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BACKGROUND: The use of intravenous (IV) proton pump inhibitors (PPI) before an endoscopy in upper-GI bleeding (UGIB) was shown to reduce the need of endoscopic therapy and shorten hospital stay. OBJECTIVE: To investigate whether preemptive use of a PPI in UGIB is a cost-effective strategy. DESIGN: A decision analysis model that represents treatment pathways for patients with UGIB was constructed and structuralized by 30-day outcomes. Direct costs of medical treatment, diagnostic and therapeutic endoscopy, endoscopic re-treatment, surgery, and hospitalization were analyzed. SETTING: Prince of Wales Hospital, Hong Kong. PATIENTS: A total of 631 patients were recruited. Sixty patients (19.1%) in the PPI group and 90 patients (28.4%) in the placebo group required endoscopic hemostasis at index endoscopy. MAIN OUTCOME MEASUREMENTS: The primary measurements were cost-effectiveness ratios and incremental cost-effectiveness ratios (ICER) to avert endoscopic therapy between PPI and placebo treatment. Sensitivity analyses were conducted by varying the cost of endoscopy, hospitalization, the incidence rate of endoscopic therapy, and the proportion of bleeding peptic ulcers. RESULTS: The overall direct cost per patient was U.S. dollars (USD) $2813 for PPI treatment and USD $2948 for the placebo. A PPI reduced endoscopic therapy by 7.4% and resulted in a lower cost-effectiveness ratio per endoscopic therapy averted (USD $3561) than the placebo (USD $4117). The ICER value was USD -$1843, which indicated that preemptive PPI treatment is more effective and less costly for UGIB. When the proportions of patients with peptic ulcer bleeding were greater than 8.3%, the preemptive PPI treatment remained cost saving. CONCLUSIONS: Preemptive use of IV PPI before an endoscopy is a cost-effective strategy in the management of UGIB. [ABSTRACT FROM AUTHOR]

Background: Memory complaints are the early symptoms of cognitive impairment, and they usually bring anxiety about cognitive deterioration among the elderly population. Musical interventions were demonstrated to relieve dementia symptoms. This pilot study investigated the potential benefits of rhythmic musical intervention, African drumming, on cognitive function and mood status with traditional and digital assessments for elderly participants., Method: Participants were recruited through social media. The musical intervention was arranged by drumming instructors certified by the Hong Kong Association of African Drumming. Participants joined regular training classes with eight lessons, which covered rhythmic clapping and drumming, power control, and overall performance with songs. The inclusion criteria included the following: (1) age over 50; (2) self-reported complaints of memory loss; (3) the ability to use digital devices, such as a smartphone; and (4) can understand the content of questionnaires and follow the intervention schedules. Those with hearing impairment, failure to use Chinese, and active psychosis or dementia were excluded. Cognitive function was measured by the Hong Kong version of the Montreal Cognitive Assessment (HK-MoCA) and a digital platform, ScreenMat. Anxiety and depression levels were assessed by the State-Trait Anxiety Inventory (STAI) and Geriatric Depression Scale (GDS-15). All assessments were performed before and after the drumming classes. The outcomes were compared using the Wilcoxon signed rank test with 0.05 as the significance level., Result: Twenty-two participants joined this study with an attendance rate of 90%. The overall cognitive function of the participants was good with an average score of 27 for HK-MoCA. After eight sessions of African drum intervention, the cognitive function did not show a significant improvement, but the response time of answering the digital cognitive questions was significantly faster than before the intervention (-39.9 s, p  = 0.03). The response time for the short-term memory function was most significantly reduced (-13.5 s, p  = 0.017). The anxiety and depression scores (i.e. STAI and GDS) also significantly improved ( p  < 0.001) after the intervention., Conclusion: Rhythmic musical intervention is not only effective in improving emotional status, but also potentially good for improving cognitive symptoms, including the response time of the memory test. Digital behavioral analysis may bring new insights for future research on cognitive assessment., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Post-traumatic stress disorder (PTSD) frequently follows neurological disorders such as non-traumatic subarachnoid hemorrhage (SAH) and has debilitating consequences., Objective: The aim of this systematic review was the critical appraisal of the literature on the frequency, severity, and temporal progression of PTSD in patients with SAH, the etiology of PTSD, and its effect on patients' quality of life (QoL)., Material and Methods: Studies were obtained from three databases: PubMed EMBASE, PsycINFO, and Ovid Nursing. The inclusion criteria were English-language studies on adults (defined as at least 18 years of age) in which ≥10 of the participants received a diagnosis of PTSD following SAH. Applying these criteria, 17 studies (N = 1,381) were included., Results: Between 1% and 74% of the participants in each study had PTSD, with a weighted average of 36.6% across all studies. Post-SAH PTSD showed significant correlations with premorbid psychiatric disorders, neuroticism, and maladaptive coping styles. The risk of PTSD was also higher in participants with comorbid depression and anxiety. Stress related to post-ictal events and fear of recurrence were associated with PTSD. However, the risk of PTSD was lower in participants with effective social support networks. The participants' QoL was negatively affected by PTSD., Conclusions: This review highlights the high occurrence of PTSD in SAH patients. The temporal progression and chronicity of post-SAH PTSD warrant further research, as do its neuroanatomical and neurochemical correlates. We call for more randomized controlled trials investigating these aspects., Competing Interests: None

Background: Post-traumatic stress disorder (PTSD) is a common and debilitating illness that accompanies many neurological disorders, including stroke., Objective: The aim of this systematic review was to identify and critically appraise all published studies that have reported the frequency, severity, and time course of PTSD after stroke, the factors associated with its development, and its impact on patients' lives., Material and Methods: The PubMed EMBASE, PsycINFO, and Ovid Nursing databases were searched for studies published in English that had recruited at least 10 patients (>18 years old) after stroke and who were also diagnosed with PTSD., Results: Twenty studies covering a total of 1785 patients met the study inclusion criteria. The frequency of PTSD ranged from 3% to 31%, with a weighted proportion of 16.5%. PTSD runs a chronic course. PTSD after stroke was associated with premorbid neuroticism, negative affect, and maladaptive coping styles. Comorbid depression and anxiety also increased the risk of PTSD. Psychological factors such as negative appraisal and perceived high risk of recurrence and distress were associated with PTSD. Good social support reduced the risk of PTSD. PTSD reduced patients' quality of life, physical functioning, and medication compliance., Conclusions: PTSD is common after stroke. Further research is needed to clarify its time course and identify the neurochemical factors and brain circuits associated with the development of post-stroke PTSD. Randomized controlled treatment trials targeting PTSD in stroke are warranted., Competing Interests: None

Osteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual-energy X-ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta-analysis was designed to investigate which HR-pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR-pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta-analysis. HR-pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR-pQCT parameters, our meta-analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR-pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR-pQCT, the non-weight-bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white-based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR-pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

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/m 2 . 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., Competing Interests: Conflicts of interest All authors have non conflict of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: Processed meat and high sodium intake are common in Western diet. The objective was to examine their independent effects on the risk of colorectal cancer (CRC)., Methods: We performed both observational analysis with UK Biobank and genetic analysis with Mendelian randomization (MR). The 24-h urinary sodium (UNa) and reported intake of processed meat were fitted on incident CRC by multivariable Cox proportional hazard model, adjusted for covariates, such as age, gender, family history, etc. Different sodium measures were used for sensitivity analyses. Two-sample MR analyses were performed using summary data from genome-wide association studies of UNa and CRC. Multivariable MR was adjusted for body mass index., Results: We included 415 524 eligible participants from UK Biobank. During a median follow-up of 11.1 years, 2663 participants were diagnosed with CRC. High intake of processed meat independently increased risk of CRC by 23% (HR 1.23; 95% CI: 1.03 to 1.46), but 24-h UNa was not significantly associated with CRC (HR 0.96; 95% CI: 0.87 to 1.06). Furthermore, MR also showed little evidence for the effect of UNa on CRC (OR 1.02; 95% CI: 0.11 to 9.42). Sensitivity analyses showed consistent results across different measurements of sodium intake., Conclusions: Intake of processed meat had an independent effect on the risk of CRC, but the risk was not associated with sodium level. Reduction of processed meat intake may be an effective strategy for CRC prevention, while sodium reduction should still be recommended to achieve other health benefits., Competing Interests: Conflict of Interest None to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: While the chemoprevention effect of aspirin is well-established, the effects of metformin in cancer prevention is still controversial. This study is to investigate the use of aspirin, metformin, or the combination of both is associated with delayed cancer incidence., Method: This dataset is based on the electronic medical record of public hospitals in Hong Kong. Patients were classified into 1. aspirin user, 2. metformin user, 3. both aspirin and metformin user and 4. control group with neither aspirin nor metformin used. Aspirin and/or metformin must have been taken for over 6 months in the treatment group and cancer incidences was counted at least 6 months after exposure to such medications. The primary outcome of this study was overall incidence of cancer during the follow-up period. The secondary outcomes were cancer incidences of specific sites, including colon/rectum, liver, oesophagus, pancreas, stomach, lung, breast, kidney, bladder and prostate. Cox proportional hazards regression models were fitted to estimate hazard ratios of cancer risks. Inverse probability of treatment weighting was used to control for the medication effects., Results: A total of 120,971 aspirin users, 11,365 metformin users, and 6630 aspirin plus metformin users, were identified. Compare to the control groups, those who used aspirin alone demonstrated a significant reduction in overall cancer risk (HR 0.80, 95% CI 0.73-0.87). Similarly, those who used metformin alone also showed an overall reduction in cancer risk (HR 0.79, 95% CI 0.71-0.88). Patients who received both aspirin and metformin showed the most significant reduction in overall cancer risk (HR 0.53, 95% CI 0.45-0.63). Metformin showed a significant reduction in cancer risk of lung, oesophagus and bladder., Conclusion: There is a similar decrease in overall cancer rate with the use of aspirin or metformin alone. A more significant reduction in overall cancer risk was found with the use of both agents., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: A systematic review on the reproducibility of ambulatory blood pressure measurements (ABPM) has not yet been conducted. This meta-analysis compared 24-h/daytime/night-time SBP and DBP mean values and SBP/DBP nocturnal dipping status from ABPMs in participants with or without hypertension., Methods: Ovid MEDLINE, EMBASE, and CINAHL Complete databases were searched for articles published before 3 May 2019. Eligible studies reporting a 24-h ABPM repeated at least once within 1 month were included. The mean daytime/night-time/24-h BP values, percentage of nocturnal dipping, and proportion of nondippers were compared between the first and second day of measurements, and the proportion of participants with inconsistent dipping status were estimated using a random effect model., Results: Population-based analysis found a 0-1.1 mmHg difference between the first and second ABPM for 24-h/daytime/night-time SBP and DBP and 0-0.5% for percentage of SBP/DBP nocturnal dipping. The proportion of non-dippers was not different between the first and second ABPM. Intra-individual analysis found that the 95% limit of agreements (LOA) for SBP/DBP were wide and the 95% LOA for daytime SBP, common reference to diagnose hypertension, ranged -16.7 to 18.4 mmHg. Similarly, 32% of participants had inconsistent nocturnal dipping status., Conclusion: ABPM had excellent reproducibility at the population level, favouring its application for research purposes; but reproducibility of intra-individual BP values and dipping status from a 24-h ABPM was limited. The available evidence was limited by the lack of high-quality studies and lack of studies in non-Western populations.

Background: Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA)., Aim: To evaluate regular use of PPIs and risk of RA., Methods: This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2 years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders., Results: We documented 421 cases of RA over 1 753 879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR = 1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend = 0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with >0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for >4 years' use., Conclusions: Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding., (© 2020 John Wiley & Sons Ltd.)

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.

Memantine and the Acetylcholinesterase inhibitors (AChEIs) are two classes of drugs that are used to treat patients with Alzheimer's disease. We conducted a network meta-analysis of randomized controlled trials to compare the treatment effectiveness of monotherapy or combination therapy A total of 23,707 AD patients in 76 randomized trials were identified. In patients with mild-to-moderate AD, monotherapy with donepezil, galantamine or rivastigmine were superior to placebo in enhancing cognitive functions and activities of daily living (ADL), whereas monotherapy with donepezil or memantine were superior to placebo in improving behavioral symptoms. However, combination therapy with AChEIs and memantine did not show additional benefit than monotherapy. In patients with moderate-to-severe AD, neither monotherapy nor combination therapy were superior to placebo in any domain measurement. Combination therapy with memantine and AChEIs is confirmed to have no additional benefits over monotherapy. This article is protected by copyright. All rights reserved., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

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., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Patients with chronic hepatitis B (CHB) need long-term antiviral treatment with nucleos(t)ide analogues (NA). Animal studies suggest that some NA may increase cancer risk, but human data are lacking., Aim: To investigate cancer risks in patients with or without NA treatment., Methods: We conducted a territory-wide cohort study using the database from Hospital Authority in Hong Kong. The diagnosis of CHB and various malignancies was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes between 2000 and 2012. Patients exposed to any of the oral NA for CHB were included. The primary outcome was incident cancers. A 3-year landmark analysis, with follow-up up to 7 years, was used to evaluate the relative risk of cancers in treated and untreated patients., Results: A total of 44 494 patients (39 712 untreated and 4782 treated) were included in the analysis. During 194 890 patient-years of follow-up, hepatocellular carcinoma developed in 402 (1.0%) untreated patients and 179 (3.7%) treated patients, while other cancers developed in 528 (1.3%) and 128 (2.7%) patients respectively. After propensity score weighting, treated patients had similar risks of all malignancies [weighted hazard ratio (wHR): 1.01, 95% CI: 0.82-1.25, P = 0.899], lung/pleural cancers (wHR: 0.82, 95% CI: 0.52-1.31, P = 0.409) and urinary/renal malignancies (wHR: 1.04, 95% CI: 0.38-2.81, P = 0.944) when compared with untreated patients., Conclusions: Oral nucleos(t)ide analogue treatment does not appear to increase cancer risk in patients with chronic hepatitis B. Given the beneficial effect on liver outcomes, our data support the current practice of long-term anti-viral therapy., (© 2017 John Wiley & Sons Ltd.)

Background Screening for depression in older adults is recommended. Aims To evaluate the diagnostic accuracy of the Two-Question Screen for older adults and compare it with other screening instruments for depression. Method We undertook a literature search for studies assessing the diagnostic performance of depression screening instruments in older adults. Combined diagnostic accuracy including sensitivity and specificity were the primary outcomes. Potential risks of bias and the quality of studies were also assessed. Results A total of 46 506 participants from 132 studies were identified evaluating 16 screening instruments. The majority of studies (63/132) used various versions of the Geriatric Depression Scale (GDS) and 6 used the Two-Question Screen. The combined sensitivity and specificity for the Two-Question Screen were 91.8% (95% CI 85.2-95.6) and 67.7% (95% CI 58.1-76.0), respectively; the diagnostic performance area under the curve (AUC) was 90%. The Two-Question Screen showed comparable performance with other instruments, including clinician-rated scales. The One-Question Screen showed the lowest diagnostic performance with an AUC of 78%. In subgroup analysis, the Two-Question Screen also had good diagnostic performance in screening for major depressive disorder. Conclusions The Two-Question Screen is a simple and short instrument for depression screening. Its diagnostic performance is comparable with other instruments and, therefore, it would be favourable to use it for older adult screening programmes., (© The Royal College of Psychiatrists 2017.)

Background: China is facing the challenges of an expanding ageing population and the impact of rapid urbanization, cancer rates are subsequently increasing. This study focuses on the changes of the ageing population and projects the incidence of common ageing-related cancers in the urban regions in China up to 2030., Sources of Data: Cancer incidence data and population statistics in China were extracted from the International Agency for Research on Cancer., Areas of Agreement: Due to improving longevity in China, continuous and remarkable increasing trends for the lung, colorectal and prostate cancers are expected., Growing Points: The rate of expanding ageing population was taken into account when predicting the trend of cancer incidence; the estimations of ageing-related cancers were more factual and significant than using the conventional approach of age standardization., Areas Timely for Developing Research: The incidence rates of lung, colorectal and prostate cancers will continue to rise in the future decades due to the rise of ageing population. Lifestyle modification such as cutting tobacco smoking rates and promoting healthier diets as well as cancer screening programs should be a health system priority in order to decrease the growing burden of cancer-related mortality and morbidity., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: Well-conducted meta-analyses (MAs) are considered as one of the best sources of clinical evidence for treatment decision. MA with methodological flaws may introduce bias and mislead evidence users. The aim of this study is to investigate the characteristics and methodological quality of MAs on diabetes mellitus (DM) treatments., Design: Systematic review., Methods: Cochrane Database of Systematic Review and Database of Abstract of Reviews of Effects were searched for relevant MAs. Assessing methodological quality of systematic reviews (AMSTAR) tool was used to evaluate the methodological quality of included MAs. Logistic regression analysis was used to identify association between characteristics of MA and AMSTAR results., Results: A total of 252 MAs including 4999 primary studies and 13,577,025 patients were included. Over half of the MAs (65.1%) only included type 2 DM patients and 160 MAs (63.5%) focused on pharmacological treatments. About 89.7% MAs performed comprehensive literature search and 89.3% provided characteristics of included studies. Included MAs generally had poor performance on the remaining AMSTAR items, especially in assessing publication bias (39.3%), providing lists of studies (19.0%) and declaring source of support comprehensively (7.5%). Only 62.7% MAs mentioned about harm of interventions. MAs with corresponding author from Asia performed less well in providing MA protocol than those from Europe., Conclusions: Methodological quality of MA on DM treatments was unsatisfactory. There is considerable room for improvement, especially in assessing publication bias, providing lists of studies and declaring source of support comprehensively. Also, there is an urgent need for MA authors to report treatment harm comprehensively., (© 2016 European Society of Endocrinology.)

Background: Acetylcholinesterase inhibitor (AChEI) and memantine are recognized drug treatments with limited clinical efficacy. Combination therapy for patients with Alzheimer disease (AD) was suggested, but the additional benefit of combination therapy is still controversial., Aim: To evaluate the additional benefit of combination therapy over monotherapy with either AChEI or memantine., Methods: Prospective randomized controlled trials were searched from the OVID databases. The trials were eligible if study subjects were diagnosed with AD, and were randomized to compare combination therapy with monotherapy. Any clinical assessment measured using validated scales on cognitive function, activities of daily living, behavioral problems, and global changes were the primary outcomes, and any reported adverse events were the secondary outcomes. Quality of studies and risk of bias were evaluated., Results: Fourteen randomized trials were identified between 2004 and 2015 from the United States, Canada, Germany, Japan, China, and Korea. A total of 5019 patients with AD were randomly assigned to receive combination therapy of AChEI and memantine or monotherapy with AChEI or memantine. Combination therapy showed no significant benefit on cognitive function (mean difference [MD] of MMSE = 0.06, 95% CI -0.52 to 0.65), activities of daily living (MD of ADCS-ADL = -0.15, 95% CI -1.08 to 0.78), neuropsychiatric symptoms and behavioral problems (MD of NPI = -1.85, 95% CI -4.83 to 1.13), and global changes (MD of CIBIC-plus = 0.01, 95% CI -0.25 to 0.28). In subgroup analyses, combination therapy can improve cognitive function more than memantine alone; and it can significantly relieve neuropsychiatric symptoms and behavioral problems when concomitantly used with donepezil. No additional adverse event was reported in the combination therapy., Conclusion: Combination therapy only showed the benefit on neuropsychiatric symptoms and behavioral problems in moderate-to-severe AD, but no other superiority in terms of cognitive function, activities of daily living, and global changes. Although reported adverse events were comparable, the additional cost for combination therapy may be unnecessary., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Study Aim: Previous studies have shown that both scheduled second-look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis., Patients and Methods: Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %., Results: A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001)., Conclusions: After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding., Trial Registration: ClinicalTrials.gov (NCT: 00164931)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Many strategies are used to prevent nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal toxicity, but the comparative effectiveness remains unclear., Aim: To evaluate the comparative effectiveness of clinical strategies for preventing gastrointestinal toxicity induced by NSAIDs., Methods: MEDLINE, EMBASE and the Cochrane Library (from their inception to May 2015) were searched for randomised controlled trials comparing the risk of gastrointestinal adverse events in patients taking nonselective NSAIDs, selective cyclooxygenase(COX)-2 inhibitors or nonselective NSAIDs/COX-2 inhibitors plus gastroprotective agents [proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol]. Both pairwise meta-analysis and Bayesian network meta-analysis were performed., Results: Analyses were based on 82 trials including 125 053 participants. Network meta-analysis demonstrated that selective COX-2 inhibitors + PPIs [Risk ratio (RR), 95% Credible Interval (CrI): ulcer complications 0.07, 0.02-0.18], selective COX-2 inhibitors (RR, 95% CrI: ulcer complications 0.25, 0.15- 0.38; symptomatic ulcer 0.12, 0.04-0.30), nonselective NSAIDs + PPIs (RR, 95% CrI: ulcer complications 0.28, 0.18-0.41; symptomatic ulcer 0.11, 0.04-0.23), nonselective NSAIDs + misoprostol (RR, 95% CrI: ulcer complications 0.47, 0.24-0.81; symptomatic ulcer 0.41, 0.13-1.00) were associated with significantly lower risk of clinical gastrointestinal events compared with nonselective NSAIDs. For all effectiveness endpoints, selective COX-2 inhibitors + PPIs was associated with the lowest absolute event probability and the highest rank, followed by selective COX-2 inhibitors and thirdly by nonselective NSAIDs + PPIs., Conclusion: The combination of selective COX-2 inhibitors plus PPIs provides the best gastrointestinal protection, followed by selective COX-2 inhibitors, and thirdly by nonselective NSAIDs plus PPIs., (© 2016 John Wiley & Sons Ltd.)

Background: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results., Aim: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC., Methods: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT)., Results: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8-15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7-95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC., Conclusion: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel., (© 2016 John Wiley & Sons Ltd.)

Background: In patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC), high viral load was associated with tumour recurrence and deaths., Aims: To investigate the effect of nucleos(t)ide analogues (NA) on the clinical outcomes after different HCC treatments., Methods: A territory-wide cohort study was conducted using the database from Hospital Authority. We identified CHB patients with HCC by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in 2000-2012. HCC treatments, NA use and laboratory parameters were retrieved. The primary endpoint was HCC recurrence and death. A 3-month landmark analysis was used to evaluate the primary outcome in patients with or without NA treatment., Results: A total of 2198 CHB patients (1230 NA-untreated and 968 NA-treated) with HCC, receiving at least one type of HCC treatment were included in the analysis. At a median follow-up of 2.8 (IQR 1.4-4.9) years, tumour recurrence and death occurred in 451 (36.7%) and 578 (47.0%) untreated patients; and in 216 (22.3%) and 301 (31.1%) NA-treated patients respectively. NA therapy reduced the risk of overall HCC recurrence [adjusted sub-hazard ratio (SHR) 0.63, 95% confidence interval (CI) 0.49-0.80; P < 0.001]. The effect was most obvious in patients undergoing resection (SHR = 0.58, 95% CI = 0.37-0.91, P = 0.018). The possibility of NA therapy reducing the risk of death (HR = 0.82, 95% CI = 0.64-1.03, P = 0.092), is most obvious in resection subgroup (HR = 0.64, 95% CI = 0.41-0.99, P = 0.050) but insignificant in the other treatment groups., Conclusion: Our findings show that nucleos(t)ide analogues treatment reduces the risk of HCC recurrence in patients with chronic hepatitis B treated by surgical resection., (© 2016 John Wiley & Sons Ltd.)

Objective: Interferon γ release assay (IGRA) is commonly used to diagnose latent TB infection (LTBI). Immunosuppressive therapy may affect its performance but data are conflicting. We aimed to determine the effect of immunosuppressive therapy on the performance of IGRA in patients with autoimmune diseases., Methods: We searched PubMed, MEDLINE, EMBASE and the Cochrane Library up to December 2014. We included studies that reported the IGRA results in patients with autoimmune disease with or without immunosuppressive therapy. The pooled effect of immunosuppressive therapy on IGRA was estimated using a Peto fixed-effects model., Results: We included 17 studies with 3197 participants in the meta-analysis. Among the subjects, 71.5% were taking immunosuppressive therapy and 56.7% had received Bacillus Calmette-Guérin vaccination. Compared with patients not on immunosuppressants, patients receiving immunosuppressive therapy were less likely to have a positive IGRA result (OR 0.66, 95% CI 0.53 to 0.83, I(2)=23%), especially patients receiving anti-tumour necrosis factor (anti-TNF) treatment (OR 0.50, 95% CI 0.29 to 0.88). The use of immunosuppressive therapy was also associated with a lower rate of positive tuberculin skin test result (OR 0.51, 95% CI 0.42 to 0.61)., Conclusions: Our meta-analysis showed that IGRA results are negatively affected by immunosuppressive therapy. IGRA alone may not be sufficiently sensitive to diagnose LTBI in patients on immunosuppressive therapy. Patients should preferably be screened for LTBI before initiation of immunosuppressive therapy, especially before anti-TNF therapy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Alzheimer disease (AD) is a global health problem which afflicts millions of old age population worldwide. Acetylcholinesterase inhibitors and memantine are recognized drug treatments with limited clinical efficacy. It is uncertain if earlier initiation of these drugs will result in better outcomes in the longer term., Aim: To evaluate the benefit of early treatment among people with AD., Methods: Prospective randomized controlled trials were systematically searched from the OVID databases. The trials were eligible if study participants diagnosed with AD and were randomized to have early or late treatment. Any clinical assessment scales on cognitive function, physical function, behavioral problems, and the overall clinical status were the primary outcomes, and any reported adverse events were the secondary outcomes., Results: Ten randomized trials were identified between 2000 and 2010. A total of 3092 participants with AD with mean age 75.8 years were randomly assigned to receive early treatment or treatment delayed by placebo intervention for around 6 months. Compared with late treatment, early AD drug treatment showed no significant benefit on cognitive function [mean difference (MD) of Alzheimer's Disease Assessment Scale- Cognitive Subscale = -0.49, 95% CI = -1.67 to 0.69], physical function (MD of Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory = 0.47, 95% CI = -1.44 to 2.39), behavioral problems (MD of Neuropsychiatric Inventory = -0.26, 95% CI = -2.70 to 2.18), and clinical status (MD of Clinician's Interview-Based Impression of Change plus Caregiver Input = 0.02, 95% CI = -0.23 to 0.27). Nausea was the most common adverse events in acetylcholinesterase inhibitor users, while memantine did not result in more side effects than the placebo group. For both drugs, early treatment had comparable adverse events when compared with late treatment., Conclusions: Earlier AD drug treatment by around 6 months did not result in significant difference in cognitive function, physical function, behavioral problems, and clinical status. This study included relative high proportion of early AD with the follow-up less than 2 years. Future studies can be conducted to further investigate the long-term findings., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Chinese herbal medicines (CHM) are often used in managing cancer related symptoms but their effectiveness and safety is controversial. We conducted this overview of meta-analyses to summarize evidence on CHM for cancer palliative care. We included systematic reviews (SRs) with meta-analyses of CHM clinical trials on patients diagnosed with any type of cancer. Methodological quality of included meta-analyses was assessed with the Methodological Quality of Systematic Reviews (AMSTAR) Instrument. Fifty-one SRs with meta-analyses were included. They covered patients with lung (20 SRs), gastric (8 SRs), colorectal (6 SRs), liver (6 SRs), breast (2 SRs), cervical (1 SR), esophageal (1 SR), and nasopharyngeal (1 SR) cancers. Six SRs summarized evidence on various types of cancer. Methodological quality of included meta-analyses was not satisfactory. Overall, favorable therapeutic effects in improving quality of life among cancer patients have been reported. Conflicting evidence exists for the effectiveness of CHM in prolonging survival and in reducing chemotherapy and/or radiotherapy related toxicities. No serious adverse effects were reported in all included studies. Evidence indicated that CHM could be considered as an option for improving quality of life among patients receiving palliative care. It is unclear if CHM may increase survival, or reduce therapy related toxicities.

Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are often used to manage cancer-related symptoms, but their effectiveness and safety are controversial. We conducted this overview to summarise the evidence on acupuncture for palliative care of cancer. Our systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews in this overview, assessed using the Methodological Quality of Systematic Reviews Instrument, was found to be satisfactory. There is evidence for the therapeutic effects of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. There is conflicting evidence regarding the treatment of cancer-related pain, hot flashes and hiccups, and improving patients' quality of life. The available evidence is currently insufficient to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Because acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer, especially for clinical problems for which conventional care options are limited.

Unlabelled: Widespread and long-term use of oral nucleos(t)ide analogs (NAs) to treat chronic hepatitis B (CHB) brings about safety data in a real-life setting. We aimed to determine the risks of renal and bone side effects in patients receiving or who have received NAs as CHB treatment. A territory-wide cohort study using the database from Hospital Authority, the major provider of medical services in Hong Kong, was conducted. We identified CHB patients by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary events were renal (incident renal failure and renal replacement therapy [RRT]) and bone events (incident hip, vertebral, and all fractures). A 3-year landmark analysis was used to evaluate the relative risk of primary outcome in patients with or without NA treatment. A total of 53,500 CHB patients (46,454 untreated and 7,046 treated), who were event free for 3 years, were included in the analysis. At a median follow-up of 4.9 years, chronic renal failure, RRT, all fractures, hip fractures, and vertebral fractures occurred in 0.6%, 0.2%, 0.7%, 0.1%, and 0.1% of untreated subjects and 1.4%, 0.7%, 1.3%, 0.2%, and 0.2% of treated subjects. After propensity score weighting, NA therapy did not increase the risk of any of the events (hazard ratios [HRs] ranged from 0.79 to 1.31; P = 0.225-0.887). Exposure to nucleotide analogues, compared with nucleoside analogs, increased the risk of hip fracture (HR = 5.69; 95% confidence interval: 1.98-16.39; P = 0.001), but not other events (HR = 0.58-1.44; P = 0.202-0.823)., Conclusions: NA treatment does not increase the risk of renal and bone events in general. Nucleotide analogs may increase the risk of hip fracture, but the overall event rate is low., (© 2015 by the American Association for the Study of Liver Diseases.)

Importance: Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available., Objective: To evaluate the diagnostic performance of all cognitive tests for the detection of dementia., Data Sources: Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search., Study Selection: Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance., Main Outcomes and Measures: Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes., Results: Eleven screening tests were identified among 149 studies with more than 49,000 participants. Most studies used the MMSE (n = 102) and included 10,263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrooke's Cognitive Examination-Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity., Conclusions and Relevance: Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.

Background: Computer-assisted cognitive remediation (CACR) has been demonstrated to enhance cognition of patients with severe mental illness (SMI). Patients with improved cognitive skills may find it easier to be employed, and the ability to maintain employment is an important sign of recovery., Aim: To assess whether CACR is an effective method to enhance work-related outcomes in patients with SMI., Method: Prospective controlled trials evaluating CACR on productivity outcomes were systematically identified from the OVID databases. Employment rates, total days of work in a year, and total annual earnings were defined as the productivity outcomes., Results: Nine trials were published between 2005 and 2014 and were conducted in the United States, Germany, Italy, Singapore and Japan. A total of 740 patients with mean age of 36.4 years were included. The duration of CACR ranged from 2 months to 2 years, and the patients were followed-up from 1 year to 3 years. Patients receiving CACR showed 20% higher employment rate (95% CI = 5%-35%), worked 19.5 days longer in a year (95% CI = 2.5-36.6 days), and earned US$959 more in total annual earnings (95% CI = US$285 to US$1634) than those not receiving CACR., Conclusion: CACR can enhance productivity outcomes for patients with SMI, including higher employment rate, longer duration of work and higher income. The economic benefit of CACR can enhance the quality of life for patients with SMI, and may reduce financial burden on the health and welfare system. Therefore, CACR can be recommended and incorporated into regular vocational rehabilitation programs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Serrated polyps of the colon comprise a heterogeneous group of lesions with distinct histological and malignant features. The presence of serrated polyps has been associated with synchronous advanced neoplasia, although the magnitude of this relationship is unclear., Methods: Using studies identified from systematic literature search up to February 2014, we performed a systematic review and meta-analysis to estimate the pooled prevalence of serrated polyps and their association with synchronous advanced neoplasia. Random-effects models were used to combine estimates from heterogeneous studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented., Results: Nine studies with 34,084 participants were included. The mean age of subjects was 59.9±6.6 years and 52.5% of the subjects were male. Pooled prevalence of serrated polyps was 15.6% (95% CI, 10.3-22.9%). The pooled OR of advanced neoplasia in individuals with serrated polyps was 2.05 (95% CI, 1.38-3.04). Pooled analysis showed that the presence of proximal serrated polyps (OR=2.77, 95% CI, 1.71-4.46) and large serrated polyps (OR=4.10, 95% CI, 2.69-6.26) was associated with an increased risk of synchronous advanced neoplasia. The pooled OR for advanced neoplasia in individuals with proximal and large serrated polyps was 3.35 (95% CI, 2.51-4.46). Considerable heterogeneity was observed in most analyses., Conclusions: Our meta-analysis showed that serrated polyps are associated with a more than twofold increased risk of detection of synchronous advanced neoplasia. Individuals with proximal and large serrated polyps have the highest risk. These individuals deserve surveillance colonoscopy.

Background: Varicella is a highly infectious childhood disease. Tetravalent measles-mumps-rubella-varicella (MMRV) vaccine was introduced as one-syringe dose., Objective: To evaluate the immunogenicity and reactogenicity of MMRV vaccine versus trivalent MMR with varicella (V) vaccines in healthy children and to assess the respective safety issue., Methods: Randomized controlled trials (RCTs) were searched from the OVID databases. Trials were eligible if healthy children were randomized to receive MMRV or MMR+V vaccine. Seroconversions in serum antibody titers were the primary outcomes; adverse events were the secondary outcomes., Results: Ten RCTs with 8961 healthy children were identified. MMRV and MMR+V vaccines showed comparable immunogenicity against measles (relative risk [RR] = 0.99, 95% CI = 0.98-1.00), mumps (RR = 0.99, 95% CI = 0.97-1.00), rubella (RR = 1.00, 95% CI = 1.00-1.01) and varicella (RR = 0.98, 95% CI = 0.95-1.01). At least 93% of children in both groups had seroconverted within 6 weeks. MMRV group showed significantly higher incidences of fever (RR = 1.19, 95% CI = 1.09-1.31) and rash (RR = 1.23, 95% CI = 1.06-1.43)., Conclusions: The immunogenicities of MMRV and MMR+V vaccines were comparable in healthy children; however, MMRV vaccination showed higher incidences of fever and rash.

Assessment of mucosal inflammation is important in the management of patients with ulcerative colitis (UC). Colon capsule endoscopy (CCE) has recently been shown to be effective in colorectal polyp detection. However, its role in the evaluation of mucosal inflammation in UC is unclear. This systematic review aims to clarify the state of the art with an evidence-based summary of current studies on the utility of CCE in UC. The overall results show that the accuracy of CCE for assessment of mucosal inflammation in UC appeared to be comparable with that of colonoscopy. Long-term follow-up studies with larger sample size are needed to further validate the utility of CCE in the management of UC subjects in clinical practice.

Objective: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations., Design: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements., Results: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening., Conclusions: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: A meta-analysis may provide more conclusive results than a single trial. The major cost of meta-analysis is the time of waiting before the meta-analysis becomes available and resources spent on consequent trials that may not be necessary. The objective of this study is to address how often the result of a single trial, in particular the first trial, differs from that of its corresponding meta-analysis so as to reduce unnecessary waiting time and subsequent trials., Study Design and Settings: A meta-epidemiologic study was conducted by collecting meta-analyses from the Cochrane Database of Systematic Reviews and five major medical journals. Effect size of a single trial was compared with that of its corresponding meta-analysis. The single trial includes the first trial, last trial and any trial randomly selected from the meta-analysis., Results: 647 meta-analyses are included and the median number of trials in a meta-analysis is 5. 233 (36.0%) meta-analyses have the first trial with a statistically significant result. When the first trial is statistically significant, 84.1% (95% CI: 79.4%, 88.8%) of the corresponding meta-analyses is both in the same direction and statistically significant. When the first trial is statistically insignificant, 57.9% (95% CI: 53.2%, 62.8%) of the meta-analysis is also statistically insignificant regardless of direction. The median number of years is 6.5 years from the first to the 5th trial., Conclusion: The conclusion of the first trial that the treatment is effective or harmful is mostly likely correct. A statistically significant trial agrees more often with its corresponding meta-analysis than a large trial. These findings imply that particularly in some urgent, life-saving or other critical circumstances for which no other effective methods are available, cautious recommendation based on the significant result of the first trial seems justifiable and could start use of an effective intervention by 5-8 years earlier.

Background: Perindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors., Methods: All adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular-specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias., Results: A total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5% vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01-1.16) and 1.18-fold (95% C.I. 1.02-1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged >70 years. The additional models controlled for propensity scores yielded comparable results., Conclusions: The long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70 years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background and Aims: Distinguishing Crohn's disease (CD) from intestinal tuberculosis (ITB) is a clinical challenge. This meta-analysis assessed the clinical usefulness of Interferon-gamma releasing assay (IGRA) and anti-Saccharomyces cerevisiae antibody (ASCA) in the diagnosis of ITB and CD, respectively., Methods: Systematic search without language restriction was conducted in AMED, EBM, MEDLINE, EMBASE, and Google Scholar until September 2013. Studies that have evaluated performance of IGRA (QuantiFERON-TB Gold or T-SPOT.TB) or ASCA in distinguishing ITB from CD were eligible. Main outcome measures included sensitivity and specificity. Random-effects models were used to combine estimates from studies with significant heterogeneity. Area under the curve (AUC) was used to measure accuracy of the tests., Results: Eleven studies (five IGRA, three ASCA, three IGRA and ASCA) involving 1081 subjects were included. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of IGRA for the diagnosis of ITB was 81% (95% CI, 75-86%), 85% (95% CI, 81-89%), 6.02 (95% CI: 4.62-7.83), and 0.19 (95% CI: 0.10-0.36), respectively. The AUC was 0.92. The pooled sensitivity and specificity of ASCA for the diagnosis of CD was 33% (95% confidence interval [CI], 27%-38%) and 83% (95% CI, 77-88%), respectively with an AUC of 0.58. T-SPOT.TB showed a higher sensitivity than QuantiFERON-TB Gold for the diagnosis of ITB., Conclusions: IGRA and ASCA have a high specificity for the diagnosis of ITB. Both IGRA and ASCA may have a supplementary role in the differential diagnosis between ITB and CD when conventional workup is not diagnostic., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objectives: The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis., Methods: This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis., Results: A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups., Conclusions: High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.

Objective: We aim to develop and validate a clinical scoring system to predict the risks of colorectal neoplasia to better inform screening participants and facilitate their screening test choice., Design: We recruited 5220 Chinese asymptomatic screening participants who underwent colonoscopy in Hong Kong during 2008-2012. From random sampling of 2000 participants, independent risk factors were evaluated for colorectal neoplasia, defined as adenoma, advanced neoplasia, colorectal cancer or any combination thereof using binary regression analysis. The ORs for significant risk factors were used to develop a scoring system ranging from 0 to 6: 0-2 'average risk' (AR) and 3-6 'high risk' (HR). The other 3220 screening participants prospectively enrolled between 2008 and 2012 for screening colonoscopy formed an independent validation cohort. The performance of the scoring system for predicting colorectal neoplasia was evaluated., Results: The prevalence of colorectal neoplasia in the derivation and validation cohorts was 31.4% and 30.8%, respectively. Using the scoring system developed, 78.9% and 21.1% in the validation cohort were classified as AR and HR, respectively. The prevalence of colorectal neoplasia in the AR and HR groups was 27.1% and 44.6%, respectively. The subjects in the HR group had 1.65-fold (95% CI 1.49 to 1.83) increased prevalence of colorectal neoplasia than the AR group., Conclusions: The scoring system based on age, gender, smoking, family history, Body Mass Index and self-reported diabetes is useful in predicting the risk of colorectal neoplasia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects., Purpose: To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings., Methods: Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables., Results: The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, p<0.001); overweight (BMI=23-24.9, AOR=1.52, 95% CI=1.12, 2.07, p=0.007); obesity (BMI≥25, AOR=1.56, 95% CI=1.15, 2.10, p=0.004); hypertension (AOR=1.58, 95% CI=1.21, 2.06, p=0.001); and alcohol consumption (AOR=1.47, 95% CI=1.05, 2.06, p=0.025) were associated with ACN. The c-statistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001)., Conclusions: Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening., (Copyright © 2014. Published by Elsevier Inc.)

Background: Obstructive sleep apnea (OSA), caused by the obstruction of the upper airway, is the most common type of sleep apnea. Continuous positive airway pressure (CPAP) and positional therapy have been shown to be effective to improve positional OSA., Aim: To compare the effectiveness of positional therapy versus CPAP on positional OSA., Methods: Prospective randomized trials were systematically searched from the OVID databases. The trials comparing positional therapy versus CPAP in patients with positional OSA were included. Apnea-hypopnea index (AHI), mean oxygen saturation level, arousal index, sleep efficiency, and sleep time were the outcomes of this meta-analysis., Results: Three crossover trials were identified from Canada, New Zealand, and United States from 1999 to 2010. A total of 71 patients were randomly assigned to receive CPAP or positional therapy and the mean age of patients was 51 y. Positional therapy showed higher AHI (mean difference, MD: 4.28, 95% CI: 0.72-7.83) and lower oxygen saturation level (MD: -1.04, 95% CI: -1.63 to -0.46) than CPAP. It showed no distinct advantage over CPAP in terms of arousal index, sleep efficiency, and total sleep time, but CPAP reduced sleep time in the supine position., Conclusion: CPAP is superior to positional therapy in reducing the severity of sleep apnea and increasing the oxygen saturation level in patients with positional OSA., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The efficacy of adjuvant use of intravenous proton pump inhibitors (PPIs) after endoscopic therapy has been proved in peptic ulcer bleeding patients, but the efficacy of oral PPIs is uncertain., Aim: To compare the clinical outcomes of oral PPIs vs. intravenous PPIs in patients with peptic ulcer bleeding., Methods: Prospective randomised controlled trials were systematically searched from OVID databases until June 2012. Trials comparing oral and intravenous PPIs among patients with peptic ulcer bleeding were included. Recurrent bleeding, length of hospitalisation, blood transfusion, requirement of surgery and mortality were measured. The risk of bias, study quality and heterogeneity were also evaluated., Results: Six randomised trials from 2006 to 2011 were included. A total of 615 patients were randomly assigned to receive oral PPIs (n = 302) or intravenous PPIs (n = 313). The mean age was 60 years and 71.1% was male. No significant difference between oral and intravenous PPIs was observed regarding recurrent bleeding (RR: 0.92, 95% CI: 0.56-1.50), mean volume of blood transfused (-0.02 unit, 95% CI: -0.29-0.24 unit), requirement of surgery (RR: 0.82, 95% CI: 0.19-3.61) and all-cause mortality (RR: 0.88, 95% CI: 0.29-2.71). The duration of hospital stay in days was significantly shortened in those using oral PPIs (-0.74 day, 95% CI: -1.10 day to -0.39 day)., Conclusion: Oral PPIs demonstrate a similar effectiveness to intravenous PPIs among patients with peptic ulcer bleeding, but the results were combined from open-labelled trials with limited sample size. A large double-blind non-inferiority trial is required to better assess the role of oral PPIs., (© 2013 John Wiley & Sons Ltd.)

Background: Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited., Aim: To systematically review the literature on the efficacy of herbal therapy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD)., Methods: Publications in English and non-English literatures (MEDLINE, EMBASE, EBM Reviews, AMED, Global Health) were searched from 1947 to 2013 for controlled clinical studies of herbal therapy in IBD. Outcome measures included response and remission rates., Results: Twenty-one randomised controlled trials (14 UC; 7 CD) including a total of 1484 subjects (mean age 41, 50% female) were analysed. In UC, aloe vera gel, Triticum aestivum (wheat grass juice), Andrographis paniculata extract (HMPL-004) and topical Xilei-san were superior to placebo in inducing remission or response, and curcumin was superior to placebo in maintaining remission; Boswellia serrata gum resin and Plantago ovata seeds were as effective as mesalazine, whereas Oenothera biennis (evening primrose oil) had similar relapse rates as omega-3 fatty acids in the treatment of UC. In CD, Artemisia absinthium (wormwood) and Tripterygium wilfordii were superior to placebo in inducing remission, and preventing clinical recurrence of post-operative CD respectively., Conclusions: Randomised controlled trials of herbal therapy for the treatment of IBD show encouraging results but studies remain limited and heterogenous. Larger controlled studies with stricter endpoints and better-defined patient groups are required to obtain more conclusive results on the use of CAM therapies in IBD., (© 2013 John Wiley & Sons Ltd.)

Objectives: The role of cap-assisted colonoscopy (CAC) in polyp detection and cecal intubation is unclear. We conducted a meta-analysis to compare the efficacy of CAC vs. standard colonoscopy (SC)., Methods: Publications in English and non-English literatures (OVID, MEDLINE, and EMBASE) and abstracts in major international conferences were searched for controlled trials comparing CAC and SC. Outcome measures included the proportion of patients with polyps or adenomas detected, cecal intubation rate, cecal intubation time, and total colonoscopy time. The statistical heterogeneity of trials was examined and the effects were pooled by random-effects model. The risk of bias was evaluated by the assessment tool from the Cochrane Handbook. Subgroup analyses were performed for possible clinical and methodological heterogeneities., Results: From 2,358 citations, 16 randomized controlled clinical trials were included consisting of 8,991 subjects (CAC: 4,501; SC: 4,490). Mean age of subjects was 61.0 years old and 60% were males. CAC detected a higher proportion of patients with polyp(s) (relative risk (RR): 1.08; 95% confidence interval (CI): 1.00-1.17) and reduced the cecal intubation time (mean difference: -0.64 min; 95% CI: -1.19 to -0.10). Cecal intubation rate (RR: 1.00; 95% CI: 0.99-1.02) and total colonoscopy time (mean difference: -0.97 min; 95% CI: -2.33 to 0.40) were comparable between the two groups. In subgroup analyses, a short cap (≤4 mm) was associated with improved polyp detection, whereas a long cap (≥7 mm) was associated with a shorter cecal intubation time., Conclusions: CAC demonstrated marginal benefit over SC for polyp detection and shortened the cecal intubation time.

Background: Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease-predisposing genes in Asian IBD patients., Methods: A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews., Results: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians., Conclusions: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Objectives: Urgent endoscopic intervention is important in the management of patients with peptic ulcer bleeding (PUB). Hospital admission on Sundays or on public holidays may be associated with an increased mortality. This study sets to investigate whether mortality among patients with PUB differs between holiday and weekday admissions, and also to investigate the association between mortality and the waiting time for endoscopy., Methods: Patients with PUB admitted to the Prince of Wales Hospital from 1993 to 2005 were prospectively recruited in the data set. Mortality and cause of death were documented. Predicting variables included patient characteristics, waiting time for endoscopy, and holiday or weekday admissions. Bivariate analyses and multivariate logistic regression models were used to evaluate risk factors on 30-day mortality after endoscopy., Results: A total of 8,222 patients with PUB were enrolled among which 1,573 (19.1%) were admitted on holidays. A total of 334 (4.1%) patients died within 30 days after hospital admission. There was no significant difference in mortality rate between holiday and weekday admissions (4.1 vs. 4.0%, P=0.876). Using logistic regression adjusted for age, hemodynamic shock, ulcer history, and severe comorbid illness, the waiting time for endoscopy was correlated with the risk of 30-day mortality (odds ratio (OR), 95% confidence interval (95% CI)=1.10, 1.06-1.14). Holiday admission has not increased the mortality risk (OR, 95% CI=1.07, 0.80-1.43)., Conclusions: When therapeutic endoscopy can be offered within 1 day after admission for PUB, holiday admission will not adversely affect bleeding mortality.

Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.