Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative.

Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients.

BACKGROUND: Several characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk. RESEARCH QUESTION: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types? STUDY DESIGN AND METHODS: A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further. RESULTS: A total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma, in populations with high genetic risk and more detrimental behaviors. INTERPRETATION: Early age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of lung adenocarcinoma, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among female individuals.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and the Risk of Incident Rosacea: Insights from Mendelian Randomization and Cohort Study in the UK Biobank.

BACKGROUND: Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. OBJECTIVE: To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. METHODS: This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. RESULTS: Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). CONCLUSIONS: The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.

Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank.

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

Association of genetic risk and lifestyle with incident adult-onset asthma in the UK Biobank cohort.

Background: Both genetic and lifestyle factors contribute to the development of asthma, but whether unfavourable lifestyle is associated with similar increases in risk of developing asthma among individuals with varying genetic risk levels remains unknown. Methods: A healthy lifestyle score was constructed using body mass index, smoking status, physical activities and dietary pattern to further categorise into ideal, intermediate and poor groups. Genetic risk of asthma was also categorised as three groups based on the tertiles of polygenic risk score established using 212 reported and verified single-nucleotide polymorphisms of European ancestry in the UK Biobank study. We examined the risk of incident asthma related with each lifestyle level in each genetic risk group by Cox regression models. Results: Finally, 327 124 participants without baseline asthma were included, and 157 320 (48.1%) were male. During follow-up, 6238 participants (1.9%) developed asthma. Compared to ideal lifestyle in a low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 3.87 (95% CI, 2.98-5.02) for developing asthma in a high genetic risk group. There was interaction between genetic risk and lifestyle, and the population-attributable fraction of lifestyle and genetic risk were 30.2% and 30.0% respectively. Conclusion: In this large contemporary population, lifestyle and genetic factors jointly play critical roles in the development of asthma, and the effect values of lifestyle on incident adult-onset asthma were greater than that of genetic risk. Our findings highlighted the necessity of a comprehensive intervention for the prevention of asthma despite the genetic risk.

Association of air pollution, genetic risk, and lifestyle with incident adult-onset asthma: A prospective cohort study.

BACKGROUND: Numerous studies have explored the association of air pollution with asthma but have yielded conflicting results. The exact role of air pollution in the incidence of adult-onset asthma and whether this effect is modified by genetic risk, lifestyle, or their interaction remain uncertain. METHODS: We conducted a prospective cohort study on 298,738 participants (aged 37-73 years) registered in the UK Biobank. Cox proportional hazard models were used to evaluate the association of air pollution, including particulate matter (PM2.5, PMcoarse, and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with asthma incidence. We constructed genetic risk and lifestyle scores, assessed whether the impact of air pollution on adult-onset asthma risk was modified by genetic susceptibility or lifestyle factors, and evaluated the identified interactions. RESULTS: We found that each interquartile range increase in annual concentrations of PM2.5, NO2, and NOx was related to 1.04 (95% confidence interval [CI]: 1.01, 1.08), 1.04 (95% CI: 1.00, 1.08), and 1.03 (95% CI: 1.00, 1.06) times the risk of adult-onset asthma, respectively. The size of the effect of air pollution was greater among subpopulations with low genetic risk or unfavorable lifestyles. We also identified an additive interaction effect of air pollution with lifestyle factors, but not with genetic risk, on the risk of adult-onset asthma. CONCLUSION: Our analyses show that air pollution increases the risk of adult-onset asthma, but that the size of the effect is modified by lifestyle and genetic risk. These findings emphasize the need for integrated interventions for environmental pollution by the government as well as adherence to healthy lifestyles to prevent adult-onset asthma.

Association of air pollution and genetic risks with incidence of elderly-onset atopic dermatitis: A prospective cohort study.

BACKGROUND: Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. OBJECTIVES: To explore the association between genes and air pollution on incident elderly-onset AD. MATERIAL AND METHODS: This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. RESULTS: 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. CONCLUSION: Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes.

Associations Between Reproductive Factors and the Risk of Adult-Onset Asthma: A Prospective Cohort Study of European Ancestry.

BACKGROUND: Multiple studies showed sex discrepancies in the prevalence, incidence, and disease control of asthma. The relationships between different reproductive factors and the risk of asthma in females remain uncertain. DESIGN: A prospective cohort study recruited 239,701 female participants from the UK Biobank. The Cox proportional hazard model and multiple adjusted restricted cubic splines were used to evaluate the association between each reproductive factor and the risk of adult-onset asthma. KEY RESULTS: We observed that the association of age at menarche and age of menopause with adult-onset asthma risk presented as U-shaped, with multiple adjusted HRs for age at menarche being 1.129 (95% CI, 1.038-1.228) for ≤ 11 years old and 1.157 (95% CI, 1.058-1.265) for ≥ 15 years old referenced to 13 years old, and for age at menopause being 1.368 (1.237-1.512) for ≤ 46 years old and 1.152 (1.026-1.294) for ≥ 55 years old referenced to 50-52 years old. Early age at first live birth (≤ 20 years old), a greater number of miscarriages (≥ 2) or stillbirths (≥ 2), more children (≥ 4), and shorter reproductive years (≤ 32 years) were associated with elevated risk of asthma. In addition, history of hysterectomy or oophorectomy was associated with increased risk of adult-onset asthma, particularly in those with simultaneous hysterectomy and oophorectomy (HR, 1.239; 95% CI, 1.063-1.445). For exogenous sex hormones, hormone replacement therapy (HR, 1.482; 95% CI, 1.394-1.574) was identified to be associated with elevated risk of adult-onset asthma. CONCLUSIONS: This study not only demonstrated significant associations between multiple reproductive factors and the risk of adult-onset asthma in a female's later life, but also found that history of hysterectomy or oophorectomy, as well as hormone replacement therapy, was linked to an elevated incidence of adult-onset asthma. Our findings highlighted the significance of reproductive factors in the development of asthma in female populations.

Association of outdoor air pollution, lifestyle, genetic factors with the risk of lung cancer: A prospective cohort study.

OBJECTIVES: The effect of air pollution exposure on incident lung cancer remains uncertain, and the modifying role of lifestyle and genetic susceptibility in association between air pollution and lung cancer is ambiguous. METHODS: A total of 367,623 participants from UK biobank cohort were enrolled in the analysis. The concentrations of particle matter (PM2.5, PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), were evaluated by land-use regression model. Cox proportional hazard model was applied to assess the associations between air pollution and incident lung cancer. A lifestyle risk score and a polygenic risk score were established to investigate whether lifestyle and heritable risk could modify the effect of air pollution on lung cancer risk. RESULTS: Per interquartile range (IQR) increment in annual concentrations of PM2.5 (HR = 1.22, 95% CI, 1.15∼1.30), NO2 (HR = 1.19, 95% CI, 1.10∼1.27), and NOx (HR = 1.14, 95% CI, 1.09∼1.20) were associated with increased risk of lung cancer. We observed an additive interaction between air pollution including PM2.5 and NOx and lifestyle or genetic risk. Individuals with high air pollution exposure, poor lifestyle and high genetic risk had the highest risk of incident lung cancer. CONCLUSION: Long-term exposures to air pollution is associated with increased risk of lung cancer, and this effect was modified by lifestyle or genetic risk. Integrated interventions for environmental pollution by government and adherence to healthy lifestyle by individuals are advocated for lung cancer prevention.

Association of Coffee and Tea Consumption with the Risk of Asthma: A Prospective Cohort Study from the UK Biobank.

Background: Previous observational studies investigated the relationship between coffee and tea intake and the risk of asthma, however, the conclusions were inconsistent. Further, the combined effect of coffee and tea consumption on asthma has rarely been studied. Methods: We examined associations between the self-reported intake of tea and coffee and the risk of incident asthma in a total of 424,725 participants aged from 39 to 73 years old from the UK Biobank. Cox proportional hazards models were used to estimate the associations between coffee/tea consumption and incident adult-onset asthma, adjusting for age, sex, race, smoking status, body mass index (BMI), education, and Townsend deprivation index. Results: Cox models with penalized splines showed J-shaped associations of coffee, tea, caffeinated coffee, and caffeine intake from coffee and tea with the risk of adult-onset asthma (p for nonlinear <0.01). Coffee intake of 2 to 3 cups/d (hazard ratio [HR] 0.877, 95% confidence interval [CI] 0.826−0.931) or tea intake of 0.5 to 1 cups/d (HR 0.889, 95% CI 0.816−0.968) or caffeinated coffee intake of 2 to 3 cups/d (HR 0.858, 95% CI 0.806−0.915) or combination caffeine intake from tea and coffee of 160.0 to 235.0 mg per day (HR 0.899, 95% CI 0.842−0.961) were linked with the lowest hazard ratio of incident asthma after adjustment for age, sex, race, smoking status, BMI, qualification, and Townsend deprivation index. Conclusions: Collectively, the study showed light-to-moderate coffee and tea consumption was associated with a reduced risk of adult-onset asthma and controlling total caffeine intake from coffee and tea for a moderate caffeine dose of 160.0 to 305.0 mg/day may be protective against adult-onset asthma. Further investigation on the possible preventive role of caffeine in asthma is warranted.

The efficacy and safety of IL-13 inhibitors in atopic dermatitis: A systematic review and meta-analysis.

Background: Several clinical trials have evaluated the efficacy and safety of interleukin-13 (IL-13) with lebrikizumab and tralokinumab in patients with moderate to severe atopic dermatitis (AD). However, the safety and efficacy of IL-13 inhibitors as a potent biologic for AD remain elusive. Objective: To assess the efficacy and safety of IL-13 inhibitors in moderate to severe AD. Method: Randomized clinical trials (RCTs), comparing IL-13 inhibitors vs placebo treatment in patients with moderate to severe AD, were identified from public database from its inception to November 9th, 2021. The study was registered in PROSPERO (CRD42021254920). Results: Six studies reporting 7 RCTs involving 2946 patients with moderate-to-severe AD were included for the pooled analysis. Compared with placebo, antagonizing IL-13 with lebrikizumab and tralokinumab showed a greater improvement in percentage change of EASI (MD -20.37, 95%CI -32.28, -8.47), and a larger proportion of patients achieving numerical rating scale (NRS) with more than 4-points improvement (RR 1.59, 95%CI 1.23, 2.05). Additionally, IL-13 inhibitors also improved impaired dermatology life quality index (DLQI) (MD -14.49, 95%CI -19.23, -9.75). In terms of safety, both lebrikizumab and tralokinumab were well tolerated, with the except that they were linked to an increased risk of conjunctivitis compared to placebo treatment. Conclusion: Antagonizing IL-13 with lebrikizumab and tralokinumab have demonstrated encouraging clinical efficacy against moderate-to-severe AD with excellent safety profile, albeit they did come with a higher risk of conjunctivitis than placebo treatment. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier ID=CRD42021254920.

Evidence of a Causal Relationship Between Vitamin D Status and Risk of Psoriasis From the UK Biobank Study.

Background: Plenty of observational studies suggested that vitamin D concentrations were associated with psoriasis, but the causality of this relationship was elusive. Objective: To investigate the causal relationship between vitamin D and psoriasis. Methods: Cox proportional hazard model was used to investigate the association between vitamin D status and psoriasis in a prospective cohort study from UK Biobank. Single nucleotide polymorphisms (SNPs) that are strongly associated with circulating 25OHD were constructed as instrumental variables in Mendelian randomization (MR) to determine the causality between vitamin D and psoriasis. Results: During a median follow-up of 10.99 years, we identified 2,856 participants with incident psoriasis. The prospective cohort study demonstrated individuals with 25OHD deficiency (< 25 nmol/L) at baseline were associated with approximately 20% increased risk of incident psoriasis in different categories of sex, age, and body mass index (BMI) after adjusting for covariates. The largest effect size was observed in the obese group (BMI > 30 kg/m2), as 25OHD deficiency presented with 30% additional risk of incident psoriasis compared to those with 25OHD > 50 nmol/L (HR = 0.701; 95% CI: 0.583-0.843; p < 0.001). Additionally, 69 independent SNPs associated with circulating 25OHD level were selected for the MR analysis, and the result suggested that genetically predicted one standard deviation (SD) increment in log-transformed 25OHD was associated with 24% decreased risk of psoriasis (OR = 0.76; 95% CI: 0.60-0.98, p = 0.020). Limitations: The association of 25OHD and severity of psoriasis could not be estimated in the current study. Conclusion: The combined prospective and MR analysis additionally provided evidence that the epidemiologically and genetically determined level of 25OHD conferred an increased risk of psoriasis.

Vitamin D status and asthma, lung function, and hospitalization among British adults.

Background: Vitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear. Objective: To investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults. Methods: Multivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37-73 years old from the UK Biobank. Results: Compared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio (aOR) = 0.936; 95% CI: 0.911-0.962; p < 0.001] and 9.8% (aOR = 0. 0.902; 95% CI: 0.877-0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (ß = 1.328 ml, 95% CI = 0.575-2.080), FVC (ß = 2.018 ml, 95% CI = 1.127-2.908), and FEV1/FVC (ß = 0.006%, 95% CI = 0.002-0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3-19.9% higher odds of current wheeze than insufficient categories (aOR = 0.907; 95% CI: 0.861-0.957; p < 0.001) and optimal categories (aOR = 0.801; 95% CI: 0.759-0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant. Conclusion: Vitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.

Comparing willingness-to-pay and time-trade-off as the measures of burden of psoriasis: A pooled analysis of community, hospital, and web-based samples in China.

Willingness-to-pay (WTP) and time-trade-off (TTO) are widely used as measures of disease burden. However, the sensitivity of the metrics has not been compared in psoriasis. This article aims to report WTP and TTO in Chinese psoriasis patients, and to compare the WTPcure (USD), WTPcontrol (%), and TTO regarding the sensitivity in measuring the burden of psoriasis. Patients were recruited from a community-based cohort, a tertiary hospital, and an online forum. WTP was elicited for two scenarios: WTP for controlling the disease and WTP for curing the disease. WTPcontrol was elicited by asking about the percentage of monthly income that the participant patients would like to pay to fully control the clinical symptoms of psoriasis and WTPcure was elicited as absolute money for curing the disease. The evaluation of WTP and TTO were referred to the Psoriasis Area and Severity Index (PASI) as the indicator of clinical severity, and the Dermatology Life Quality Index (DLQI) as the measure of impaired quality-of-life. Data distribution, concurrent validity, and capability of discriminating moderate-to-severe psoriasis (receiver operating characteristic curve, ROC) were compared among the indices. A total of 479 patients were enrolled from the cohort (88), hospital (175), and web (216). WTPcontrol was significantly higher in patients with PASI>10 than those with PASI<10, while TTO was significantly higher in patients with DLQI>10 than those with DLQI<10. WTP control showed a positive association with PASI in mild psoriasis (r = 0.36, p < 0.001), while TTO showed an inverse correlation to DLQI in different severity subgroups, respectively (r = -0.20, p = 0.001). ROC analysis showed consistent results that WTP control was superior in discriminating patients with PASI>10, while WTP control was better in discriminating DLQI>10. WTPcure demonstrated no significant results. WTPcontrol is superior in detecting mild psoriasis compared to TTO, while TTO is more sensitive in measuring the impaired QoL.

Serum Lipids and Risk of Incident Psoriasis: A Prospective Cohort Study from the UK Biobank Study and Mendelian Randomization Analysis.

The association between dyslipidemia and psoriasis has been studied widely. However, which individual indicators of serum lipids determine an increasing risk of incident psoriasis is still underappreciated in prospective cohorts. On the basis of UK Biobank, we investigate the causal relationship between four serum lipids and incident psoriasis by Cox proportional hazard model and Mendelian randomization analysis. After adjusting for covariates, high-density lipoprotein deficiency (<1.0 mmol/l for men, <1.3 mmol/l for women) and high triglyceride level (≥1.7 mmol/l) at baseline were associated with 16.6% and 10.6% increased risk of incident psoriasis, respectively. The effects were more pronounced in women, with 16.9 and 19.7% additional risk of psoriasis, respectively. The effects in the younger group (aged <60 years) and obese group in women were also more pronounced. No similar effect was observed in low-density lipoprotein and total cholesterol. Our subsequent Mendelian randomization analysis reinforced the main finding that high-density lipoprotein deficiency and high triglyceride cause incident psoriasis genetically. In conclusion, serum high-density lipoprotein/triglyceride levels predict psoriasis, particularly in women, indicating a distinct role of lipids engaging in the pathogenesis of psoriasis modified by sex. More metabolic-targeted, sex-specific management of psoriasis is suggested in the future.

Associations of combined lifestyle and genetic risks with incident psoriasis: A prospective cohort study among UK Biobank participants of European ancestry.

BACKGROUND: Whether the lifestyle is associated with the risk of psoriasis in the presence of different genetic risk levels remains unknown. OBJECTIVE: To examine the gene-behavior interaction in association with incident psoriasis. METHODS: This study is based on the data from the UK Biobank, which recruited 500,000 participants. Genetic risk was categorized into low, intermediate, and high groups. The lifestyle score comprised the body mass index, smoking, physical activity, and diet and was also categorized into the ideal, intermediate, and poor groups. Within each genetic risk group, the risks of incident psoriasis associated with each lifestyle level were investigated and compared with the low genetic risk and ideal lifestyle group. RESULTS: Compared with the low genetic risk and ideal lifestyle group, the poor lifestyle and high genetic risk group was associated with a hazard ratio of up to 4.625 (95% confidence interval [CI], 2.920-7.348) for psoriasis. There was no interaction between genetic risk and lifestyle. The population attributable fractions of lifestyle and genetic risk were 32.2% (95% CI, 25.1%-38.6%) and 13.0% (95% CI, 3.2%-21.8%), respectively. LIMITATIONS: No verification in other independently ascertained populations. CONCLUSION: Lifestyle factors are predictive of the risk of incident psoriasis independent of genetic risk, and the relative impact of lifestyle factors was greater than that of genetic risk.

Effects of co-exposure to multiple metals on children's behavior problems in China.

Exposure to single metals have been linked to childhood behavior problems, But little is known about the effects of metals mixtures on children. We aimed to evaluate associations of multiple metals exposures in urine with childhood behavior in China. For this population-based study, the children eligible for inclusion provided urine samples and their parents agreed to take in-person interview. A total of 831 children were remained from three cities for the final analysis. Urinary metals concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). The childhood behavior scores was calculated by the Conners' Parent Rating Scale (CPRS). Variable selection was achieved by the least absolute shrinkage and selection operator (LASSO) regularization and stepwise regression to for all metals in the study. Linear regression models and Bayesian kernel machine regression (BKMR) were applied to estimate the associations of urinary metals concentrations with children's behavior. In BKMR models, the overall effect of mixture was significantly associated with conduct problems, learning problems and hyperactive index when urinary metals concentrations were all above the 50th percentile compared to all of them at their medians. The models also suggested marginally significant interaction effects of Se and Fe as well as Se and Sb (PSe∗Fe = 0.063; PSe∗Sb = 0.061), with a decline in estimate of Se on learning problems when Sb/Fe levels were relatively high. The concentrations of 22 metals in boys were higher than girls. In summary, multiple metals are associated with an increased risk of childhood behavioral problems in China. Potential interaction effects of Se and Fe as well as Se and Sb on childhood behavior should be taken into consideration.

Perfluoroalkyl substances are linked to incident chronic spontaneous urticaria: A nested case-control study.

Previous studies suggested immunotoxicity of perfluoroalkyl substances (PFASs), but contradictory findings were reported for the associations of PFASs with allergies. The current study aimed to investigate the association of serum PFASs with incident chronic spontaneous urticaria (CSU) in adults. A nested case-control study within a longitudinal cohort of 7051 government employees in China was conducted. Participants with urticaria at the baseline were excluded. During the first follow-up, 70 incident CSU cases were included, and 70 matched healthy controls were randomly selected. In serum samples collected at the baseline, eight PFASs were determined using the UHPLC-MS/MS approach. The median serum concentrations of perfluorobutanoic acid (PFBA) and perfluoroheptanoic acid (PFHpA) were significantly higher in participants with incident CSU. The area under the receiver operating characteristic curve was 0.714 (95% CI: 0.60-0.83) based on the joint prediction by PFBA and PFHpA. The Bayesian kernel machine regression showed a nonlinear positive overall effect of the mixture of PFASs, and identified significant single effects of PFBA and PFHpA. Serum interleukin-4 was significantly higher in the case group at baseline, and was positively associated with PFHpA (r = 0.24). Causal mediation analysis indicated interleukin-4 as a partial mediator (14.8%) in the association of PFHpA with CSU. In conclusion, serum PFASs are associated with an increased risk of incident CSU, and PFBA and PFHpA might be the effective compounds.