Time series models show comparable projection performance with joinpoint regression: A comparison using historical cancer data from World Health Organization.

Background: Cancer is one of the major causes of death and the projection of cancer incidences is essential for future healthcare resources planning. Joinpoint regression and average annual percentage change (AAPC) are common approaches for cancer projection, while time series models, traditional ways of trend analysis in statistics, were considered less popular. This study aims to compare these projection methods on seven types of cancers in 31 geographical jurisdictions. Methods: Using data from 66 cancer registries in the World Health Organization, projection models by joinpoint regression, AAPC, and autoregressive integrated moving average with exogenous variables (ARIMAX) were constructed based on 20 years of cancer incidences. The rest of the data upon 20-years of record were used to validate the primary outcomes, namely, 3, 5, and 10-year projections. Weighted averages of mean-square-errors and of percentage errors on predictions were used to quantify the accuracy of the projection results. Results: Among 66 jurisdictions and seven selected cancers, ARIMAX gave the best 5 and 10-year projections for most of the scenarios. When the ten-year projection was concerned, ARIMAX resulted in a mean-square-error (or percentage error) of 2.7% (or 7.2%), compared with 3.3% (or 15.2%) by joinpoint regression and 7.8% (or 15.0%) by AAPC. All the three methods were unable to give reasonable projections for prostate cancer incidence in the US. Conclusion: ARIMAX outperformed the joinpoint regression and AAPC approaches by showing promising accuracy and robustness in projecting cancer incidence rates. In the future, developments in projection models and better applications could promise to improve our ability to understand the trend of disease development, design the intervention strategies, and build proactive public health system.

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.

Diagnostic performance of digital cognitive tests for the identification of MCI and dementia: A systematic review.

BACKGROUND: The use of digital cognitive tests is getting common nowadays. Older adults or their family members may use online tests for self-screening of dementia. However, the diagnostic performance across different digital tests is still to clarify. The objective of this study was to evaluate the diagnostic performance of digital cognitive tests for MCI and dementia in older adults. METHODS: Literature searches were systematically performed in the OVID databases. Validation studies that reported the diagnostic performance of a digital cognitive test for MCI or dementia were included. The main outcome was the diagnostic performance of the digital test for the detection of MCI or dementia. RESULTS: A total of 56 studies with 46 digital cognitive tests were included in this study. Most of the digital cognitive tests were shown to have comparable diagnostic performances with the paper-and-pencil tests. Twenty-two digital cognitive tests showed a good diagnostic performance for dementia, with a sensitivity and a specificity over 0.80, such as the Computerized Visuo-Spatial Memory test and Self-Administered Tasks Uncovering Risk of Neurodegeneration. Eleven digital cognitive tests showed a good diagnostic performance for MCI such as the Brain Health Assessment. However, all the digital tests only had a few validation studies to verify their performance. CONCLUSIONS: Digital cognitive tests showed good performances for MCI and dementia. The digital test can collect digital data that is far beyond the traditional ways of cognitive tests. Future research is suggested on these new forms of cognitive data for the early detection of MCI and dementia.

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.

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.

Global incidence of prostate cancer in developing and developed countries with changing age structures.

To investigate the global incidence of prostate cancer with special attention to the changing age structures. Data regarding the cancer incidence and population statistics were retrieved from the International Agency for Research on Cancer in World Health Organization. Eight developing and developed jurisdictions in Asia and the Western countries were selected for global comparison. Time series were constructed based on the cancer incidence rates from 1988 to 2007. The incidence rate of the population aged ≥ 65 was adjusted by the increasing proportion of elderly population, and was defined as the "aging-adjusted incidence rate". Cancer incidence and population were then projected to 2030. The aging-adjusted incidence rates of prostate cancer in Asia (Hong Kong, Japan and China) and the developing Western countries (Costa Rica and Croatia) had increased progressively with time. In the developed Western countries (the United States, the United Kingdom and Sweden), we observed initial increases in the aging-adjusted incidence rates of prostate cancer, which then gradually plateaued and even decreased with time. Projections showed that the aging-adjusted incidence rates of prostate cancer in Asia and the developing Western countries were expected to increase in much larger extents than the developed Western countries.

Global Increasing Incidence of Young-Onset Colorectal Cancer Across 5 Continents: A Joinpoint Regression Analysis of 1,922,167 Cases.

BACKGROUND: Colorectal cancer incidence among young adults in the United States is on the rise, but whether this phenomenon is present in other parts of the world is not well documented. This study aims to explore the temporal change of incidence rates for colorectal cancer in various countries across the globe. METHODS: We extracted colorectal cancer incidence and population data from 1988 to 2007 based on data from the International Agency for Research on Cancer and compared incidence between age groups. Twelve representative jurisdictions from five continents were selected. Young-onset colorectal cancer cases were defined as those ages <50 years. Joinpoint regression was used to measure the trends of colorectal cancer incidence and to estimate the annual percent change (APC). RESULTS: The APC for those ages <50 years was noted to be increasing at a faster rate as compared with those ages ≥50 years in many regions, including Australia (+1.10% vs. -0.35%), Brazil (+9.20% vs. +5.72%), Canada (+2.60% vs. -0.91%), China-Hong Kong (+1.82% vs. -0.10%), China-Shanghai (+1.13% vs. -2.68%), Japan (+2.63% vs. +0.90%), the United Kingdom (+3.33% vs. +0.77%), and the United States (+1.98% vs. -2.88%). These trends were largely driven by rectal cancer, except in Brazil and the United Kingdom. CONCLUSIONS: Increasing incidence of young-onset colorectal cancer was noted in many regions across the globe. IMPACT: Further studies focusing on young-onset colorectal cancer, particularly with regard to risk factors and establishing the optimal age of screening, are warranted.

A population-based age-period-cohort study of colorectal cancer incidence comparing Asia against the West.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide but incidence varied widely. Despite the role of genetics, CRC is also sensitive to macro-environmental factors. Few studies have ever compared across different countries/regions to suggest possible macro-environmental risk factors of CRC. We estimated the effects of age, period and cohort on the changes of incidence of colorectal cancer across different countries/regions. METHODS: Poisson regression age-period-cohort (APC) models were conducted to estimate the age, period and cohorts effects on CRC incidence across the West (i.e., the UK, the US and Australia) and Asia (i.e. Japan, Hong Kong, Shanghai, Singapore and India). We maximized the length of the study period according to each country's data availability. RESULTS: Western populations show upward inflections for their 1950s-1960s cohorts, while Asian populations (except India) show downward inflections for their 1950s cohorts. Japanese population also shows upward inflections for its 1960s cohorts, similar to the Western populations. There are apparent upward inflections towards the more recent cohorts for Hong Kong, Shanghai and Singapore; nevertheless, the confidence intervals are wider towards the more recent cohorts. CONCLUSION: Our findings imply an increasing risk of CRC in both Western and Asian populations as their younger cohorts reach older ages. These findings are consistent with the life course argument that macro-environmental changes associated with socio-economic development have specific effects that extend over the life course. Actions that pertain to altering lifestyle-related exposures over the life course are of great importance in combating young CRC risks in the future.

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.

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.

A modified colorectal screening score for prediction of advanced neoplasia: A prospective study of 5744 subjects.

BACKGROUND AND AIM: We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia. METHODS: Among 5744 Chinese asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort. The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into "average risk" (AR): 0; "moderate risk" (MR): 1-2; and "high risk" (HR): 3-6. The other 1915 subjects formed a validation cohort, and the performance of the score was assessed. RESULTS: The prevalence of advanced neoplasia in the derivation and validation cohorts was 5.4% and 6.0%, respectively (P = 0.395). Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis. A BMI cut-off at > 23 kg/m2 had better predictive capability and lower number needed to screen than that of > 25 kg/m2 . Utilizing the score developed, 8.4%, 57.4%, and 34.2% in the validation cohort were categorized as AR, MR, and HR, respectively. The corresponding prevalence of advanced neoplasia was 3.8%, 4.3%, and 9.3%. Subjects in the HR group had 2.48-fold increased prevalence of advanced neoplasia than the AR group. The c-statistics of the modified score had better discriminatory capability than that using predictors of APCS alone (c-statistics = 0.65 vs 0.60). CONCLUSIONS: Incorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources.

Predicted Increases in Incidence of Colorectal Cancer in Developed and Developing Regions, in Association With Ageing Populations.

BACKGROUND & AIMS: Population growth and changes in demographic structure are linked to trends in colorectal cancer (CRC) incidence. The aim of this study is to estimate future CRC incidence in the ageing population, and compare trends across developing and developed regions. METHODS: Cancer and population data were extracted from the International Agency for Research on Cancer. Annual incidence rates for the major types of cancer in 118 selected populations were extracted from 102 cancer registries in 39 countries worldwide. We selected 8 jurisdictions (from the United States, Europe, and Asia) that reported 20-year cancer incidence rates since 1988. Time series models were constructed to project cancer incidence, by sex and age, to 2030. Incidence rates for persons older than 65 years were combined and further adjusted for change of ageing population. We compared age-adjusted incidence rates among the jurisdictions. RESULTS: The total population older than 65 years old was 12,917,794 in 1988, and the number increased by almost 40% to 17,950,115 in 2007. In developed countries in the West CRC incidence is predicted to decrease by 16.3% in the United States, increase by 4.8% in the United Kingdom, and increase by 4.7% in Sweden by 2030. In developing countries, such as China (Shanghai), Croatia, and Costa Rica, CRC incidence is predicted to increase in a steep curve by 2030 because of the growing population and ageing effect; in 2030, the incidence increases were 60.5% for China, 47.0% for Croatia, and 18.5% for Costa Rica. We also predict CRC incidence will increase greatly by 2030 in Japan and Hong Kong, which are developed regions. CONCLUSIONS: With the exception of the United States, the incidence of CRC is expected to continue to rise in most regions in the coming decades, due to population growth and changes in demographic structure. The predicted increases are more marked in developing regions with limited health care resources.

Cancer burden with ageing population in urban regions in China: projection on cancer registry data from World Health Organization.

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.

Combination Therapy Showed Limited Superiority Over Monotherapy for Alzheimer Disease: A Meta-analysis of 14 Randomized Trials.

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.

Effect of immunosuppressive therapy on interferon γ release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis.

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.

Effectiveness of Chinese herbal medicine for cancer palliative care: overview of systematic reviews with meta-analyses.

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.

Effectiveness of acupuncture and related therapies for palliative care of cancer: overview of systematic reviews.

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.

Cognitive Tests to Detect Dementia: A Systematic Review and Meta-analysis.

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.