Intake of processed meat, but not sodium, is associated with risk of colorectal cancer: Evidence from a large prospective cohort and two-sample Mendelian randomization.

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.

Use of metformin and aspirin is associated with delayed cancer incidence.

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.

Monotherapy Is Good Enough for Patients with Mild-to-Moderate Alzheimer's Disease: A Network Meta-analysis of 76 Randomized Controlled Trials.

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.

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

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

Immunogenicity and reactogenicity of tetravalent vaccine for measles, mumps, rubella and varicella (MMRV) in healthy children: a meta-analysis of randomized controlled trials.

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.

Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk Chinese: a prospective study.

OBJECTIVES: Although colonoscopy is considered the most accurate screening tool for colorectal neoplasm, the optimal interval of repeating a screening colonoscopy, particularly in average-risk subjects after a negative colonoscopy, is poorly defined. We determine the 5-year risk of advanced neoplasia on rescreening colonoscopy in a cohort of average-risk Chinese subjects. METHODS: We invited a cohort of asymptomatic average-risk Chinese subjects (aged 55-75 years) who were recruited in our previous screening colonoscopy studies to undergo a repeat colonoscopy at the end of 5 years. The rates of advanced colorectal neoplasia at the end of 5 years in these subjects were determined according to their baseline colonoscopy findings. RESULTS: A total of 511 of the 620 eligible subjects underwent repeat-screening colonoscopy at the end of 5 years. Among them, 401 subjects had no baseline neoplasia (370 with no baseline polyps and 31 with hyperplastic polyps). In subjects with no baseline polyp, 24.6% were found to have at least one adenoma and 1.4% had advanced neoplasia on rescreening. The number needed to rescreen for one advanced neoplasia in subjects with no baseline polyp was 74 (95% confidence interval (CI), 32-168). The prevalence of advanced neoplasia at 5 years in subjects with baseline-advanced neoplasia was 20.7% (relative risk 19.6; 95% CI, 5.2-74.1; vs. subjects with no baseline polyp). The presence of baseline-advanced neoplasia (odds ratio (OR) 13.1; 95% CI, 4.1-41.7) and age in years (OR 1.11; 95% CI, 1.01-1.22) are two independent factors for development of advanced neoplasia at 5 years. CONCLUSIONS: The risk of advanced neoplasia is sufficiently low 5 years after a normal screening colonoscopy in Chinese subjects.