Association Between Statin Use and the Incidence of Clinically Diagnosed Osteoarthritis: A Nationwide Retrospective Cohort Study in Taiwan.

OBJECTIVE: To investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA). DESIGN: In this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA. RESULTS: Compared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA. CONCLUSIONS: Higher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention.

Multidimensional opioid abuse deterrence using a nanoparticle-polymer hybrid formulation.

Misuse of prescription opioid drugs is the leading cause of the opioid crisis and overdose-related death. Abuse deterrent formulations (ADFs) have been developed to discourage attempts to tamper with the formulation and alter the ingestion methods. However, abusers develop complex extraction strategies to circumvent the ADF technologies. For comprehensive deterrence of drug abuse, we develop tannic acid nanoparticles (NPs) that protect encapsulated opioids from solvent extraction and thermal challenge (crisping), complementing the existing formulation strategy to deter injection abuse. Here, we develop a hybrid ADF tablet (NP-Tab), consisting of iron-crosslinked tannic acid NPs encapsulating thebaine (model opioid compound), xanthan gum, and chitosan (gel-forming polymers), and evaluate its performance in common abuse conditions. NP-Tab tampered by crushing and suspended in aqueous solvents forms an instantaneous gel, which is difficult to pull or push through a 21-gauge needle. NPs insulate the drug from organic solvents, deterring solvent extraction. NPs also promote thermal destruction of the drug to make crisping less rewarding. However, NP-Tab releases thebaine in the simulated gastric fluid without delay, suggesting that its analgesic effect may be unaffected if consumed orally as prescribed. These results demonstrate that NP-Tab can provide comprehensive drug abuse deterrence, resisting aqueous/organic solvent extraction, injection, and crisping, while retaining its therapeutic effect upon regular usage.

Association between antihyperlipidemic agents and the risk of chronic periodontitis in patients with hyperlipidemia: A population-based retrospective cohort study in Taiwan.

BACKGROUND: The lipid-lowering and anti-inflammatory effects of statins and fibrates may ameliorate periodontitis. Patients with hyperlipidemia tend to have a worse periodontal status. This study assessed the association between the use of statins/fibrates and the incidence of chronic periodontitis in patients with hyperlipidemia in Taiwan. METHODS: This retrospective cohort study enrolled patients newly diagnosed with hyperlipidemia between 2001 and 2012 from the 2000 Longitudinal Generation Tracking Database and followed them for 5 years. The study population was divided into four groups: statin monotherapy, fibrate monotherapy, combination therapy (both statins and fibrates), and control (neither statins nor fibrates). Each patient in the treatment group was matched at a ratio of 1:1 with a control. Chronic periodontitis risk was compared in the three study arms by using a Cox proportional hazard model. RESULTS: Chronic periodontitis risk was reduced by 25.7% in the combination therapy group compared with the control group (adjusted hazard ratio [aHR], 0.743; 95% confidence interval (CI), 0.678-0.815). Low dose (<360 cumulative defined daily dose [cDDD]) and shorter duration (<2 years) of statin monotherapy seem to be associated with an increased risk of chronic periodontitis; high dose (≥720 cDDD/≥1080 cDDD) and longer duration (≥3 years) of statin/fibrate monotherapy may be correlated with a lower risk of periodontitis. Hydrophobic statin users had a lower chronic periodontitis risk than hydrophilic statin users. CONCLUSION: Chronic periodontitis risk was lower in patients with hyperlipidemia on combination treatment with statins and fibrates, and the risk decreased when patients used statins or fibrates for >3 years.

Seasonal activity of spotted lanternfly (Hemiptera: Fulgoridae), in Southeast Pennsylvania.

The spotted lanternfly, Lycorma delicatula (White, 1845), is an invasive species in the United States. This pest causes damage to vineyards and has the potential to negatively affect other crops and industries. Information describing the seasonal timing of life stages can improve its management. In 2019 and 2020, spotted lanternfly seasonal activity was followed weekly from spring egg hatch to the first hard freeze. Weighted mean timing of activity for each nymphal instar, early adults, late adults, total adults, and egg mass deposition are presented for 2019 and 2020 on Acer rubrum and 2020 on Ailanthus altissima. Logistic equations describing the percentage completion of each activity period on these hosts were fitted using a start date of 1 January to calculate accumulated degree days (ADD). For the adult and egg mass deposition periods, we additionally used a biofix of the date adults were first observed to calculate ADD. ADD from 1 January adequately estimated the timing of nymphal instars but ADD from observation of the first adult better estimated the timing of adult activity and egg mass deposition. Late adult activity and egg mass deposition periods appeared to be influenced by another environmental cue, such as day length. Maps of season-long ADD show that spotted lanternflies are unlikely to reach adulthood in colder regions of the northeast United States, and therefore may not establish there. We also report a strong seasonal trend in sex ratio on A. rubrum, where the population shifted from over 80% male to over 80% female in October.

Association between Antihyperlipidemic Agent Use and Age-Related Macular Degeneration in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study.

Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving antihyperlipidemic agents. The comparison group included patients without hyperlipidemia who were randomly selected and matched with study group II patients. A Cox proportional hazard model was used to evaluate the risk of AMD among the groups. Patients with hyperlipidemia receiving antihyperlipidemic agents (study group I, n = 15,482) had a significantly increased AMD risk (adjusted hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.04-1.45) compared to those not receiving antihyperlipidemic agents (study group II, n = 15,482). However, with an increase in cumulative exposure, a reduced risk of AMD was observed in patients using a defined daily dose of more than 721, with an adjusted HR of 0.34 (95% CI = 0.22-0.53, p < 0.001). Additionally, the adjusted HR of AMD for study group II was 1.40 (95% CI = 1.20-1.63, p < 0.001) relative to the comparison group (n = 61,928). In conclusion, the study results indicated that patients with hyperlipidemia have a higher AMD risk than patients without hyperlipidemia. Furthermore, patients with hyperlipidemia who received antihyperlipidemic agents had a significantly increased AMD risk. However, a dose-dependent reduction in the risk of AMD was observed in patients with hyperlipidemia using statins or/and fibrates.

Approach to surveying egg masses of the invasive spotted lanternfly (Hemiptera: Fulgoridae).

For the invasive planthopper Lycorma delicatula, eggs are an attractive target for surveys and management because they can persist from September through May before hatching, and remnants may be retained for years after hatching. Efforts to control this invasive species, though, are hampered by imperfect detection, which impedes early detection and rapid response, obscures management impacts, and reduces the fraction of egg masses that can be managed. To estimate egg mass detectability, we conducted 75 duplicate surveys of 20 × 5 m plots located in forest edges and disturbed areas frequently used by L. delicatula. We fit binomial mixture models and investigated the effects of weather, height (above or below 3 m), season (winter or spring), and basal area of trees within plots, finding no evidence that these factors affected detection rate, which averaged 52.2%. We additionally estimated the fraction of L. delicatula eggs that were laid above 3 m, putting them outside of easy reach for management by scraping or targeted ovicide application. This proportion varied with basal area of trees within plots, and the estimated mean was greater than 50% across the range of basal areas in study plots. Finally, we found that counts of old egg masses correlated with counts of new egg masses laid the year prior, but the ability to infer prior years' egg mass counts was limited. Together, these findings inform managers delimiting L. delicatula populations in mixed habitats and those treating egg masses to slow population growth and spread of this pest.

Efficacy and nontarget effects of broadcast treatments to manage spotted lanternfly (Hemiptera: Fulgoridae) nymphs.

Management to control the spotted lanternfly, Lycorma delicatula (White), would ideally achieve managers' goals while limiting impacts on nontarget organisms. In a large-scale field study with 45 plots at least 711 m2, we tested foliar applications of dinotefuran and 2 formulations of Beauveria bassiana (Balsamo) Vuillemin, each applied from the ground and separately by helicopter. Applications targeted early instar nymphs. For both application methods, a single treatment with dinotefuran significantly reduced L. delicatula numbers, as measured by catch on sticky bands (91% reduction by air and 84% reduction by ground 19 days after application) and by timed counts (89% reduction by air and 72% reduction by ground 17 days after application). None of the B. bassiana treatments significantly reduced L. delicatula numbers, even after 3 applications. Beauveria bassiana infection in field-collected nymphs ranged from 0.4% to 39.7%, with higher mortality and infection among nymphs collected from ground application plots. Beauveria bassiana conidia did not persist for long on foliage which probably contributed to low population reduction. Nontarget effects were not observed among arthropods captured in blue vane flight intercept traps, San Jose Scale pheromone sticky traps or pitfall traps, but power analysis revealed that small reductions of less than 40% may not be detected despite extensive sampling of 48,804 specimens. These results demonstrate that dinotefuran can markedly reduce local abundance of L. delicatula with little apparent effect on nontarget insects when applied shortly after hatch, and that aerial applications can match or exceed the effectiveness of applications from the ground.

Rapid identification of carbapenem-resistant Klebsiella pneumoniae based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry and an artificial neural network model.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens. METHODS: A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously. RESULTS: Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision-recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da. CONCLUSIONS: Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients' outcomes and lower the prevalence of antimicrobial resistance.

Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study.

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia. Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models. Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90-1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84-1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47-0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34-0.67 compared with OLLA use) or a therapy duration of >3 years (aHR, 0.76; 95% CI, 0.64-0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37-0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses. Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.

Pest management in future climates: Warming reduces physical weed management effectiveness.

Climate change alters many aspects of weed performance and may also alter the effectiveness of management practices to control pests. Despite this concern, entire categories of widely used management practices, such as physical control, remain understudied in this context. We conducted a field experiment growing the invasive pest musk thistle (Carduus nutans) at ambient and experimentally elevated temperatures. We tested mowing management strategies that varied in the timing of a single mowing event relative to thistles' stem elongation phenology and compared these with an unmowed control. Results from this experiment informed demographic models to project population growth rates for different warming/mowing scenarios. Compared to plants grown under ambient conditions, warmed thistles were more likely to survive the same mowing treatment, flowered earlier in the season, grew to taller heights, and produced more flowering capitula. Proportional reductions in plant height and capitulum production caused by mowing were smaller under warming. Warming did not change the relative ranking of mowing treatments; mowing late in the growing season (2 weeks after individuals first reached a height of 40 cm) was most effective at ambient temperatures and under warming. Warming caused significant increases in projected local population growth rate for all mowing treatments. For invasive musk thistle, warmed individuals outperformed individuals grown at ambient temperatures across all the mowing treatments we considered. Our results suggest that to achieve outcomes comparable to those attainable at today's temperatures, farmers will need to apply supplemental management, possibly including additional mowing effort or alternative practices such as chemical control. We recommend that scientists test management practices under experimental warming, where possible, and that managers monitor ongoing management to identify changes in effectiveness. Information about changes in managed weeds' mortality, fecundity, and phenology can then be used to make informed decisions in future climates.

Association between GnRH analogue use and atopic diseases in patients with prostate cancer: A population-based retrospective cohort study.

PURPOSE: Gonadotropin-releasing hormone (GnRH) analogues reduce testosterone levels to castration levels in patients with prostate cancer. However, the role of testosterone in atopic diseases has remained undefined. We aimed to investigate this role. MATERIALS AND METHODS: This retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD). Patients with prostate cancer were categorized into two groups according to whether they received GnRH analogue treatment (study group I) or not (study group II), and men without prostate cancer and with no GnRH analogue use were defined to comprise the comparison group after their ages and index years were matched with group II. Cox proportional hazard models were used to assess the hazard ratio (HR) of atopic diseases. RESULTS: Group I, group II, and the comparison group comprised 663, 2,172, and 8,688 individuals, respectively. Group I had a significantly lower risk of atopic diseases (adjusted HR: 0.66, 95% CI, 0.49-0.89, p < 0.01) than did group II. A reduced risk of atopic diseases was found when GnRH analogues were prescribed for 2 months (adjusted HR 0.53, 95% CI, 0.29-0.97, p = 0.04) and 2-14 months (adjusted HR 0.66, 95% CI, 0.49-0.89, p = 0.007). No significant difference in the risk of atopic diseases between group II and the comparison group was observed. CONCLUSIONS: A decreased risk of atopic diseases was observed in patients with prostate cancer treated with GnRH analogues. Further studies are warranted to verify the association between testosterone levels and atopic diseases.

Insect Visitors of Black Cherry (Prunus serotina) (Rosales: Rosaceae) and Factors Affecting Viable Seed Production.

Since 2000, wild black cherry (Prunus serotina Ehrh.) has produced erratic seed crops, especially in the Allegheny National Forest where poor seed production has been implicated in difficulties with black cherry regeneration in forest stands. Given that black cherry is insect pollinated and unable to produce viable seed from self-pollination, a reduction in seed crops could be due to a pollination deficit; however, its key pollinators are unknown. Identifying the pollinators and factors that influence pollinator abundance and fidelity is critical for supporting and enhancing seed production for this valuable timber species. Over a two-year period in developed, semideveloped, and forested areas in Pennsylvania, we identified the potential pollinators of black cherry and examined how their abundance, along with several other abiotic and biotic factors, influenced viable seed production. We found that andrenid (Andrenidae: Hymenoptera) bees are likely the most important pollinators. The proportion of viable seeds increased as the number of andrenids increased, and these ground nesting bees were most abundant on forest edges, highlighting this habitat's potential to support pollination services. Andrenids carried an average of 347-fold more black cherry pollen than flies and 18-fold more than halictid (Halictidae: Hymenoptera) bees. We did not find a significant relationship between the abundance of any other taxa besides andrenids and viable seed production. Black cherry flowers also provide resources for natural enemies such as the economically important parasitoid of Popillia japonica Newman (Scarabaeidae: Coleoptera), Tiphia vernalis Rohwer (Tiphiidae: Hymenoptera), which was observed feeding on black cherry nectar in this study.

Weighing the unknowns: Value of Information for biological and operational uncertainty in invasion management.

The management of biological invasions is a worldwide conservation priority. Unfortunately, decision-making on optimal invasion management can be impeded by lack of information about the biological processes that determine invader success (i.e. biological uncertainty) or by uncertainty about the effectiveness of candidate interventions (i.e. operational uncertainty). Concurrent assessment of both sources of uncertainty within the same framework can help to optimize control decisions.Here, we present a Value of Information (VoI) framework to simultaneously analyse the effects of biological and operational uncertainties on management outcomes. We demonstrate this approach with a case study: minimizing the long-term population growth of musk thistle Carduus nutans, a widespread invasive plant, using several insects as biological control agents, including Trichosirocalus horridus, Rhinocyllus conicus and Urophora solstitialis.The ranking of biocontrol agents was sensitive to differences in the target weed's demography and also to differences in the effectiveness of the different biocontrol agents. This finding suggests that accounting for both biological and operational uncertainties is valuable when making management recommendations for invasion control. Furthermore, our VoI analyses show that reduction of all uncertainties across all combinations of demographic model and biocontrol effectiveness explored in the current study would lead, on average, to a 15.6% reduction in musk thistle population growth rate. The specific growth reduction that would be observed in any instance would depend on how the uncertainties actually resolve. Resolving biological uncertainty (across demographic model combinations) or operational uncertainty (across biocontrol effectiveness combinations) alone would reduce expected population growth rate by 8.5% and 10.5% respectively.Synthesis and applications. Our study demonstrates that intervention rank is determined both by biological processes in the targeted invasive populations and by intervention effectiveness. Ignoring either biological uncertainty or operational uncertainty may result in a suboptimal recommendation. Therefore, it is important to simultaneously acknowledge both sources of uncertainty during the decision-making process in invasion management. The framework presented here can accommodate diverse data sources and modelling approaches, and has wide applicability to guide invasive species management and conservation efforts.

Performance and host association of spotted lanternfly (Lycorma delicatula) among common woody ornamentals.

Lycorma delicatula (spotted lanternfly) has a broad host range with a strong preference for the invasive host plant from its native range, tree of heaven (Ailanthus altissima); it had long been speculated that L. delicatula could not develop or reproduce without access to tree of heaven. In 2019, we found that this assumption was incorrect, but fitness was reduced in the absence of A. altissima in that the number of egg masses laid was dramatically fewer for insects reared on suitable non-A. altissima host plants that had recently been established. We hypothesized that longer established, larger trees (of the same species) would improve the fitness of L. delicatula in the absence of tree of heaven. In spring 2020, we examined insect performance with and without access to A. altissima by tracking development, survival, host tree association and oviposition in large enclosures with trees planted two years prior to the study. Each enclosure included one each of Juglans nigra, Salix babylonica and Acer saccharinum along with either one A. altissima or one Betula nigra; these trees had twice the diameter of the same trees the previous year. We reared nymphs with and without access to A. altissima, released them into the corresponding large enclosures as third instars, and monitored them from early July 2020 through November 2020. We also determined whether lack of access to A. altissima by parents of L. delicatula have any fitness effects on offspring performance. To ensure adequate adult populations for comparing fecundity between treatments, third instars were released into the multi-tree enclosures due to high mortality in earlier instars that occurred in a similar study in 2019. Insect survival was higher and development faster with access to A. altissima. Third and fourth instar nymphs were most frequently observed on A. altissima when it was present, while adults were equally associated with A. saccharinum and A. altissima. In the absence of A. altissima, nymphs were most frequently found on S. babylonica, while adults were most often on A. saccharinum. Females with access to A. altissima deposited nearly 7-fold more egg masses than those without access to A. altissima, which is consistent with the difference in egg mass numbers between the two treatments the previous year; thus, our hypothesis was rejected. The offspring of parents that had been reared without access to A. altissima showed similar survival and development time from egg to adult as offspring from parents that never had access to A. altissima. These findings suggest that managers need to be aware that even in the absence of A. altissima in the landscape, several hardwood host trees can be utilized by L. delicatula to develop and reproduce, but fitness without A. altissima is likely to still be reduced.

Use of gastric acid-suppressive agents increases the risk of dementia in patients with upper gastrointestinal disease: A population-based retrospective cohort study.

BACKGROUND: Prescriptions for gastric acid-suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). METHODS: We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan's Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid-suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid-suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. RESULTS: The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid-suppressive agents compared with patients with UGID without gastric acid-suppressive agents was 1.470 (95% confidence interval [CI] 1.267-1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377-2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098-1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022-2.075], p < 0.05). CONCLUSIONS: Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid-suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.

Risk of delayed intracranial hemorrhage in patients on anticoagulation with negative initial imaging.

BACKGROUND: Many institutions obtain a delayed head CT in patients presenting after a ground level fall while on anticoagulation. This study evaluates their risk of delayed ICH. METHODS: Retrospective chart review of 635 patients on anticoagulation who sustained a ground level fall with a negative initial head CT and a GCS above eight. Patients underwent a repeat head CT within 48 h. The ISS was calculated for all patients. RESULTS: Five patients had a delayed ICH. All survived and none required neurosurgical intervention. Patient variables did not have any correlation with development of ICH. Patients with a delayed ICH had a significantly higher ISS. CONCLUSION: Patients on anticoagulation presenting to the hospital after a ground level fall, with a GCS above eight and an initial negative head CT, do not need to undergo repeat imaging. ISS could be used to stratify patients who are at higher risk of delayed ICH.

Association Between Nonselective Beta-Blocker Use and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Without Cirrhosis and Decompensation.

Background: Nonselective beta-blockers (NSBBs) can reduce the incidence or mortality of certain types of cancers, and NSBBs exert a protective effect on hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the potential preventive effect of NSBBs has not yet been investigated in patients with chronic hepatitis B (CHB) who have a high HCC risk regardless of the presence of underlying cirrhosis. Aim: This study evaluated the association between NSBB use and HCC incidence in patients with CHB without cirrhosis and decompensation. Methods: From the 2000 Longitudinal Generation Tracking Database, we enrolled patients who were newly diagnosed as having CHB from January 2001 to December 2011 and then followed them up for at least 5 years. To estimate the causal effect of NSBBs on the time-to-event outcomes of HCC, a marginal Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After adjustment, no significant benefit of HCC risk reduction was observed between the NSBB users and nonusers (adjusted HR, 0.82; 95% CI, 0.52-1.31). The cumulative defined daily dose (cDDD) analysis revealed no significant dose correlation among the three groups [adjusted HR (95% CI): 1.08, (0.56-2.05), 0.54 (0.17-1.77), and 0.76 (0.40-1.42) in the <90 cDDD, 90 to <180 cDDD, and ≥180 cDDD groups, respectively]. Duration-dependent associations were not observed. Multivariable stratified analysis results demonstrated that HCC risk markedly decreased in the patients aged >55 years (adjusted HR, 0.49; 95% CI, 0.25-0.96; p = 0.04). Conclusion: NSBB did not significantly prevent HCC in the patients with CHB infection without cirrhosis and decompensation. This study provided one of valuable results that it is not clinically required to use NSBBs as recommended chemoprevention for HCC in high-risk patients who have CHB.

Warming and shifting phenology accelerate an invasive plant life cycle.

Numerous studies have documented changes in the seasonal timing of organisms' growth and reproduction in response to climate warming. These changes correlate with documented changes in species' abundance, but mechanisms linking these trends remain elusive. We investigated the joint demographic effects of advanced reproductive phenology and warming on a globally invasive plant (Carduus nutans) in a field experiment, documenting a substantial shift toward completion of the life cycle at younger ages. Demographic modeling projected 71% of warmed individuals flower as annuals, compared to 61% under current conditions. As this species only reproduces once, this represents a major acceleration of the life cycle. We project a 15% increase in this invader's population growth rate. We show that rising temperatures accelerate this invasive species' population growth by increasing the average size of reproducing individuals; increasing the proportion of individuals that survive to reproduce; and increasing the fraction that reproduce as annuals. Major increases in population growth in this, and potentially many other, invasive species will threaten food security and require careful planning to avoid significant environmental and economic impacts.