How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression.Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention.Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation.Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia:A Prospective,Randomized,Open,Parallel Controlled and Multicenter Clinical Study

Objective This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia.Methods A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups.Patients in the control group were treated with polysaccharide-iron complex,and those in the experimental group were administered Jianpi Shengxue tablet.After 8 weeks of continuous treatment,the therapeutic outcomes regarding anemia were compared between the two groups.Results After treatment,the red blood cell(RBC)count,hematocrit(HCT),reticulocyte percentage(RET),ferritin(SF),serum iron(SI),transferrin saturation(TSAT),and serum albumin(ALB)all increased(P<0.01),and the clinical symptom score and total iron binding capacity decreased(P<0.01)in the experimental group.Moreover,the improvements in RBC,HCT,RET,SF,SI,TAST,ALB,and clinical symptoms(fatigue,anorexia,dull skin complexion,numbness of hands and feet)in the experimental group were significantly greater than those in the control group(P<0.05).The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group(P<0.01).Conclusion The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia,leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Can propensity score matching replace randomized controlled trials?

Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Electroacupuncture with different waveforms for primary dysmenorrhea:A randomized controlled trial

Objective To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea.Methods This was a prospective,randomized,three-group,parallel-controlled trial.Participants with primary dysmenorrhea were randomly divided into dense-sparse wave,continuous wave,and discontinuous wave groups in a 1:1:1 ratio.Two lateral Ciliao(BL 32)points were used.All three groups started treatment 3–5 days before menstruation,once a day for six sessions per course of treatment,one course of treatment per menstrual cycle,and three menstrual cycles.The primary outcome measure was the proportion with an average visual analog scale(VAS)score reduction of≥50%from baseline for dysmenorrhea in the third menstrual cycle during treatment.The secondary outcome measures included changes in dysmenorrhea VAS scores,Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs.Results The proportion of cases where the average VAS score for dysmenorrhea decreased by≥50%from baseline in the third menstrual cycle was not statistically significant(P>.05).Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea,there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle(P<.05).Additionally,there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture(P<.05).Conclusions Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients.The three groups showed similar results in terms of short-and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs.Regarding achieving immediate analgesia,the dense-sparse wave group was slightly better than the other two groups.

Botulinum toxin type A for treating chronic low back pain:A double blinded randomized control study

BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contributor.The administration of Botulinum toxin type A(BoNT-A)has been found to alleviate back pain by relaxing these stiff muscles.While BoNT-A is approved for use in numerous conditions,a limited number of randomized clinical trials(RCTs)validate its efficacy specifically for treating LBP.AIM To study the safety and the efficacy of BoNT-A in minimizing pain and improving functional outcomes in patients of chronic LBP(CLBP).METHODS In this RCT,adults aged 18-60 years with mechanical LBP persisting for at least six months were enrolled.Participants were allocated to either the Drug group,receiving 200 Ipsen Units(2 mL)of BoNT-A,or the Control group,which received a 2 mL placebo.Over a 2-month follow-up period,both groups were assessed using the Visual Analog Scale(VAS)for pain intensity and the Oswestry Disability Index(ODI)for disability at the start and conclusion of the study.A decrease in pain by 50%was deemed clinically significant.RESULTS The study followed 40 patients for two months,with 20 in each group.A clinically significant reduction in pain was observed in 36 participants.There was a statistically significant decrease in both VAS and ODI scores in the groups at the end of two months.Nonetheless,when comparing the mean score changes,only the reduction in ODI scores(15 in the placebo group vs 16.5 in the drug group,clinically insignificant)was statistically significant(P=0.012),whereas the change in mean VAS scores was not significant(P=0.45).CONCLUSION The study concludes that BoNT-A does not offer a short-term advantage over placebo in reducing pain or improving LBP scores in CLBP patients.

Clinical study on the treatment of acute pancreatitis with external application of Yi-Dan Therapy based on the method of“stagnation requiring dispersion”:study protocol for a randomized controlled trial

Background:Acute pancreatitis is an unpredictable and potentially lethal disease,causing tremendous pain in patients.The initial treatment of acute pancreatitis in modern medicine is supportive,but it is generally ineffective in relieving abdominal pain and distension.Traditional Chinese medicine has been shown to be more effective in regulating the body’s homeostasis and reducing the clinical symptoms of pancreatitis.Yi-Dan ointment,derived from Dahuang-Mudan Decoction,is an effective external ointment for treating acute pancreatitis.The aim of this trial is to investigate the clinical efficacy of Yi-Dan ointment,providing a valuable complement to existing treatment options for pancreatitis.Methods:This is a randomized controlled clinical trial with two parallel groups.Patients in the control group were given basic treatment and nursing for 7 days;in the treatment group,Yi-Dan ointment was applied externally in addition to basic treatment and nursing.The main indicator is the overall efficacy,serum amylase,acute physiology and chronic health evaluationⅡscore,symptom score,inflammatory markers,and classification of computed tomography.Conclusion:The trial results will provide high-quality evidence for Yi-Dan ointment,and provide a complement to existing treatment options for pancreatitis.

基于Random Forest和UHPLC-QTOF-MS^(E)对不同来源龟甲基原的鉴定

目的:基于超高效液相色谱串联四极杆飞行时间质谱(UHPLC-QTOF-MS^(E))分析并经数字量化处理,结合随机森林(Random Forest,RF)算法构建数据辨识模型,以实现中华草龟、巴西龟、台湾龟、鳄鱼龟、鳖甲基原的数字化鉴定。方法:经样品预处理后,对不同来源、不同批次的龟甲进行UPLC-QTOF-MS^(E)分析,并以混合样品为基准进行峰位校正、提取并经量化处理,获取反映多肽离子信息的精确质量数-保留时间数据对(Exact Mass Retention Time,EMRT)。然后基于信息增益率的特征筛选获取重要多肽离子信息,结合随机森林(RF)算法进行数据建模,同时基于内部交叉验证中的准确率(Acc)、精确率(P)、曲线下面积(AUC)等参数进行模型评价。最后基于最优模型进行龟甲基原的鉴定验证分析。结果:基于信息增益率的特征筛选,得到71个特征多肽信息,建立的RF模型具有优秀的辨识效果,准确率、精确率以及AUC均大于0.950且外部鉴定验证的正确率为100.0%。结论:基于UHPLC-QTOF-MS^(E)分析,并结合RF算法能够高效准确地实现不同来源龟甲基原的数字化鉴定,可为龟甲的质量控制及基原考证提供参考和帮助。

Theoretical and experimental study of a bi-stable piezoelectric energy harvester under hybrid galloping and band-limited random excitations

In the practical environment,it is very common for the simultaneous occurrence of base excitation and crosswind.Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascinating.For this purpose,the effects of the wind speed and random excitation level are investigated with the stochastic averaging method(SAM)based on the energy envelope.The results of the analytical prediction are verified with the Monte-Carlo method(MCM).The numerical simulation shows that the introduction of wind can reduce the critical excitation level for triggering an inter-well jump and make a bi-stable energy harvester(BEH)realize the performance enhancement for a weak base excitation.However,as the strength of the wind increases to a particular level,the influence of the random base excitation on the dynamic responses is weakened,and the system exhibits a periodic galloping response.A comparison between a BEH and a linear energy harvester(LEH)indicates that the BEH demonstrates inferior performance for high-speed wind.Relevant experiments are conducted to investigate the validity of the theoretical prediction and numerical simulation.The experimental findings also show that strong random excitation is favorable for the BEH in the range of low wind speeds.However,as the speed of the incoming wind is up to a particular level,the disadvantage of the BEH becomes clear and evident.

Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study

BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study

BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.

一种基于KMeans与Random Forest的异常温升捕捉方法

针对线路老化、线路过载的火灾频发问题,分析了线路老化、线路过载与异常温升之间的关联性,以电流值、线缆温度作为输入,利用KMeans聚类算法划分可能存在异常温升的区间,通过Random Forest算法识别线路过载问题,可以提前通知用户整改线路,预防火灾的发生。

Exploring the Impact of Alcohol Consumption and Smoking on Primary Open Angle Glaucoma: A Mendelian Randomization Study

Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle Glaucoma (POAG). Methods: GWAS data for bibulosity, smoking, and POAG were obtained from the Social Science Genetic Association Consortium website and the IEU OpenGWAS Project website, respectively. Using a P-value threshold of −8, a linkage disequilibrium coefficient (r2) of 0.001, and a linkage disequilibrium region width of 10,000 kb, the data were aggregated, resulting in 6 SNPs for bibulosity and 253 SNPs for smoking. Three regression models, MR-Egger, Weighted Median Estimator (WME), and Random-Effects Inverse-Variance Weighted (IVW) were applied to analyze the causal impact of bibulosity and smoking on POAG. Results: The GWAS data for alcohol consumption and smoking were derived from European populations, while the GWAS data for Primary Open-Angle Glaucoma (POAG) were sourced from East Asian populations, with no gender restrictions. Analysis using three different regression models revealed that neither excessive alcohol consumption nor smoking significantly increased the risk of developing POAG. Specifically, the odds ratios with 95% confidence intervals for the alcohol consumption group were 0.854 (0.597 - 1.221) in MR-Egger regression, 0.922 (0.691 - 1.231) in WME regression, and 0.944 (0.711 - 1.252) in IVW regression. For the smoking group, the odds ratios were 1.146 (0.546 - 2.406) in MR-Egger regression, 0.850 (0.653 - 1.111) in WME regression, and 0.939 (0.780 - 1.131) in IVW regression. Given the significant heterogeneity in the SNPs associated with smoking, the focus was primarily on the results from the IVW regression model. Conclusion: Alcohol consumption and smoking are not significant risk factors for the development of POAG.

Understanding the educational inequalities in suicide attempts and their mediators:a Mendelian randomisation study

Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.

Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization

BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations are causal.METHODS To explore the relationship between dietary intake and the risk of GERD,we extracted appropriate single nucleotide polymorphisms from genome-wide asso-ciation study data on 24 dietary intakes.Three methods were adopted for data analysis:Inverse variance weighting,weighted median methods,and MR-Egger's method.The odds ratio(OR)and 95%confidence interval(CI)were used to eva-luate the causal association between dietary intake and GERD.RESULTS Our univariate Mendelian randomization(UVMR)results showed significant evidence that pork intake(OR,2.83;95%CI:1.76-4.55;P=1.84×10–5),beer intake(OR,2.70,95%CI:2.00-3.64;P=6.54×10–11),non-oily fish intake(OR,2.41;95%CI:1.49-3.91;P=3.59×10–4)have a protective effect on GERD.In addition,dried fruit intake(OR,0.37;95%CI:0.27-0.50;6.27×10–11),red wine intake(OR,0.34;95%CI:0.25-0.47;P=1.90×10-11),cheese intake(OR,0.46;95%CI:0.39-0.55;P=3.73×10-19),bread intake(OR,0.72;95%CI:0.56-0.92;P=0.0009)and cereal intake(OR,0.45;95%CI:0.36-0.57;P=2.07×10-11)were negatively associated with the risk of GERD.There was a suggestive asso-ciation for genetically predicted coffee intake(OR per one SD increase,1.22,95%CI:1.03-1.44;P=0.019).Multi-variate Mendelian randomization further confirmed that dried fruit intake,red wine intake,cheese intake,and cereal intake directly affected GERD.In contrast,the impact of pork intake,beer intake,non-oily fish intake,and bread intake on GERD was partly driven by the common risk factors for GERD.However,after adjusting for all four elements,there was no longer a suggestive association between coffee intake and GERD.CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD,providing new insights for the treatment and prevention of GERD.

Strong invariance principle for a counterbalanced random walk

We study a counterbalanced random walkS_(n)=X_(1)+…+X_(n),which is a discrete time non-Markovian process andX_(n) are given recursively as follows.For n≥2,X_(n) is a new independent sample from some fixed law̸=0 with a fixed probability p,andX_(n)=−X_(v(n))with probability 1−p,where v(n)is a uniform random variable on{1;…;n−1}.We apply martingale method to obtain a strong invariance principle forS_(n).

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.