Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics betw...Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.展开更多
Mendelian randomisation(MR)is a widely used method that employs genetic variants as instrumental variables(IVs,also referred to as genetic instruments below and they represent eligible genetic variants in MR)from geno...Mendelian randomisation(MR)is a widely used method that employs genetic variants as instrumental variables(IVs,also referred to as genetic instruments below and they represent eligible genetic variants in MR)from genome-wide association studies(GWAS)to explore the causative relationship between putative risk factors(ie,exposures)and outcomes.1 According to a Web of Science literature search conducted at the end of 2024,the number of related publications has grown exponentially,reaching 3545 in 2023 and 6607 in 2024(figure 1).Almost simultaneously,we observed a peak of citations from 2019 to 2021,which reflected the popularity and acknowledgement of papers published in these 3 years.However,a decline in citations has been witnessed from 2022 and here are two possible explanations for it:(1)papers published in 2022 or later only have two or fewer years to be cited,and it can lead to fewer citations absolutely;(2)some papers published from 2022 are of low quality and may even be redundant analyses,thus,they are less likely to be cited.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution o...Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.展开更多
Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes.However,if performed without...Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes.However,if performed without critical thought,we may simply have replaced one set of implausible assumptions(no unmeasured confounding or reverse causation)with another set of implausible assumptions(no pleiotropy or other instrument invalidity).The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables.Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy;in general,a biologically motivated strategy is preferred.In this review,we discuss various ways of implementing a biologically motivated selection strategy:using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels,using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy.In some cases,a genome-wide analysis can provide important complementary evidence,even when its reliability is questionable.In other cases,a biologically-motivated analysis may not be possible.The choice of genetic variants must be informed by biological and functional considerations where possible,requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.展开更多
Background Despite studies confirming that patients with inflammatory bowel disease(IBD)present with dyslipidaemia,the associations between IBD and the serum lipid profile have not been determined.The present study ai...Background Despite studies confirming that patients with inflammatory bowel disease(IBD)present with dyslipidaemia,the associations between IBD and the serum lipid profile have not been determined.The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interactions between them.Methods Two-sample Mendelian randomisation(MR)analysis was performed to investigate the causal links between total cholesterol(TC),total triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A(Apo A),apolipoprotein B(Apo B)and lipoprotein(a)(Lp(a))and IBD.The study was carried out using the R TwoSampleMR and Mendelian randomisation packages.Results All MR methods,including the weighted median,weighted mode,inverse-variance weighted model,MR-PRESSO,contamination mixture and MR Egger,supported a null causal relationship between TG,TC,HDL-C,LDL-C,Apo A,Apo B and Lp(a)and between IBD,Crohn’s disease and ulcerative colitis.Null causal effects of lipid indices on IBD were validated through independent genome-wide association studies(GWAS),indicating that the findings are robust.Conclusion Our findings suggest that none of the seven lipid indices may be a potential risk factor for the onset of IBD.However,additional research is needed since our MR analyses cannot assess the potential non-linear causal relationship between serum lipids and IBD.展开更多
Stratified cluster randomisation trial design is widely employed in biomedical research and cluster size has been frequently used as the stratifying factor.Conventional sample size calculation methods have assumed the...Stratified cluster randomisation trial design is widely employed in biomedical research and cluster size has been frequently used as the stratifying factor.Conventional sample size calculation methods have assumed the cluster sizes to be constant within each stratum,which is rarely true in practice.Ignoring the random variability in cluster size leads to underestimated sample sizes and underpowered clinical trials.In this study,we proposed to directly incorporate the variability in cluster size(represented by coefficient of variability)into sample size calculation.This approach provides closed-form sample size formulas,and is flexible to accommodate arbitrary randomisation ratio and varying numbers of clusters across strata.Simulation study shows that the proposed approach achieves desired power and type I error over a wide spectrum of design configurations,including different distributions of cluster sizes.An application example is presented.展开更多
BACKGROUND Bismuth quadruple therapy(BQT)induces troublesome gastrointestinal side effects that reduce adherence and efficacy.AIM To evaluate multistrain probiotics efficacy for alleviating gastrointestinal sym-ptoms ...BACKGROUND Bismuth quadruple therapy(BQT)induces troublesome gastrointestinal side effects that reduce adherence and efficacy.AIM To evaluate multistrain probiotics efficacy for alleviating gastrointestinal sym-ptoms during BQT for Helicobacter pylori(H.pylori)eradication.METHODS One hundred seventy-four adults(18-60 years)with confirmed H.pylori infections between July 2022 and December 2023 were randomised to receive BQT plus a multispecies probiotic(n=89)or a maltodextrin placebo(n=85)for 4 weeks.Gastrointestinal Symptom Rating Scale(GSRS)and Bristol Stool Classification Scale scores were collected at baseline,2,4 and 8 weeks;eradication was assessed 8 weeks post-treatment.Intention-to-treat analysis used multiple imputation and SPSS 26.0.RESULTS After 8 weeks,GSRS scores(all dimensions and total)decreased significantly compared with those at baseline.ITT analysis showed significantly greater reductions for the intervention vs the placebo in reflux by week 2,total/diarrhea scores by week 4,and total/dyspepsia scores by week 8.Probiotics provided no protective effect against gastrointestinal symptoms at week 2 but showed significant protection at weeks 4 and 8.Both groups reported decreased diarrhea/constipation-type stools and increased normal-type stools post-intervention.H.pylori eradication rates were slightly higher for the intervention group(88.8%)than for the placebo group(84.7%),but the difference was not significant(P=0.430).CONCLUSION Multistrain probiotics significantly relieved BQT-associated gastrointestinal symptoms without affecting era-dication success.展开更多
Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exerc...Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exercise(RE)interventions in older adults with mild cognitive impairment(MCI).Methods This study is a 6-month pilot three-arm randomised controlled trial.Eligible participants(n=108)were recruited and randomised to the AE group,RE group or control(CON)group with a 1:1:1 ratio.Interventions were delivered at home with remote supervision.We evaluated participants’global cognition,memory,executive function,attention,physical activity levels,physical performance and muscle strength of limbs at baseline,3 months(T1)and 6 months(T2)after randomisation.A linear mixed-effects model was adopted for data analyses after controlling for covariates.Tukey’s method was used for adjusting for multiple comparisons.Sensitivity analyses were performed after excluding individuals with low compliance rates.Results 15(13.89%)participants dropped out.The median compliance rates in the AE group and RE group were 67.31%and 93.27%,respectively.After adjusting for covariates,the scores of the Alzheimer’s Disease Assessment Scale-Cognitive subscale in the AE group decreased by 2.04(95%confidence interval(CI)−3.41 to−0.67,t=−2.94,p=0.004)and 1.53(95%CI−2.88 to−0.17,t=−2.22,p=0.028)points more than those in the CON group at T1 and T2,respectively.The effects of AE were still significant at T1(estimate=−1.70,95%CI−3.20 to−0.21,t=−2.69,p=0.021),but lost statistical significance at T2 after adjusting for multiple comparisons.As for executive function,the Stroop time interference in the RE group decreased by 11.76 s(95%CI−21.62 to−1.90,t=−2.81,p=0.015)more than that in the AE group at T2 after Tukey’s adjustment.No other significant effects on cognitive functions were found.Conclusions Both remotely supervised AE and RE programmes are feasible in older adults with MCI.AE has positive effects on global cognition,and RE improves executive function.展开更多
Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network con...Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression.Aim This study aimed to identify default mode network(DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression.Methods Data from a randomised controlled trial of iTBS in depression(n=82)were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN.Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment.Furthermore,the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated.Results Two distinct subgroups were identified.Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex,while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule.No main effect for subgroup,treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms.A significant subgroup×treatment interaction related to symbol coding improvement was detected(F=5.22,p=0.026).Within subgroup 1,the active group showed significantly greater improvement in symbol coding compared with the sham group(t=2.30,p=0.028),while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding(R2=0.35,RMSE(root-mean-square error)=5.72,p=0.013).Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions.展开更多
Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mediated mainly by immunoglobulin E (IgE) in atopic individuals after exposure to allergens, with the typical symptoms of par...Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mediated mainly by immunoglobulin E (IgE) in atopic individuals after exposure to allergens, with the typical symptoms of paroxysmal sneezing, watery runny nose, itchy nose and nasal congestion. Mendelian randomization (MR), an innovative epidemiological approach that uses common genetic variants as instrumental variables for exposure, thus enabling prediction of their causal relationship with outcomes, has been widely used in recent years in studies related to AR. This paper provides a review of the method and its progress in the field of allergic rhinitis research.展开更多
AIM:To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation. METHODS:The MEDLINE,EMBASE,CINAHL,and Cochrane Library databases were searc...AIM:To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation. METHODS:The MEDLINE,EMBASE,CINAHL,and Cochrane Library databases were searched in May 2009 for randomised controlled trials(RCTs)performed in paediatric or adult populations related to the study aim. RESULTS:We included five RCTs with a total of 377 subjects(194 in the experimental group and 183 in the control group).The participants were adults (three RCTs,n=266)and children(two RCTs,n= 111)with constipation.In adults,data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010,Lactobacillus casei Shirota,and Escherichia coli Nissle 1917 on defecation frequency and stool consistency.In children,L.casei rhamnosusLcr35,but not L.rhamnosus GG,showed a beneficial effect. CONCLUSION:Until more data are available,we believe the use of probiotics for the treatment of constipation condition should be considered investigational.展开更多
Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional prac...Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional practice of fasting patients until the resumption of bowel function threatens to further contribute to the malnutrition experienced by these patients.Furthermore,the rationale behind this traditional practice has been rendered obsolete through developments in anaesthetic agents and changes to postoperative analgesia practices.Conversely,there is a growing body of literature that consistently demonstrates that providing oral or tube feeding proximal to the anastomosis within 24 h postoperatively,is not only safe,but might be associated with significant benefits to the postoperative course.Early post operative feeding should therefore be adopted as a standard of care in oncology patients undergoing gastrointestinal resections.展开更多
Surgical resection remains the mainstay of treatment for gastric cancer.Laparoscopic assisted gastrectomy has failed to gain universal acceptance as an alternative to the open approach for a number of reasons,one of w...Surgical resection remains the mainstay of treatment for gastric cancer.Laparoscopic assisted gastrectomy has failed to gain universal acceptance as an alternative to the open approach for a number of reasons,one of which includes the issue of oncological radicality in terms of lymph node dissection.Nodal status,which is one of the most crucial and independent predictors of patient survival,therefore has been examined both in single institutional trials and also in randomised controlled trials especially on early gastric cancer.The issue of oncological adequacy for laparoscopic lymph node harvesting for advanced gastric cancer remains a contentious issue because of the unique challenges it poses in terms of complexity,safety and time,and also the lack of randomised controlled trials in this area.It is thus imperative that good quality multicentre randomised controlled trials are designed to investigate the benef its of extended lymphadenectomy in the setting of laparoscopic surgery,especially for advanced gastric cancer and its impact on both short and long term survival.展开更多
AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necess...AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necessitate 6 wk wrist immobilisation.METHODS A prospective,randomised controlled single-centre trial was conducted with 56 patients who had a displaced radius fracture were randomised to treatment either with a volar locking plate(n=29),or another treatment modality(n=27;cast immobilisation with or without wires or external fixator).Outcomes were measured at 12 wk.Functional outcome scores measured were the Patient-Rated Wrist Evaluation(PRWE)Score;Disabilities of the Arm,Shoulder and Hand and activities of daily living(ADLs).Clinical outcomes were wrist range of motion and grip strength.Radiographic parameters were volar inclination and ulnar variance.RESULTS Patients in the volar locking plate group had significantly better PRWE scores,ADL scores,grip strength and range of extension at three months compared with the control group.All radiological parameters were significantly better in the volar locking plate group at 3 mo.CONCLUSION The present study suggests that volar locking plates produced significantly better functional and clinical outcomes at 3 mo compared with other treatment modalities.Anatomical reduction was significantly more likely to be preserved in the plating group.Level of evidence:Ⅱ.展开更多
AIM To compare high definition white light endoscopy and bright narrow band imaging for colon polyps' detection rates. METHODS Patients were randomised to high definition white light endoscopy(HD-WLE) or the brigh...AIM To compare high definition white light endoscopy and bright narrow band imaging for colon polyps' detection rates. METHODS Patients were randomised to high definition white light endoscopy(HD-WLE) or the bright narrow band imaging(b NBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using b NBI with dual focus(b NBI-DF) according to the Sano's classification. The primary outcome was to compare adenoma detection rates(ADRs) between the two arms. The secondary outcome was to assess the negative predictive value(NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions.RESULTS A total of 1006 patients were randomised to HD-WLE(n = 511) or b NBI(n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in b NBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time(OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of b NBI was associated with a reduced ADR(OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps(86%) in both arms were predicted with high confidence. The sensitivity(Sn), specificity(Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using b NBI-DF for diminutive rectal polyps was 91.0%.CONCLUSION ADRs did not differ between b NBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. b NBI surpassed the PIVI threshold for diminutive polyps.展开更多
Background Hyperprolactinaemia is a common adverse effect of antipsychotics （APs）. The results of Peony-Glycyrrhiza decoction （PGD） as a potentially useful adjunctivetreatment for hyperprolactinaemia are inconsis...Background Hyperprolactinaemia is a common adverse effect of antipsychotics （APs）. The results of Peony-Glycyrrhiza decoction （PGD） as a potentially useful adjunctivetreatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials （RCTs） examined the effcacy and safety of adjunctive PGDtherapy for AP-induced hyperprolactinaemia.Methods English （PubMed, Embase, Cochrane Library, PsycINFO） and Chinese （Chinese National Knowledge Infrastructure, Wanfang Data） databases were systematicallysearched up to 10 June 2018. The inclusion criteria were based on PICOS-Participants： adult patients with schizophrenia; Intervention： PGD plus APs; Comparison： APs plus placebo or AP monotherapy; Outcomes： effcacy and safety; Study design： RCTs. The weighted mean difference （WMD） and risk ratio （RR） along with their 95% CIs were calculated using Review Manager （RevMan） V.5.3 software.Results Five RCTs （n=450） were included and analysed. Two RCTs （n=140） were double-blind and four RCTs （n=409） reported ‘random’ assignment with specifc description. The PGD group showed a signifcantly lower serum prolactin level at endpoint than the control group （n=380, WMD： ？32.69 ng/mL （95% CI -41.66 to 23.72）, p〈0.00001, I2=97%）. Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale （n=403, WMD： -0.62 （95% CI -2.38 to 1.15）, p=0.49, I^2=0%）. There were similar rates of all-cause discontinuation （n=330, RR 0.93 （95% CI 0.63 to 1.37）, p=0.71, I^2=0%） and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low’ （14.3%）, ‘low’ （42.8%）, ‘moderate’ （14.3%）, to ‘high’ （28.6%）.Conclusions Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactin-induced symptoms without signifcant adverse events in adult patients with AP-induced hyperprolactinaemia. High-quality RCTs with longer duration are needed to confrm these fndings.展开更多
Objective: To report our experience of attempting a randomised controlled trial of an intensive lifestyle intervention for early type 2 diabetes delivered in a residential setting. Methods: We established a trial requ...Objective: To report our experience of attempting a randomised controlled trial of an intensive lifestyle intervention for early type 2 diabetes delivered in a residential setting. Methods: We established a trial requiring 84 participants (46 standard care and 38 intervention) to detect a 1% difference in HbA1c between intervention and control groups at 12 months, allowing for attrition. Ethics approval was obtained from Monash University. Results: The study was abandoned after five months of consistent promotion due to recruitment failure (four subjects recruited). Conclusion: It appears to be difficult for patients with diabetes to commit to a live-in period of education regarding lifestyle modification as a means of treating the illness. We recommend better education of patients and their doctors about the potential health benefits of lifestyle change to manage type 2 diabetes, and further research into novel methods of delivering lifestyle advice which are both effective and sustainable.展开更多
The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years.Their role appeared clear at the start of this century.The Helsinki Heart Study and Veterans Affairs High-Density Chole...The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years.Their role appeared clear at the start of this century.The Helsinki Heart Study and Veterans Affairs High-Density Cholesterol Intervention Trial suggested significant benefit,especially in patients with atherogenic dyslipidaemia.However,this clarity disintegrated following the negative outcomes reported by the Bezafibrate Infarction Prevention,Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes randomised controlled trials.In this review we discuss these and other relevant trials and consider patient subgroups such as those with the metabolic syndrome and those needing treatment to prevent the microvascular complications associated with diabetes in whom fibrates may be useful.We also discuss observations from our group that may provide some explanation for the varying outcomes reported in large trials.The actions of fibrates in patients who are also on statins are interesting and appear to differ from those in patients not on statins.Understanding this is key as statins are the primary lipid lowering agents and likely to occupy that position for the foreseeable future.We also present other features of fibrate treatment we have observed in our clinical practice;changes in creatinine,liver function tests and the paradoxical high density lipoprotein reduction.Our purpose is to provide enough data for the reader to make objective decisions in their own clinical practice regarding fibrate use.展开更多
Objective:To evaluate the efficacy and safety of Baimai ointment in patients with lumbar disc herniation(LDH).Methods:This study presents a prospective randomized,double-blind,placebo-controlled,multicenter clinical t...Objective:To evaluate the efficacy and safety of Baimai ointment in patients with lumbar disc herniation(LDH).Methods:This study presents a prospective randomized,double-blind,placebo-controlled,multicenter clinical trial protocol.A total of 194 cases will be employed,with a 1:1 allocation ratio for each group.Patients will receive either Baimai ointment or placebo over a 14-day treatment period,which will be followed by a 1-week follow-up period.Visual analogue scale scores will be used for the level of pain,the Japanese Orthopedic Association score will be measured primarily to determine the functional status,the Likert scale will be graded for the level of numbness,and rescue therapy use and compliance with health education will be recorded.Laboratory tests and adverse event records will also be applied for safety assessments.Discussion:In summary,this trial will assess the clinical efficacy and safety of Baimai ointment for LDH for the first time.The use of a placebo has the advantage of precluding anticipatory biases resulting from inadequate blinding.Outcome assessors,data managers,statisticians,and all related study staff will be blinded to avoid any bias caused by subjective factors in the study subjects and investigators.Valuable information for clinical LDH treatment and future research on Baimai ointment will be generated from the findings.展开更多
基金supported by the National Natural Science Foundation of China(82071500,82271540,32370724,82401759,81871055,32070679)Shanghai Clinical Research Center for Mental Health(19MC1911100)+11 种基金Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)Shanghai Municipal Administrator of Traditional Chinese Medicine(ZY-(2021-2023)-0207-01)Shanghai Municipal Health Commission Collaborative Innovation Group(2024CXJQ03)Shanghai Science and Technology Innovation Action Program(24JS2840400,24ZR1439900,21Y11921100)Shanghai Municipal Science and Technology Major Project,the National Key R&D Program of China(2023YFA0913804,2024YFA0916603,2022FYC2503300)the Program of Shanghai Academic/Technology Research Leader(21XD1423300)Shanghai Pujiang Program(21PJD063)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Shanghai Municipal Commission of Education(2024AIZD016)the National Key R&D Program of China(2019YFA0905400,2017YFC0908105,2021YFC2702100)National Program for Support of Top-Notch Young Professionals,Taishan Scholar Program of Shandong Province(tstp20240526)the Natural Science Foundation of Shandong Province(ZR2019YQ14,YDZX2021009,2021ZDSYS06).
文摘Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.
文摘Mendelian randomisation(MR)is a widely used method that employs genetic variants as instrumental variables(IVs,also referred to as genetic instruments below and they represent eligible genetic variants in MR)from genome-wide association studies(GWAS)to explore the causative relationship between putative risk factors(ie,exposures)and outcomes.1 According to a Web of Science literature search conducted at the end of 2024,the number of related publications has grown exponentially,reaching 3545 in 2023 and 6607 in 2024(figure 1).Almost simultaneously,we observed a peak of citations from 2019 to 2021,which reflected the popularity and acknowledgement of papers published in these 3 years.However,a decline in citations has been witnessed from 2022 and here are two possible explanations for it:(1)papers published in 2022 or later only have two or fewer years to be cited,and it can lead to fewer citations absolutely;(2)some papers published from 2022 are of low quality and may even be redundant analyses,thus,they are less likely to be cited.
基金supported by Seed Fund for Basic Science(2302101604),the University of Hong Kong.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.
基金SB is supported by the Wellcome Trust(225790/Z/22/Z)the United Kingdom Research and Innovation Medical Research Council(MC_UU_00002/7)This research was supported by the National Institute for Health Research Cambridge Biomedical Research Centre(NIHR203312).
文摘Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes.However,if performed without critical thought,we may simply have replaced one set of implausible assumptions(no unmeasured confounding or reverse causation)with another set of implausible assumptions(no pleiotropy or other instrument invalidity).The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables.Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy;in general,a biologically motivated strategy is preferred.In this review,we discuss various ways of implementing a biologically motivated selection strategy:using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels,using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy.In some cases,a genome-wide analysis can provide important complementary evidence,even when its reliability is questionable.In other cases,a biologically-motivated analysis may not be possible.The choice of genetic variants must be informed by biological and functional considerations where possible,requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.
基金funded by Department of Science and Technology of Jilin Province(Grant numbers:20200201316JC and YDZJ202201ZYTS121).
文摘Background Despite studies confirming that patients with inflammatory bowel disease(IBD)present with dyslipidaemia,the associations between IBD and the serum lipid profile have not been determined.The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interactions between them.Methods Two-sample Mendelian randomisation(MR)analysis was performed to investigate the causal links between total cholesterol(TC),total triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A(Apo A),apolipoprotein B(Apo B)and lipoprotein(a)(Lp(a))and IBD.The study was carried out using the R TwoSampleMR and Mendelian randomisation packages.Results All MR methods,including the weighted median,weighted mode,inverse-variance weighted model,MR-PRESSO,contamination mixture and MR Egger,supported a null causal relationship between TG,TC,HDL-C,LDL-C,Apo A,Apo B and Lp(a)and between IBD,Crohn’s disease and ulcerative colitis.Null causal effects of lipid indices on IBD were validated through independent genome-wide association studies(GWAS),indicating that the findings are robust.Conclusion Our findings suggest that none of the seven lipid indices may be a potential risk factor for the onset of IBD.However,additional research is needed since our MR analyses cannot assess the potential non-linear causal relationship between serum lipids and IBD.
基金The work was supported in part by NIH grant[1UL1TR001105]AHRQ grant[R24HS22418]+1 种基金CPRIT grants[RP110562-C1]and[RP120670-C1]NSF grant[IIS-1302497-04].
文摘Stratified cluster randomisation trial design is widely employed in biomedical research and cluster size has been frequently used as the stratifying factor.Conventional sample size calculation methods have assumed the cluster sizes to be constant within each stratum,which is rarely true in practice.Ignoring the random variability in cluster size leads to underestimated sample sizes and underpowered clinical trials.In this study,we proposed to directly incorporate the variability in cluster size(represented by coefficient of variability)into sample size calculation.This approach provides closed-form sample size formulas,and is flexible to accommodate arbitrary randomisation ratio and varying numbers of clusters across strata.Simulation study shows that the proposed approach achieves desired power and type I error over a wide spectrum of design configurations,including different distributions of cluster sizes.An application example is presented.
文摘BACKGROUND Bismuth quadruple therapy(BQT)induces troublesome gastrointestinal side effects that reduce adherence and efficacy.AIM To evaluate multistrain probiotics efficacy for alleviating gastrointestinal sym-ptoms during BQT for Helicobacter pylori(H.pylori)eradication.METHODS One hundred seventy-four adults(18-60 years)with confirmed H.pylori infections between July 2022 and December 2023 were randomised to receive BQT plus a multispecies probiotic(n=89)or a maltodextrin placebo(n=85)for 4 weeks.Gastrointestinal Symptom Rating Scale(GSRS)and Bristol Stool Classification Scale scores were collected at baseline,2,4 and 8 weeks;eradication was assessed 8 weeks post-treatment.Intention-to-treat analysis used multiple imputation and SPSS 26.0.RESULTS After 8 weeks,GSRS scores(all dimensions and total)decreased significantly compared with those at baseline.ITT analysis showed significantly greater reductions for the intervention vs the placebo in reflux by week 2,total/diarrhea scores by week 4,and total/dyspepsia scores by week 8.Probiotics provided no protective effect against gastrointestinal symptoms at week 2 but showed significant protection at weeks 4 and 8.Both groups reported decreased diarrhea/constipation-type stools and increased normal-type stools post-intervention.H.pylori eradication rates were slightly higher for the intervention group(88.8%)than for the placebo group(84.7%),but the difference was not significant(P=0.430).CONCLUSION Multistrain probiotics significantly relieved BQT-associated gastrointestinal symptoms without affecting era-dication success.
基金funded by the National Natural Science Foundation of China(81871854,72374014)the National Key R&D Program of China(2020YFC2008804)+1 种基金the Shanghai Jiao Tong University Young Talent Cultivation Program in Liberal Arts(2024QN041)the Shanghai Jiao Tong University School of Medicine:Nursing Development Program(SJTUHLXK2024).
文摘Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exercise(RE)interventions in older adults with mild cognitive impairment(MCI).Methods This study is a 6-month pilot three-arm randomised controlled trial.Eligible participants(n=108)were recruited and randomised to the AE group,RE group or control(CON)group with a 1:1:1 ratio.Interventions were delivered at home with remote supervision.We evaluated participants’global cognition,memory,executive function,attention,physical activity levels,physical performance and muscle strength of limbs at baseline,3 months(T1)and 6 months(T2)after randomisation.A linear mixed-effects model was adopted for data analyses after controlling for covariates.Tukey’s method was used for adjusting for multiple comparisons.Sensitivity analyses were performed after excluding individuals with low compliance rates.Results 15(13.89%)participants dropped out.The median compliance rates in the AE group and RE group were 67.31%and 93.27%,respectively.After adjusting for covariates,the scores of the Alzheimer’s Disease Assessment Scale-Cognitive subscale in the AE group decreased by 2.04(95%confidence interval(CI)−3.41 to−0.67,t=−2.94,p=0.004)and 1.53(95%CI−2.88 to−0.17,t=−2.22,p=0.028)points more than those in the CON group at T1 and T2,respectively.The effects of AE were still significant at T1(estimate=−1.70,95%CI−3.20 to−0.21,t=−2.69,p=0.021),but lost statistical significance at T2 after adjusting for multiple comparisons.As for executive function,the Stroop time interference in the RE group decreased by 11.76 s(95%CI−21.62 to−1.90,t=−2.81,p=0.015)more than that in the AE group at T2 after Tukey’s adjustment.No other significant effects on cognitive functions were found.Conclusions Both remotely supervised AE and RE programmes are feasible in older adults with MCI.AE has positive effects on global cognition,and RE improves executive function.
基金supported by the Guangzhou Municipal Key Discipline in Medicine(2021-2023)the Guangzhou High-level Clinical Key Specialty,the Guangzhou Research-oriented Hospital,the Innovative Clinical Technique of Guangzhou(2024-2026)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(grant number 2022A1515011567,2020A1515110565)the Guangzhou Science,Technology Planning Project(grant number 202201010714,202103000032)the National Natural Science Foundation of China(grant number 82471546)the Guangdong College Students Innovation and Entrepreneurship Training Project(grant number S202310570038)the Guangzhou Health Science and Technology Project(grant number 20231A010038)the Guangzhou Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Technology Project(grant number:20232A010013)the Science and Technology Plan Project of Guangzhou(2023A03J0842).
文摘Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression.Aim This study aimed to identify default mode network(DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression.Methods Data from a randomised controlled trial of iTBS in depression(n=82)were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN.Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment.Furthermore,the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated.Results Two distinct subgroups were identified.Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex,while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule.No main effect for subgroup,treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms.A significant subgroup×treatment interaction related to symbol coding improvement was detected(F=5.22,p=0.026).Within subgroup 1,the active group showed significantly greater improvement in symbol coding compared with the sham group(t=2.30,p=0.028),while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding(R2=0.35,RMSE(root-mean-square error)=5.72,p=0.013).Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions.
文摘Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mediated mainly by immunoglobulin E (IgE) in atopic individuals after exposure to allergens, with the typical symptoms of paroxysmal sneezing, watery runny nose, itchy nose and nasal congestion. Mendelian randomization (MR), an innovative epidemiological approach that uses common genetic variants as instrumental variables for exposure, thus enabling prediction of their causal relationship with outcomes, has been widely used in recent years in studies related to AR. This paper provides a review of the method and its progress in the field of allergic rhinitis research.
基金Supported by The Medical University of Warsaw,Poland
文摘AIM:To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation. METHODS:The MEDLINE,EMBASE,CINAHL,and Cochrane Library databases were searched in May 2009 for randomised controlled trials(RCTs)performed in paediatric or adult populations related to the study aim. RESULTS:We included five RCTs with a total of 377 subjects(194 in the experimental group and 183 in the control group).The participants were adults (three RCTs,n=266)and children(two RCTs,n= 111)with constipation.In adults,data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010,Lactobacillus casei Shirota,and Escherichia coli Nissle 1917 on defecation frequency and stool consistency.In children,L.casei rhamnosusLcr35,but not L.rhamnosus GG,showed a beneficial effect. CONCLUSION:Until more data are available,we believe the use of probiotics for the treatment of constipation condition should be considered investigational.
文摘Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional practice of fasting patients until the resumption of bowel function threatens to further contribute to the malnutrition experienced by these patients.Furthermore,the rationale behind this traditional practice has been rendered obsolete through developments in anaesthetic agents and changes to postoperative analgesia practices.Conversely,there is a growing body of literature that consistently demonstrates that providing oral or tube feeding proximal to the anastomosis within 24 h postoperatively,is not only safe,but might be associated with significant benefits to the postoperative course.Early post operative feeding should therefore be adopted as a standard of care in oncology patients undergoing gastrointestinal resections.
文摘Surgical resection remains the mainstay of treatment for gastric cancer.Laparoscopic assisted gastrectomy has failed to gain universal acceptance as an alternative to the open approach for a number of reasons,one of which includes the issue of oncological radicality in terms of lymph node dissection.Nodal status,which is one of the most crucial and independent predictors of patient survival,therefore has been examined both in single institutional trials and also in randomised controlled trials especially on early gastric cancer.The issue of oncological adequacy for laparoscopic lymph node harvesting for advanced gastric cancer remains a contentious issue because of the unique challenges it poses in terms of complexity,safety and time,and also the lack of randomised controlled trials in this area.It is thus imperative that good quality multicentre randomised controlled trials are designed to investigate the benef its of extended lymphadenectomy in the setting of laparoscopic surgery,especially for advanced gastric cancer and its impact on both short and long term survival.
文摘AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necessitate 6 wk wrist immobilisation.METHODS A prospective,randomised controlled single-centre trial was conducted with 56 patients who had a displaced radius fracture were randomised to treatment either with a volar locking plate(n=29),or another treatment modality(n=27;cast immobilisation with or without wires or external fixator).Outcomes were measured at 12 wk.Functional outcome scores measured were the Patient-Rated Wrist Evaluation(PRWE)Score;Disabilities of the Arm,Shoulder and Hand and activities of daily living(ADLs).Clinical outcomes were wrist range of motion and grip strength.Radiographic parameters were volar inclination and ulnar variance.RESULTS Patients in the volar locking plate group had significantly better PRWE scores,ADL scores,grip strength and range of extension at three months compared with the control group.All radiological parameters were significantly better in the volar locking plate group at 3 mo.CONCLUSION The present study suggests that volar locking plates produced significantly better functional and clinical outcomes at 3 mo compared with other treatment modalities.Anatomical reduction was significantly more likely to be preserved in the plating group.Level of evidence:Ⅱ.
文摘AIM To compare high definition white light endoscopy and bright narrow band imaging for colon polyps' detection rates. METHODS Patients were randomised to high definition white light endoscopy(HD-WLE) or the bright narrow band imaging(b NBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using b NBI with dual focus(b NBI-DF) according to the Sano's classification. The primary outcome was to compare adenoma detection rates(ADRs) between the two arms. The secondary outcome was to assess the negative predictive value(NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions.RESULTS A total of 1006 patients were randomised to HD-WLE(n = 511) or b NBI(n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in b NBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time(OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of b NBI was associated with a reduced ADR(OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps(86%) in both arms were predicted with high confidence. The sensitivity(Sn), specificity(Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using b NBI-DF for diminutive rectal polyps was 91.0%.CONCLUSION ADRs did not differ between b NBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. b NBI surpassed the PIVI threshold for diminutive polyps.
基金supported by the University of Macao(SRG2014-00019-FHSMYRG2015-00230 FHS+4 种基金MYRG2016-00005-FHS)the Affiliated Brain Hospital of Guangzhou Medical University(2016YFC0906302816713342014Y2-001052015BAI13B02)
文摘Background Hyperprolactinaemia is a common adverse effect of antipsychotics （APs）. The results of Peony-Glycyrrhiza decoction （PGD） as a potentially useful adjunctivetreatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials （RCTs） examined the effcacy and safety of adjunctive PGDtherapy for AP-induced hyperprolactinaemia.Methods English （PubMed, Embase, Cochrane Library, PsycINFO） and Chinese （Chinese National Knowledge Infrastructure, Wanfang Data） databases were systematicallysearched up to 10 June 2018. The inclusion criteria were based on PICOS-Participants： adult patients with schizophrenia; Intervention： PGD plus APs; Comparison： APs plus placebo or AP monotherapy; Outcomes： effcacy and safety; Study design： RCTs. The weighted mean difference （WMD） and risk ratio （RR） along with their 95% CIs were calculated using Review Manager （RevMan） V.5.3 software.Results Five RCTs （n=450） were included and analysed. Two RCTs （n=140） were double-blind and four RCTs （n=409） reported ‘random’ assignment with specifc description. The PGD group showed a signifcantly lower serum prolactin level at endpoint than the control group （n=380, WMD： ？32.69 ng/mL （95% CI -41.66 to 23.72）, p〈0.00001, I2=97%）. Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale （n=403, WMD： -0.62 （95% CI -2.38 to 1.15）, p=0.49, I^2=0%）. There were similar rates of all-cause discontinuation （n=330, RR 0.93 （95% CI 0.63 to 1.37）, p=0.71, I^2=0%） and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low’ （14.3%）, ‘low’ （42.8%）, ‘moderate’ （14.3%）, to ‘high’ （28.6%）.Conclusions Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactin-induced symptoms without signifcant adverse events in adult patients with AP-induced hyperprolactinaemia. High-quality RCTs with longer duration are needed to confrm these fndings.
文摘Objective: To report our experience of attempting a randomised controlled trial of an intensive lifestyle intervention for early type 2 diabetes delivered in a residential setting. Methods: We established a trial requiring 84 participants (46 standard care and 38 intervention) to detect a 1% difference in HbA1c between intervention and control groups at 12 months, allowing for attrition. Ethics approval was obtained from Monash University. Results: The study was abandoned after five months of consistent promotion due to recruitment failure (four subjects recruited). Conclusion: It appears to be difficult for patients with diabetes to commit to a live-in period of education regarding lifestyle modification as a means of treating the illness. We recommend better education of patients and their doctors about the potential health benefits of lifestyle change to manage type 2 diabetes, and further research into novel methods of delivering lifestyle advice which are both effective and sustainable.
文摘The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years.Their role appeared clear at the start of this century.The Helsinki Heart Study and Veterans Affairs High-Density Cholesterol Intervention Trial suggested significant benefit,especially in patients with atherogenic dyslipidaemia.However,this clarity disintegrated following the negative outcomes reported by the Bezafibrate Infarction Prevention,Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes randomised controlled trials.In this review we discuss these and other relevant trials and consider patient subgroups such as those with the metabolic syndrome and those needing treatment to prevent the microvascular complications associated with diabetes in whom fibrates may be useful.We also discuss observations from our group that may provide some explanation for the varying outcomes reported in large trials.The actions of fibrates in patients who are also on statins are interesting and appear to differ from those in patients not on statins.Understanding this is key as statins are the primary lipid lowering agents and likely to occupy that position for the foreseeable future.We also present other features of fibrate treatment we have observed in our clinical practice;changes in creatinine,liver function tests and the paradoxical high density lipoprotein reduction.Our purpose is to provide enough data for the reader to make objective decisions in their own clinical practice regarding fibrate use.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202006)Gansu Cheezheng Tibetan Medicine(BUCM-2021-JS-FW-087,Beijing,China).
文摘Objective:To evaluate the efficacy and safety of Baimai ointment in patients with lumbar disc herniation(LDH).Methods:This study presents a prospective randomized,double-blind,placebo-controlled,multicenter clinical trial protocol.A total of 194 cases will be employed,with a 1:1 allocation ratio for each group.Patients will receive either Baimai ointment or placebo over a 14-day treatment period,which will be followed by a 1-week follow-up period.Visual analogue scale scores will be used for the level of pain,the Japanese Orthopedic Association score will be measured primarily to determine the functional status,the Likert scale will be graded for the level of numbness,and rescue therapy use and compliance with health education will be recorded.Laboratory tests and adverse event records will also be applied for safety assessments.Discussion:In summary,this trial will assess the clinical efficacy and safety of Baimai ointment for LDH for the first time.The use of a placebo has the advantage of precluding anticipatory biases resulting from inadequate blinding.Outcome assessors,data managers,statisticians,and all related study staff will be blinded to avoid any bias caused by subjective factors in the study subjects and investigators.Valuable information for clinical LDH treatment and future research on Baimai ointment will be generated from the findings.
