Maternal Vitamin D Status Related to Triacylglycerol in Early Pregnancy and Subsequent Risk for Adverse Pregnancy Outcomes

Research has suggested roles of vitamin D in health beyond its action on calcium homeostasis and bone health. Recent studies revealed a high proportion of pregnant women having low vitamin D status. This may lead to increased risks for preeclampsia, gestational diabetes (GDM), and cesarean delivery. Findings on the effects of vitamin D on these adverse pregnancy outcomes have been inconsistent. To our knowledge, no studies have examined maternal vitamin D status with circulating triacylglycerol (TAG) concentrations. This study was conducted to assess the effects of maternal vitamin D status on subsequent risk for pregnancy complications and to determine the effectiveness of 25-hydroxyvitamin D [25(OH)D] to TAG ratio to indicate vitamin D status. We measured the plasma 25(OH)D and TAG concentrations of 299 pregnant women in their 8th to 20th week of gestation, and examined the association between 25(OH)D concentrations, 25(OH)D/TAG ratios and the risk of preeclampsia, GDM, and cesarean delivery. Of the 299 subjects, five developed preeclampsia, 15 developed GDM, and 89 delivered their infants by cesarean section. Women diagnosed with preeclampsia or GDM had significantly lower 25(OH)D/TAG ratios than women without these complications. Women with 25(OH)D concentrations and 25(OH)D/TAG below medians had increased odds of preeclampsia (OR, 4.05; 95% CI, 0.45-36.71 and OR, 4.05; 95% CI, 0.45-36.71 respectively) and GDM (OR, 2.12; 95% CI, 0.71-6.38 and OR, 2.96, 95% CI, 0.92-9.55 respectively). These results were not statistically significant because of the small number of affected women, but the association between 25(OH)D/TAG and GDM risk was close to significant (P = 0.07). Women with 25(OH)D concentrations and 25(OH)D/TAG below medians also had reduced odds for cesarean delivery (OR, 0.54; 95% CI, 0.32-0.89 and OR, 0.74; 95% CI, 0.45-1.22 respectively), but only the association between 25(OH)D concentration and risk of cesarean delivery was statistically significant. This study suggested increased preeclampsia and GDM risks in women with low vitamin D status. Few cases of these events compromised the statistical significance of results. The increased risk of cesarean delivery in women with higher vitamin D status shown has to be reevaluated because reasons for cesarean delivery were not included in the analysis

Predator Extinction arose from Chaos of the Prey: the Chaotic Behavior of a Homomorphic Two-Dimensional Logistic Map in the Form of Lotka-Volterra Equations

A two-dimensional homomorphic logistic map that preserves features of the Lotka-Volterra equations was proposed. To examine chaos, iteration plots of the population, Lyapunov exponents calculated from Jacobian eigenvalues of the $2$D logistic mapping, and from time series algorithms of Rosenstein and Eckmann et al. were calculated. Bifurcation diagrams may be divided into four categories depending on topological shapes. Our model not only recovered the $1$D logistic map, which exhibits flip bifurcation, for the prey when there is a nonzero initial predator population, but it can also simulate normal competition between two species with equal initial populations. Despite the possibility for two species to go into chaos simultaneously, where the Neimark-Sacker bifurcation was observed, it is also possible that with the same interspecies parameters as normal but with a predator population $10$ times more than that of the prey, the latter becomes chaotic, while the former dramatically reduces to zero with only a few iterations, indicating total annihilation of the predator species. Interpreting humans as predators and natural resources as preys in the ecological system, the above-mentioned conclusion may imply that not only excessive consumption of natural resources, but its chaotic state triggered by an overpopulation of humans may backfire in a manner of total extinction of the human species. Fortunately, there is little chance for the survival of the human race, as isolated fixed points in the bifurcation diagram of the predator reveal. Finally, two possible applications of the phenomenon of chaotic extinction are proposed: one is to inhibit viruses or pests by initiating the chaotic states of the prey on which the viruses or pests rely for existence, and the other is to achieve the superconducting state with the chaotic state of the applied magnetic field.Comment: Paper abstract presented at the 33rd Annual Conference of the Society for Chaos Theory in Psychology & Life Sciences, The Fields Institute, U of Toronto, Aug. 4, 202

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

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

Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series.

BACKGROUND: Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator. METHODS: We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates. RESULTS: A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively. CONCLUSIONS: We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding

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

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

Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study

OBJECTIVE: To assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease. DESIGN: Cohort study with propensity score matching of new-users of aspirin to non-users. SETTING: Clinical Data Analysis and Reporting System database, Hong Kong. PARTICIPANTS: Adults ≥40 years with a prescription start date of either low-dose aspirin (75-300 mg/daily) or paracetamol (non-aspirin users) between 1 January 2004 to 31 December 2008 without a history of atherosclerotic cardiovascular disease. MAIN OUTCOME MEASURES: The primary outcome was the first diagnosis of gastrointestinal cancer (either CRC, GC or EC) and the secondary outcome was GIB. Individuals were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any type of cancer besides the outcome, death or until 31 December 2017. A competing risk survival analysis was used to estimate HRs and 95% CIs with death as the competing risk. RESULTS: After matching, 49 679 aspirin and non-aspirin users were included. The median (IQR) follow-up was 10.0 (6.4) years. HRs for low-dose aspirin compared with non-aspirin users were 0.83 for CRC (95% CI, 0.76 to 0.91), 0.77 for GC (95% CI, 0.65 to 0.92) and 0.88 for EC (95% CI, 0.67 to 1.16). Patients prescribed low-dose aspirin had an increased risk of GIB (HR 1.15, 95% CI, 1.11 to 1.20), except for patients prescribed proton pump inhibitors or histamine H2-receptor antagonists (HR 1.03, 95% CI, 0.96 to 1.10). CONCLUSION: In this cohort study of Chinese adults, patients prescribed low-dose aspirin had reduced risks of CRC and GC and an increased risk of GIB. Among the subgroup of patients prescribed gastroprotective agents at baseline, however, the association with GIB was attenuated

Effectiveness of BNT162b2 and CoronaVac vaccinations against SARS-CoV-2 omicron infection in people aged 60 years or above: a case–control study

BACKGROUND: In view of limited evidence that specifically addresses vaccine effectiveness (VE) in the older population, this study aims to evaluate the real-world effectiveness of BNT162b2 and CoronaVac in older adults during the Omicron BA.2 outbreak. METHODS: This case-control study analyzed data available between January and March 2022 from the electronic health databases in Hong Kong and enrolled individuals aged 60 or above. Each case was matched with up to 10 controls by age, sex, index date and Charlson Comorbidity Index for the four outcomes (COVID-19 infection, COVID-19-related hospitalization, severe complications, and all-cause mortality) independently. Conditional logistic regression was conducted to evaluate VE of BNT162b2 and CoronaVac against COVID-19-related outcomes within 28 days after COVID-19 infection among participants stratified by age groups (60-79, ≥80 years old). RESULTS: A dose-response relationship between the number of vaccine doses received and protection against severe or fatal disease was observed. Highest VE (95% CI) against COVID-19 infection was observed in individuals aged ≥80 who received three doses of BNT162b2 [75.5% (73.1-77.7%)] or three doses of CoronaVac [53.9% (51.0-56.5%)] compared to those in the younger age group who received three doses of BNT162b2 [51.1% (49.9-52.4%)] or three doses of CoronaVac [2.0% (-0.1-4.1%)]. VE (95% CI) was higher for other outcomes, reaching 91.9% (89.4-93.8%) and 86.7% (84.3-88.8%) against COVID-19-related hospitalization; 85.8% (61.2-94.8%) and 89.8% (72.4-96.3%) against COVID-19-related severe complications; and 96.4% (92.9-98.2%) and 95.0% (92.1-96.8%) against COVID-19-related mortality after three doses of BNT162b2 and CoronaVac in older vaccine recipients, respectively. A similar dose-response relationship was established in younger vaccine recipients and after stratification by sex and Charlson Comorbidity Index. CONCLUSION: Both BNT162b2 and CoronaVac vaccination were effective in protecting older adults against COVID-19 infection and COVID-19-related severe outcomes amidst the Omicron BA.2 pandemic, and VE increased further with the third dose

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes