimulation activity. METHODS: This is a multicenter randomized controlled, cross-over trial. The intervention was a VR cognitive stimulation activity, and the control was a paper-and-pencil activity. The participants were older adults with age over 60 and recruited in the elderly community centers. The Positive and Negative Affect Score (PANAS) was used to measure mood change. Mean difference (MD) with 95% confidence interval (95% CI) was calculated. The Simulator sickness questionnaire was used to measure adverse events. RESULTS: A total of 236 participants from 19 community centers were recruited. After the VR activity, the participants had a significant increase in total PANAS positive affect score (MD = 2.09, 95% CI = 0.69 to 3.49), and a significant reduction in total negative affect score (MD = -1.99, 95% CI = -2.55 to -1.43). The reduction in negative affect score was significantly larger in VR activity than paper-and-pencil activity (MD = -0.48, 95% CI = -0.98 to 0.00). Besides, only three participants reported severe advance events after VR activity. CONCLUSIONS: The use of VR technology is well accepted by older adults. Therefore, the use of VR technology through smartphone and a mobile app can be a potential method for future cognitive training interventions.

Cognitive training interventions and depression in mild cognitive impairment and dementia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Depression is common in people with cognitive impairment but the effect of cognitive training in the reduction of depression is still uncertain. AIMS: The purpose of this paper is to evaluate the effect of cognitive training interventions in the reduction of depression rating scale score in people with cognitive impairment. METHODS: Literature searches were conducted via OVID databases. Randomized controlled trials (RCTs) evaluated the effect of cognitive training interventions for the reduction of depression rating scale score in people with mild cognitive impairment (MCI) or dementia were included. Mean difference (MD) with 95% confidence interval (CI) was used to combine the results of Geriatric Depression Scale (GDS). Standardized mean difference (SMD) was used to combine the results of different depression rating scales. Subgroup analyses were conducted according to the types of cognitive training and severity of cognitive impairment, i.e. MCI and dementia. RESULTS: A total of 2551 people with MCI or dementia were extracted from 36 RCTs. The baseline mean score of GDS-15 was 4.83. Participants received cognitive training interventions had a significant decrease in depression rating scale score than the control group (MD of GDS-15 = -1.30, 95% CI = -2.14--0.47; and SMD of eight depression scales was -0.54 (95% CI = -0.77--0.31). In subgroup analyses, the effect size of computerized cognitive training and cognitive stimulation therapy were medium-to-large and statistically significant in the reduction of depression rating scale score. CONCLUSIONS: Cognitive training interventions show to be a potential treatment to ameliorate depression in people with cognitive impairment.

Electronic Cognitive Screen Technology for Screening Older Adults With Dementia and Mild Cognitive Impairment in a Community Setting: Development and Validation Study.

BACKGROUND: A digital cognitive test can be a useful and quick tool for the screening of cognitive impairment. Previous studies have shown that the diagnostic performance of digital cognitive tests is comparable with that of conventional paper-and-pencil tests. However, the use of commercially available digital cognitive tests is not common in Hong Kong, which may be due to the high cost of the tests and the language barrier. Thus, we developed a brief and user-friendly digital cognitive test called the Electronic Cognitive Screen (EC-Screen) for the detection of mild cognitive impairment (MCI) and dementia of older adults. OBJECTIVE: The aim of this study was to evaluate the performance of the EC-Screen for the detection of MCI and dementia in older adults. METHODS: The EC-Screen is a brief digital cognitive test that has been adapted from the Rapid Cognitive Screen test. The EC-Screen uses a cloud-based platform and runs on a tablet. Participants with MCI, dementia, and cognitively healthy controls were recruited from research clinics and the community. The outcomes were the performance of the EC-Screen in distinguishing participants with MCI and dementia from controls, and in distinguishing participants with dementia from those with MCI and controls. The cohort was randomly split into derivation and validation cohorts based on the participants' disease group. In the derivation cohort, the regression-derived score of the EC-Screen was calculated using binomial logistic regression. Two predictive models were produced. The first model was used to distinguish participants with MCI and dementia from controls, and the second model was used to distinguish participants with dementia from those with MCI and controls. Receiver operating characteristic curves were constructed and the areas under the curves (AUCs) were calculated. The performances of the two predictive models were tested using the validation cohorts. The relationship between the EC-Screen and paper-and-pencil Montreal Cognitive Assessment-Hong Kong version (HK-MoCA) was evaluated by the Pearson correlation coefficient. RESULTS: A total of 126 controls, 54 participants with MCI, and 63 participants with dementia were included in the study. In differentiating participants with MCI and dementia from controls, the AUC of the EC-Screen in the derivation and validation cohorts was 0.87 and 0.84, respectively. The optimal sensitivity and specificity in the derivation cohorts were 0.81 and 0.80, respectively. In differentiating participants with dementia from those with MCI and controls, the AUC of the derivation and validation cohorts was 0.90 and 0.88, respectively. The optimal sensitivity and specificity in the derivation cohort were 0.83 and 0.83, respectively. There was a significant correlation between the EC-Screen and HK-MoCA (r=-0.67, P<.001). CONCLUSIONS: The EC-Screen is suggested to be a promising tool for the detection of MCI and dementia. This test can be self-administered or assisted by a nonprofessional staff or family member. Therefore, the EC-Screen can be a useful tool for case finding in primary health care and community settings.

Acceptance Prediction for Answers on Online Health-care Community.

BACKGROUND: With the development of e-Health, it plays a more and more important role in predicting whether a doctor's answer can be accepted by a patient through online healthcare community. Unlike the previous work which focus mainly on the numerical feature, in our framework, we combine both numerical and textual information to predict the acceptance of answers. The textual information is composed of questions posted by the patients and answers posted by the doctors. To extract the textual features from them, we first trained a sentence encoder to encode a pair of question and answer into a co-dependent representation on a held-out dataset. After that,we can use it to predict the acceptance of answers by doctors. RESULTS: Our experimental results on the real-world dataset demonstrate that by applying our model additional features from text can be extracted and the prediction can be more accurate. That's to say, the model which take both textual features and numerical features as input performs significantly better than model which takes numerical features only on all the four metrics (Accuracy, AUC, F1-score and Recall). CONCLUSIONS: This work proposes a generic framework combining numerical features and textual features for acceptance prediction, where textual features are extracted from text based on deep learning methods firstly and can be used to achieve a better prediction results.

Long-term use of low-dose aspirin for cancer prevention: A 10-year population cohort study in Hong Kong.

Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, has been found to possess protective effects against cancer development in the Western populations. Such effects among Asian populations remain uncertain. The objective of this study is to investigate the use of aspirin on prevention of different cancers among Chinese users. This population-based study utilized database from the Hong Kong Hospital Authority; adults with aspirin prescription for at least 6 months between 2000 and 2004 were included and followed up until 2013. Aspirin users were age-sex matched with non-aspirin users at a 1:2 ratio. Incidences of cancer were the primary outcome measured by relative risk (RR). A total of 204,170 aspirin users and 408,339 non-aspirin users were included, with the mean age 67.5 years, 7.7 years average duration of aspirin prescription and 80 mg as the median dose of aspirin. Cancer incidences were found in 26,929 (13.2%) aspirin users and 70,755 (17.3%) non-aspirin users. Compared with patients who had not been prescribed aspirin, aspirin usage led to significant reduction of cancers in liver (RR: 0.49), stomach (RR: 0.42), colorectum (RR: 0.71), lung (RR: 0.65), pancreas (RR: 0.54), oesophagus (RR: 0.59) and leukaemia (RR: 0.67). There was no demonstrable reduction of kidney cancer, bladder cancer, prostate cancer and multiple myeloma in association with the usage of aspirin. Risk of breast cancer was shown to marginally increase (RR: 1.14) with aspirin usage. This study demonstrated that the long-term use of low-dose aspirin is associated with the reduction in risk of various cancers but not for breast cancer. Further investigation is needed before promoting aspirin as a primary chemoprotective agent.

Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer.

BACKGROUND & AIMS: Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC. METHODS: We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups. RESULTS: The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio [HR] = 3.85, 95% CI = 2.62-5.64, P = 5.5 × 10-12) or Streptococcus gallolyticus (HR = 5.73, 95% CI = 2.18-15.1, P = 4.1 × 10-4) compared with the unexposed group. In addition, the risk of CRC was increased in patients with bacteremia from Fusobacterium nucleatum (HR = 6.89, 95% CI = 1.70-27.9, P = .007), Peptostreptococcus species (HR = 3.06, 95% CI = 1.47-6.35, P = .003), Clostridium septicum (HR = 17.1, 95% CI = 1.82-160, P = .013), Clostridium perfringens (HR = 2.29, 95% CI = 1.16-4.52, P = .017), or Gemella morbillorum (HR = 15.2, 95% CI = 1.54-150, P = .020). We observed no increased risk in patients with bacteremia caused by microbes not previously associated with colorectal neoplasms. CONCLUSIONS: In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.

Low-dose aspirin can reduce colorectal cancer mortality after surgery: A 10-year follow-up of 13 528 colorectal cancer patients.

BACKGROUND AND AIM: The chemopreventive effect of aspirin in colorectal cancer (CRC) is well studied, but its benefit in patients after CRC diagnosis and surgery is unclear. This study aims to investigate the effects of low-dose aspirin use in mortality among CRC patients after surgery. METHODS: Patients were analyzed in two cohorts: (i) patients taking aspirin before CRC diagnosis and continued or discontinued aspirin after surgery and (ii) patients, who never used aspirin before CRC diagnosis, received or did not receive aspirin after surgery. CRC-related mortality and all-cause mortality were the primary and secondary outcomes. Sub-distribution hazard ratio (SHR) for competing-risk CRC mortality was fitted to adjust for other causes of death; hazard ratio (HR) was used to compare all-cause mortality. RESULTS: A total of 13 528 CRC patients were included. Among 3292 patients with regular aspirin use before CRC diagnosis, 2658 (80.7%) continued aspirin and 634 (19.3%) discontinued aspirin after surgery. Continuous use of aspirin significantly reduced CRC-related mortality (SHR: 0.69, 95% confidence interval [CI]: 0.59-0.81) and all-cause mortality (HR: 0.61, 95% CI: 0.55-0.68). Among 10 236 patients who did not use aspirin before CRC diagnosis, 1054 patients (10.3%) received aspirin after surgery and 9182 (89.7%) did not. Aspirin initiated after surgery reduced CRC-related mortality (SHR: 0.88, 95% CI: 0.80-0.98) and all-cause mortality (HR: 0.87, 95% CI: 0.81-0.94). CONCLUSIONS: Irrespective of aspirin use before surgery for CRC, low-dose aspirin after surgery lowers risk of both CRC-related mortality and overall mortality.

Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

Risk of gastrointestinal bleeding and benefit from colorectal cancer reduction from long-term use of low-dose aspirin: A retrospective study of 612 509 patients.

BACKGROUND AND AIM: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well known to protect against development of colorectal cancer (CRC) but increases risk of gastrointestinal bleeding (GIB). This cohort study aims to evaluate the benefit of low-dose aspirin to prevent CRC and its associated risk of GIB. METHOD: A population-based dataset was used to compare incidence and mortality of CRC and GIB among patients receiving low-dose aspirin with sex-matched and age-matched controls (1:2). A total of 204 170 aspirin users taking aspirin for at least 6 months and 408 339 nonusers were analyzed. Patients' clinical outcomes were documented for up to 14 years or until death. RESULTS: A total of 612 509 patients were included; 5118 (2.51%) out of 204 170 aspirin users were diagnosed with CRC; and 2073 (1.02%) died of the malignancy. On the other hand, 13 336 (3.27%) out of 408 339 non-aspirin users were diagnosed with CRC, and 6953 (1.70%) died. Using the competing risk regression, aspirin usage significantly reduced CRC mortality (subdistribution hazard ratio = 0.59; 95% confidence interval = 0.56 to 0.62). A total of 9483 (4.64%) aspirin users developed GIB, and 820 (0.40%) died, while 11 198 (2.74%) nonusers developed GIB, and 1488 (0.36%) died. Aspirin usage marginally increased risk of bleeding-related mortality (subdistribution hazard ratio = 1.09; 95% confidence interval = 1.00 to 1.19). Subgroup analyses showed the use of acid-secreting agents significantly reduced aspirin-induced mortality. CONCLUSION: The long-term use of aspirin reduces both incidence and mortality of CRC and at the same time increases incidence and mortality risk of GIB. With combination use of acid-secreting agents, the bleeding risk can be reduced.