Exposure to Air Pollution, Genetic Susceptibility, and Psoriasis Risk in the UK.

Importance: Psoriasis is a common autoinflammatory disease influenced by complex interactions between environmental and genetic factors. The influence of long-term air pollution exposure on psoriasis remains underexplored. Objective: To examine the association between long-term exposure to air pollution and psoriasis and the interaction between air pollution and genetic susceptibility for incident psoriasis. Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank. The analysis sample included individuals who were psoriasis free at baseline and had available data on air pollution exposure. Genetic analyses were restricted to White participants. Data were analyzed between November 1 and December 10, 2023. Exposures: Exposure to nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter with a diameter less than 2.5 µm (PM2.5), and particulate matter with a diameter less than 10 µm (PM10) and genetic susceptibility for psoriasis. Main Outcomes and Measures: To ascertain the association of long-term exposure to NO2, NOx, PM2.5, and PM10 with the risk of psoriasis, a Cox proportional hazards model with time-varying air pollution exposure was used. Cox models were also used to explore the potential interplay between air pollutant exposure and genetic susceptibility for the risk of psoriasis incidence. Results: A total of 474 055 individuals were included, with a mean (SD) age of 56.54 (8.09) years and 257 686 (54.36%) female participants. There were 9186 participants (1.94%) identified as Asian or Asian British, 7542 (1.59%) as Black or Black British, and 446 637 (94.22%) as White European. During a median (IQR) follow-up of 11.91 (11.21-12.59) years, 4031 incident psoriasis events were recorded. There was a positive association between the risk of psoriasis and air pollutant exposure. For every IQR increase in PM2.5, PM10, NO2, and NOx, the hazard ratios (HRs) were 1.41 (95% CI, 1.35-1.46), 1.47 (95% CI, 1.41-1.52), 1.28 (95% CI, 1.23-1.33), and 1.19 (95% CI, 1.14-1.24), respectively. When comparing individuals in the lowest exposure quartile (Q1) with those in the highest exposure quartile (Q4), the multivariate-adjusted HRs were 2.01 (95% CI, 1.83-2.20) for PM2.5, 2.21 (95% CI, 2.02-2.43) for PM10, 1.64 (95% CI, 1.49-1.80) for NO2, and 1.34 (95% CI, 1.22-1.47) for NOx. Moreover, significant interactions between air pollution and genetic predisposition for incident psoriasis were observed. In the subset of 446 637 White individuals, the findings indicated a substantial risk of psoriasis development in participants exposed to the highest quartile of air pollution levels concomitant with high genetic risk compared with those in the lowest quartile of air pollution levels with low genetic risk (PM2.5: HR, 4.11; 95% CI, 3.46-4.90; PM10: HR, 4.29; 95% CI, 3.61-5.08; NO2: HR, 2.95; 95% CI, 2.49-3.50; NOx: HR, 2.44; 95% CI, 2.08-2.87). Conclusions and Relevance: In this prospective cohort study of the association between air pollution and psoriasis, long-term exposure to air pollution was associated with increased psoriasis risk. There was an interaction between air pollution and genetic susceptibility on psoriasis risk.

Impulsivity is a stable, measurable, and predictive psychological trait.

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.

Investigation of high-risk antibiotic resistance bacteria and their associated antibiotic resistance genes in different agricultural soils with biogas slurry from China.

High-risk antibiotic-resistant bacteria (ARB) and their accompanying antibiotic resistance genes (ARGs) seriously threaten public health. As a crucial medium for ARB and ARGs spread, soils with biogas slurry have been widely investigated. However, few studies focused on high-risk multi-drug resistant bacteria (MDRB) and their associated ARGs. This study examined ARB distribution in different agricultural soils with biogas slurry across 12 districts in China. It identified high-risk MDRB in various soil backgrounds, elucidating their resistance and spread mechanism. The findings revealed that diverse cultured ARB were enriched in soils with biogas slurry, especially soil ciprofloxacin ARB, which were enriched (>2.5 times) in 68.4 % of sampling sites. Four high-risk MDRB isolated from Hebei, Zhejiang, Shanxi, and Gansu districts were identified as severe or opportunistic pathogens, which carried abundant mobile genetic elements (MGEs) and 14 known high risk ARGs, including aac(3)-IId, aac(6')-Ib3, aph(6)-Id, aac(6')-Ib3, aadA1, blaOXA-10, blaTEM-1B, dfrA12, dfrA14, cmlA1, sul1, floR, tet(M) and tet(L). The antibiotics accumulation, diverse ARGs and MGEs enrichment, and proliferation of pathogenic bacteria could be potential driving factors of their occurrence and spread. Therefore, the coexistence of the high-risk MDRB and ARGs combined with the associated MGEs in soils with biogas slurry should be further investigated to develop technology and policy for reducing their negative influences on the effectiveness of clinical antibiotics.

Sensitivity-Enhancing Modified Holographic Photopolymer of PQ/PMMA.

Phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymers are potential holographic storage media owing to their high-density storage capacities, low costs, high stability, and negligible shrinkage in volume holographic permanent memory. However, because of the limitations of the substrate, conventional Plexiglas materials do not exhibit a good performance in terms of photosensitivity and molding. In this study, the crosslinked structure of PMMA was modified by introducing a dendrimer monomer, pentaerythritol tetraacrylate (PETA), which increases the photosensitivity of the material 2 times (from ~0.58 cm/J to ~1.18 cm/J), and the diffraction efficiency is increased 1.6 times (from ~50% to ~80%). In addition, the modified material has a superior ability to mold compared to conventional materials. Moreover, the holographic performance enhancement was evaluated in conjunction with a quantum chemical analysis. The doping of PETA resulted in an overall decrease in the energy required for the reaction system of the material, and the activation energy decreased by ~0.5 KJ/mol in the photoreaction stage.

Ambient fine particulate matter is associated with daily outpatient visits for ankylosing spondylitis: A time-series analysis in Beijing, China.

Exposure to ambient fine particulate matter (PM2.5) has a great impact on human body's immune system, but the correlation between PM2.5 and ankylosing spondylitis has not yet been clarified. We extracted 58,600 outpatient visits for ankylosing spondylitis from the Beijing Medical Claim Data for Employees database from 2010 to 2017. The percentage of outpatient visits following PM2.5 concentrations was estimated using generalized additive models with Poisson connections. Increase by 10 µ g/m3, PM2.5 is associated with daily outpatient visits for ankylosing spondylitis. In this test, the average concentration of PM2.5 was 86.8 ± 74.3 µ g/m3. For every 10 µg/m3 increase in PM2.5 concentration, there was a 0.34% (95% CI, 0.26-0.42%) increase in the risk of patients who visited the doctor on the same day. Females and younger patients were most susceptible to the impact of PM2.5 exposure (P＜0.05). This study revealed the relationship between exposure to PM2.5 and ankylosing spondylitis, and future research can further confirm this finding and explore the potential mechanisms.

Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation.

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

To risk or not: The impact of socioeconomic status on preschoolers' risky decision-making for gains and losses.

Disparities in socioeconomic status (SES) may affect individuals' risk preferences, which have important developmental consequences across the lifespan. Yet, previous research has shown inconsistent associations between SES and risky decision-making, and little is known about how this link develops from a young age. The current research is among the first to examine how SES influences preschoolers' risky decisions in both gain and loss frames. Across two studies, children aged 5 to 6 years (total N = 309, 154 boys) were asked to choose between certain and risky options. The risky option was more advantageous, equal to, or less advantageous than the certain option. Study 1 revealed that in the loss frame, high-SES children (n = 84, 44 boys) chose more risky options and were more sensitive to the expected value compared to low-SES children (n = 78, 42 boys), especially when the risk was more advantageous. However, this SES difference was not significant in the gain frame. Supporting the potential causal link between SES and risky decision-making, Study 2 further found that experimentally increasing low-SES children's (n = 68, 30 boys) status by providing additional resources increased their risk-seeking behavior in the loss frame. Overall, our findings suggest an interaction between environmental cues (gain vs. loss) and early life circumstances (SES) in shaping children's risk preferences. RESEARCH HIGHLIGHTS: This research is among the first to examine how school backgrounds and experimentally manipulated SES influence preschoolers' risk preferences in gain and loss frames. Children were more risk-seeking for losses than for gains; this framing effect was stronger in higher-SES than lower-SES children. Lower-SES children exhibited fewer risk-seeking behaviors and decreased sensitivity to the expected value of options for losses, but not for gains. A temporary boost in SES increased children's risk-seeking behavior, but not sensitivity to expected values.

Association Between Peripheral Retinal Defocus and Myopia by Multispectral Refraction Topography in Chinese Children.

Objective: To investigate the association between the peripheral refractive errors of the fundus in different regions and moderate and high myopia. Methods: In this case-control study, 320 children and adolescents aged 6 to 18 years were recruited. Peripheral refractive errors were measured using multispectral retinal refractive topography (MRT). Spherical equivalent (SE) and cylinder errors were classified into low, moderate, and high categories based on the magnitude range. Logistic regression was performed to test the factors associated with myopia. Results: There were 152 participants with low myopia and 168 participants with moderate and high myopia included in the current study. Participants with moderate and high myopia were most likely to be older, with larger axial length (AL), lower SE, less time to watch electronic devices on the weekend, a higher difference between central refractive error and paracentral refractive error from the superior side of the retina (RDV-S), but a smaller difference between the central refractive error and paracentral refractive error from the inferior side of the retina (RDV-I) than those with low myopia (all P <0.05). After logistic analysis, female sex (odds ratio [OR] = 4.14; 95% confidence interval [CI] = 2.16-7.97, P <0.001), AL (OR = 6.88, 95% CI = 4.33-10.93, P <0.001), and RDV-I (OR = 0.52, 95% CI = 0.32-0.86, P = 0.010) were independent factors for moderate and high myopia. Conclusion: Our study demonstrated that the retina peripheral refraction of the eyes (RDV-I) was associated with moderate and high myopia, and RDV-S was only associated with high myopia.

Highly sensitive and repeatable recording photopolymer for holographic data storage containing N-methylpyrrolidone.

The low photosensitivity of phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) severely limits its recording speed for holographic data storage. A high-performance holographic recording medium based on a unique combination of N-methylpyrrolidone (NMP) regulated PQ/PMMA has been developed. A NMP-PQ/PMMA photopolymer with high sensitivity, high diffraction efficiency and negligible volume shrinkage was successfully fabricated by tuning the composition of the PMMA matrix by varying the ratio of NMP to monomers. The photosensitivity is increased by 6.9 times (from 0.27 cm J-1 to 1.86 cm J-1), the diffraction efficiency is increased from 60% to > 80%, and volume shrinkage is decreased by a factor of 2 (from 0.4% to 0.2%). Further investigation revealed that the addition of NMP significantly reduced the molecular weight of PMMA and increased the amount of MMA residuals, while also improving the solubility of PQ molecules. More interestingly, for the first time, the NMP-PQ/PMMA material could record data information repeatedly at least 6 times. The present study elucidates that the introduction of NMP not only modulates the molecular weight of PMMA but also enables the residual monomer MMA to more easily combine with PQ to form a photoproduct for improved holographic performance.

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

The impact of heat waves and cold spells on pneumonia risk: A nationwide study.

Climate change affects human health and has been linked to several infectious diseases in recent year. However, there is limited assessment on the impact of heat waves and cold spells on pneumonia risk. This study aims to examine the association of heat waves and cold spells with daily pneumonia hospitalizations in 168 cities in China. Data on pneumonia hospitalizations between 2014 and 2017 were extracted from a national claim database of 280 million beneficiaries. We consider combining temperature intensity and duration to define heat waves and cold spells.This association was quantified using a quasi-Poisson generalized linear model combined with a distributed lag nonlinear model. Exposure-response curves and potential effect modifiers were also estimated. We found that the peak relative risk (RR) of cold spells on daily hospitalizations for pneumonia was observed in relatively mild cold spells with a threshold below the 3 days at the 2nd percentile (RR = 1.69, 95% CI: 1.46-1.92). The risk of heat waves increased with the thresholds, and the greatest risk was found for extremely heatwave period of 4 days at the 98th percentile (RR = 1.69, 95% CI: 1.46-1.92). Heat waves and cold spells are more likely to adversely affect women. In conclusion, our study provided novel and strong evidence that exposure to heat waves and cold spells was associate with increased hospital visits for pneumonia, especially in females. This is the first national study in China to comprehensively evaluate the influence of heat waves and cold spells on pneumonia risk, and the findings may offer valuable insights into the impact of climate change on public health.

Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma.

Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuroprotective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitors in the treatment of glaucoma from beach to bedside.

1,2,4-Oxadiazole as a potential scaffold in agrochemistry: a review.

N,O-containing heterocycles have been incorporated into various approved pesticides and pesticide candidates. The persistent challenge in contemporary crop protection lies in the continuous pursuit of novel N,O-heterocycle-containing compounds with pesticidal properties. Among them, the 1,2,4-oxadiazole scaffold is one of the most extensively explored heterocycles in new pesticide discovery and development. This review focuses on elucidating the molecular design strategy employed along with highlighting the bioactivity of 1,2,4-oxadiazole derivatives since 2012. Throughout this time frame, tioxazafen and flufenoxadiazam have emerged as prominent examples in which 1,2,4-oxadiazole derivatives were utilized as the core active structure within numerous applications. Additionally, the preparation methods for substituted 1,2,4-oxadiazole derivatives are elaborated upon, and their potential value within agrochemistry is discussed.

Adaptive neural network control for Markov jumping systems against deception attacks.

This paper proposes an innovative approach for mitigating the effects of deception attacks in Markov jumping systems by developing an adaptive neural network control strategy. To address the challenge of dual-mode monitoring mechanisms, two independent Markov chains are used to describe the state changes of the system and the intermittent actuator. By employing a mapping technique, these individual chains are amalgamated into a unified joint Markov chain. Additionally, to effectively approximate the unbounded false signals injected by deception attacks, an adaptive neural network technique is skillfully built. A mode monitoring scheme is implemented to design an asynchronous control law that links the mode information between the joint Markov chain and controller with fewer modes. The paper derives sufficient criteria for the mean-square bounded stability of the resulting system based on Lyapunov theories. Finally, a numerical experiment is conducted to demonstrate the effectiveness of the proposed method.

[Latest Findings in Key Research Areas of Precision Nursing for Chronic Diseases in Older Adults].

The advent of the era of biomedical big data has helped promote the development of precision nursing. Precision nursing for chronic diseases in older adults is an interdisciplinary research field in which accurate individualized data are utilized to carry out early screening and health management of older adult populations at high risk for chronic diseases and early intervention of diseases, which plays an important role in improving the prognosis of diseases and the health level of the older adult population. Herein, we introduced the concept of precision nursing, and discussed the latest research findings in the key areas of precision nursing for chronic diseases in older adults, including precision symptom management in cancer patients and precision nursing in older patients with multimorbidity. At present, research concerning precise symptom management of cancer patients is mainly focused on prediction modelling for risks of symptoms, longitudinal change trajectories, core symptom identification, etc. Investigations in the precise nursing of cancer patients are conducted in the following areas, risk prediction, the timing of interventions, and intervention targets. Research on precision nursing for multimorbidity is mainly focused on assessment of chronic disease multimorbidity, multimorbidity pattern recognition, and health management of multimorbidity. We also discussed potential opportunities and challenges of precision nursing in the future, in order to provide a scientific basis for the improving the practice and theories of precision nursing. In the future, precision nursing will play an ever more important role in uncovering pathogenic information, the diagnosis and treatment of diseases, the health of the research population, and the promotion of medical research.

Short-term exposure to reduced specific-size ambient particulate matter increase the risk of cause-specific cardiovascular disease: A national-wide evidence from hospital admissions.

Evidence for the health effects of ambient PM1 (particulate matter with an aerodynamic diameter ≤ 1 µm) pollution is limited, and it remains unclear whether a smaller particulate matter has a greater impact on human health. We conducted a time-series study in 184 major cities by extracting daily hospital data on admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and stroke between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. City-specific associations were estimated with over-dispersed generalized additive models. A random-effects meta-analysis was used to estimate regional and national average associations. We conducted stratified and meta-regression analyses to explore potential effect modifiers of the association. We recorded 8.83 million cardiovascular admissions during the study period. At the national-average level, a 10-µg/m3 increase in same-day PM1, PM2.5(particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10(particulate matter with an aerodynamic diameter ≤ 10 µm) concentrations corresponded to a 1.14% (95% confidence interval 0.88-1.41%), 0.55% (0.40-0.70%), and 0.45% (0.36-0.55%) increase in cardiovascular admissions, respectively. PM1 exposure was also positively associated with all cardiovascular disease subtypes, including ischemic heart disease (1.28% change; 0.99-1.56%), heart failure (1.30% change; 0.70-1.91%), heart rhythm disturbances (1.11% change; 0.65-1.58%), and ischemic stroke (1.29% change; 0.88-1.71%). The associations between PM1 and cardiovascular admissions were stronger in cities with lower PM1 levels, higher air temperatures and relative humidity, as well as in subgroups with elder age (all P < 0.05). This study provides robust evidence of short-term associations between PM1 concentrations and increased hospital admissions for all major cardiovascular diseases in China. Our findings suggest a greater short-term impact on cardiovascular risk from PM1 in comparison to PM2.5 and PM10.

Association of Metformin Use with Iron Deficiency Anemia in Urban Chinese Patients with Type 2 Diabetes.

BACKGROUND: Previous evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk in patients with type 2 diabetes (T2D) in Beijing, China. METHODS: Overall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs). RESULTS: The study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of <20%, 20-79%, and ≥80% was 0.43 (0.38, 0.48), 0.37 (0.34, 0.42), and 0.91 (0.85, 0.98), respectively, compared to the non-metformin group. We also performed subgroup analyses and sensitivity analyses: the incidence of IDA in the metformin group was lower than that in the non-metformin group in all subgroups, and the protective effect was more significant in subgroups of patients aged ≥65, with Charlson comorbidity index (CCI) ≥2, and with gastric acid inhibitor use. CONCLUSIONS: In Chinese patients with T2DM, metformin treatment was associated with a decreased risk of IDA admission, and this risk responded positively to the proportion of days covered by metformin. These findings suggest that metformin may have a pleiotropic effect on IDA in patients with type 2 diabetes. Our study has important clinical implications for the management of patients with diabetes and other conditions that increase the risk of IDA.

Is statin therapy after ischaemic stroke associated with increased intracerebral hemorrhage? The association may be dependent on intensity of statin therapy.

BACKGROUND: There has been concern that statin therapy may be associated with an increased risk of intracerebral hemorrhage (ICH). We investigated whether the intensity and type of statin therapy instituted after ischemic stroke (IS) were associated with risk of future ICH in a region of northern China with a high incidence of stroke. METHODS: Newly diagnosed IS patients who were not treated with lipid-lowering drugs in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. The primary exposure variable was any statin prescription within 1 month of the first documented stroke diagnosis. High-intensity statin therapy was defined as atorvastatin ⩾ 80 mg, simvastatin ⩾ 80 mg, pravastatin ⩾ 40 mg, and rosuvastatin ⩾ 20 mg per day or equivalent combination. An adjusted Cox proportional hazards model was used to estimate the hazard ratio (HR) for ICH during follow-up in groups exposed and not exposed to statins. RESULTS: Of 62,252 participants with IS and 628 ICH readmissions were recorded during a median follow-up of 3.17 years. The risk of ICH among statin users (N = 43,434) was similar to that among nonusers (N = 18,818) with an adjusted HR and 95% confidence interval (CI) of 0.86 (0.73, 1.02). Compared with non-statin therapy, patients with low/moderate-intensity therapy had a lower risk of ICH (0.62: 0.52, 0.75), while patients with high-intensity therapy had a substantially higher risk (2.12: 1.72, 2.62). For patients with different types of statin therapy, adherence to rosuvastatin had the lowest risk of ICH compared to adherence to atorvastatin (0.46: 0.34, 0.63), followed by simvastatin (0.60: 0.45, 0.81). CONCLUSION: In patients with IS, any statin therapy was not associated with an increased risk of ICH. However there appeared to be differential risk according to the dose of statin with high-intensity statin therapy being associated with an increased risk of ICH, while low/moderate-intensity therapy was associated with a lower risk.

Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China.

Background: Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China. Methods: All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results: Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69). Conclusions: In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.