Unplanned intensive care admission leading to an adverse event:Incidence,preventability and feature analysis

Objective:To compare the characteristics of patients between adverse event(AE)group and non-AE group,and to assess the causes,preventability,and severity of AE.Methods:A retrospective triple-phase medical record study was conducted at a Spanish tertiary hospital.Data was collected over a 6-month period,including all patients with an unplanned intensive care admission.Demographic characteristics,APACHE栻,length of ICU stay,mortality were compare between AE and non-AE group causes,preventability and severity were analyzed in AE cases.Results:597 Patients were included in the study.The overall incidence of AEs was 17.3%(n=103),of which 83.5%were considered preventable.Mortality within the AE group was higher than in the non-AE group(23.3%vs.13.6%),making it 1.7 times more frequent in the AE group(95%CI:1.143-2.071).The primary cause of AE was associated with surgical procedures(43.7%).Of the AEs,18.4%were classified as mild,58.3%as moderate,and 23.3%as severe.Conclusions:The incidence of unplanned intensive care admissions due to AE is high and potentially preventable.This is concerning given the high mortality observed in patients admitted to the intensive care unit because of an AE,although direct causality cannot always be established.The findings emphasize the importance of patient safety and underscore the need for improved quality and management of care resources.They also indicate where efforts should be directed to enhance care risk management.

Adverse Effects and Intervention of Frailty on Elderly Cancer Patients

Purpose:To study the adverse effects of frailty on elderly cancer patients and explore effective interventions.Methods:The convenience sampling method was used to select 362 elderly cancer patients who were consecutively admitted to the Oncology Department of the Affiliated Hospital of Hebei University from April 2020 to March 2021.The patients had five physical dimensions of activity tested and were divided into a frail group(n=128)and a non-frail group(n=234)based on the test results.The Chinese version of the Vulnerable Elders Questionnaire was formed on the basis of the Vulnerable Elders Survey-13(VES-13).The two groups of patients were surveyed within three days of admission.The questionnaire includes general information(age,gender,education level,marital status,monthly income,living area,smoking,and alcohol history,hearing,vision,and sleep status),Geriatric Depression Scale(GDS),Mini Nutritional Assessment(MNA),Mini-Mental State Examination(MMSE),and Charlson Comorbidity Index(CCI).Results:(1)By comparing the general information of the two groups of patients,it was found that the gender,education level,marital status,living area,and history of tobacco and alcohol had no statistical significance(P>0.05).In contrast,the frail group’s age,hearing status,vision status,and sleep status are significantly worse than those of the non-frail group(P<0.05);(2)Analysis of Vulnerable Elderly Questionnaire results found that the GDS scores in the frail group were higher than those in the non-frail group,and the MNA and MMSE scores were lower than those in the non-frail group(P<0.05).This indicated that the patients in the frail group had more severe depression,poor nutritional status,and specific impairments in cognitive function.Conclusion:Frailty adversely affects elderly cancer patients,and effective measures should be taken to intervene.

Advances in the study of waterlogging tolerance in plants

Waterlogging is one of the major abiotic stresses threatening crop yields globally.Under waterlogging stress,plants suffer from oxidative stress,heavy metal toxicity and energy deficiency,leading to metabolic disorders and growth inhibition.On the other hand,plants have evolved waterlogging-tolerance or adaptive mechanisms,including morphological changes,alternation of respiratory pathways,antioxidant protection and endogenous hormonal regulation.In this review,recent advances in studies on the effects of waterlogging stress and the mechanisms of waterlogging tolerance in plants are presented,and the genetic differences in waterlogging tolerance among plant species or genotypes within a species are illustrated.We also summarize the identified QTLs and key genes associated with waterlogging tolerance.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

Hemolysis attributed to high dose vitamin C:Two case reports

BACKGROUND High-dose vitamin C treatment(HVCT)can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy,which has been considered one of the safest alternative treatments.However,the severity of its adverse effects may have been underestimated.The most serious adverse effect is hemolysis,which may result in acute kidney injury or death.Although glucose-6-phosphate dehydrogenase(G6PD)deficiency is considered to be the main cause,the probability and pathological mechanism are not completely understood,leading to a lack of effective and standardized treatment methods.CASE SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT.In contrast to previous cases,the lowest hemoglobin level in the two cases was<50 g/L,which was lower than previously reported.This may be because Case 1 had chronic hepatitis B for many years,which caused abnormal liver reserve function,and Case 2 had grade II bone marrow suppression.Both patients improved and were discharged after blood replacement therapy.Our cases had the most severe degree of hemolysis but the best prognosis,suggesting that our treatment may be helpful for rescue of drug-induced hemolysis.This is the first review of the literature on hemolysis caused by HVCT,and we found that all patients with G6PD deficiency developed hemolysis after HVCT.CONCLUSION G6PD deficiency should be considered as a contraindication to HVCT,and it is not recommended for patients with bone marrow suppression,moderate-tosevere anemia,hematopoietic abnormalities,or abnormal liver and kidney function.Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Ophthalmic complications of injectable facial fillers

The recently published mini-review article by Miotti et al is an effort to clarify various aspects regarding the choice between fat grafts and fillers in facial aesthetic surgery.One of the complications associated with the administration of fillers is the possibility of vascular injury and spread of the dermal filler into the orbit,causing unexpected effects at a site distant from that of the initial injection,including ophthalmoplegia,ptosis and even visual compromise.Acute vision loss following filler injection is a devastating complication,occurring in up to 0.0008%of cases.The greatest risk of this complication occurs with nasal augmentation,followed by glabellar wrinkle treatment.While injected autologous fat predominantly occludes the proximal portion of the ophthalmic artery,hyaluronic acid fillers obstruct the ophthalmic artery comparatively distally.Treatment interventions include thrombolysis,hyperbaric oxygen therapy,oral aspirin,cobamamide and acetazolamide and administration of corticosteroids.However,most studies show a poor prognosis in the form of partial or no recovery of vision.Hence,prevention is of paramount importance.A high index of suspicion is also warranted on the part of both those administering as well as receiving injections of facial fillers to prevent potentially vision-threatening complications of this seemingly innocuous procedure.

Application of dezocine patient-controlled epidural analgesia in postoperative analgesia in patients with total myomectomy

BACKGROUND Uterine fibroids are common benign gynecological conditions.Patients who experience excessive menstruation,anemia,and pressure symptoms should be administered medication,and severe cases require a total hysterectomy.This procedure is invasive and causes severe postoperative pain,which can affect the patient’s postoperative sleep quality and,thus,the recovery process.AIM To evaluate use of dezocine in patient-controlled epidural analgesia(PCEA)for postoperative pain management in patients undergoing total myomectomy.METHODS We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups:A control group receiving 0.2%ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2%ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA.Outcomes assessed included pain levels,sedation,recovery indices,PCEA usage,stress factors,and sleep quality.RESULTS The observation group showed lower visual analog scale scores,shorter postoperative recovery indices,fewer mean PCEA compressions,lower cortisol and blood glucose levels,and better polysomnographic parameters compared to the control group(P<0.05).The cumulative incidence of adverse reactions was lower in the observation group than in the control group(P<0.05).CONCLUSION Dezocine PCEA can effectively control the pain associated with total myomectomy,reduce the negative impact of stress factors,and have less impact on patients’sleep,consequently resulting in fewer adverse effects.

Safety of teplizumab in patients with high-risk for diabetes mellitus type 1:A systematic review

BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.

Double-Blind, Parallel Group Study to Compare the Clinical Effectiveness of Calcium Dobesilate 500 mg BID vs. Calcium Dobesilate LP 1 g OD, in Patients with Chronic Venous Insufficiency of the Lower Limbs

Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with older age, smoking, lower extremity trauma, presence of an arteriovenous shunt, and elevated estrogen levels. All patients should be initially treated with conservative management. Venoactive drugs like calcium dobesilate are useful. Objectives: The primary objective compared the clinical improvement in patients with CVI, grades 0 - 3 of the CEAP classification of chronic venous disease, produced by two formulations of calcium dobesilate: calcium dobesilate LP 1 g OD vs calcium dobesilate 500 mg BID, immediate release. The secondary objective assessed the side effects of both formulations. Method: All patients took one tablet and one capsule at 7 am, and one capsule at 7 pm, for 8 weeks. One group received dobesilate 1 g OD and the other group received dobesilate 500 md BID. They were evaluated after 15, 30 and 60 days of treatment, using the symptom evaluation scale. Results: In both groups, there was a significant decrease in the symptom score after 15 days. Four patients in the Dobesilate OD group: had adverse effects, which did not require suspension of treatment. In the BID dobesilate group, there was one therapeutic failure, and one case of gastric discomfort. Conclusions: Prolonged-release Calcium dobesilate 1 g OD is as effective as calcium dobesilate 500 mg BID for the treatment of patients with chronic venous insufficiency.

Appropriateness of Amikacin Dose Prescription, Monitoring and Safety during Hospitalization as an Impact of Clinical Pharmacologist Intervention, in the Israeli Regional Hospital

Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.

Adverse effects of oral antiviral therapy in chronic hepatitis B

Oral nucleoside/nucleotide analogues(NAs) are currently the backbone of chronic hepatitis B(CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects(i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a "Black Box" warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus(HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.

Intravesical bacillus Calmette-Guerin(BCG)in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG(Danish 1331 and Moscow-I)

Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.

No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19

BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),raising a promising hypothesis that DPP4 inhibitor(DPP4i)drugs might be an optimal strategy for treating coronavirus disease 2019(COVID-19)among patients with diabetes.However,there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.METHODS We conducted a multicenter,retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province,China.After excluding ineligible individuals,142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis.We performed a strict propensity score matching(PSM)analysis where age,sex,comorbidities,number of oral hypoglycemic agents,heart rate,blood pressure,pulse oxygen saturation(SpO2)<95%,CT diagnosed bilateral lung lesions,laboratory indicators,and proportion of insulin usage were matched.Finally,111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users.Then,a linear logistic model and mixed-effect Cox model were applied to analyze the associations between inhospital DPP4i use and adverse outcomes of COVID-19.RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model,we found that there was no significant association between in-hospital DPP4i use(DPP4i group)and 28-d allcause mortality(adjusted hazard ratio=0.44,95%CI:0.09-2.11,P=0.31).Likewise,the incidences and risks of secondary outcomes,including septic shock,acute respiratory distress syndrome,or acute organ(kidney,liver,and cardiac)injuries,were also comparable between the DPP4i and non-DPP4i groups.The performance of DPP4i agents in achieving glucose control(e.g.,the median level of fasting blood glucose and random blood glucose)and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups.Furthermore,we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort.CONCLUSION Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment.The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.

Nursing of adverse effects in patients treated with liver resection plus sorafenib for hepatocellular carcinoma:5 cases report

There were very few reports of adverse effects in patients treated by liver resection in combination with sorafenib. We present 5 cases of hepatocellular carcinoma treated with liver resection plus sorafenib, trying to observing the adverse effects and seeking the nursing options to the adverse effects. The 5 patients were all males, and the mean age was （38.6-a：13.4） years. Tumor sizes were （6.7＋2.2） cm, and liver function was Child-Pugh class A. Diagnosis of Hepatocellular carcinoma （HCC） was confwmed by postoperative pathology. During the follow-ups, all the 5 patients had different degrees of adverse effects, of which 5 patients had diarrhea, 3 had hand-foot skin reaction, 1 had hypertension and 1 had alopecie. Diarrhea seems common in these patients, and it appeared early after treatment. For those patients with adverse effects, management measures were given immediately, including nursing interventions and some medicines. Psychological and symptomatic nursing guidance can help patients overcome the adverse effects. No patients suffered dose reduction or treatment discontinuation.

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival

BACKGROUND Despite the popularity of immune checkpoint inhibitors(ICIs)in the treatment of advanced cancer,patients often develop gastrointestinal(GI)and non-GI immune-related adverse events(irAEs).The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports.This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment.AIM To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs.METHODS In this single-center,retrospective,observational study,we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020.We analyzed the clinical characteristics of patients who received ICI treatment.We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer(LC)and malignant melanoma(MM).Kaplan-Meier analysis was used to compare the median overall survival(OS).Multivariate Cox proportional hazards models were used to identify prognostic factors.A P value<0.05 was considered statistically significant.RESULTS GI-irAEs occurred in 34 of 605 patients(5.6%)treated with an anti-programmed cell death-1/programmed death-ligand 1(anti-PD-1/PD-L1)antibody alone and in nine of 56 patients(16.1%)treated with an anti-cytotoxic T-lymphocyte antigen 4(CTLA-4)antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies.The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies(P<0.05).In 130 patients with MM,OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs(P=0.035).In contrast,in 209 patients with non-small cell LC,there was no significant difference in OS between the groups.The multivariate analyses showed that a performance status of 2-3(hazard ratio:2.406;95%confidence interval:1.125–5.147;P=0.024)was an independent predictive factor for OS in patients with MM.CONCLUSION Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies.Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

Pain reduction and adverse effects of intravenous metoclopramide for acute migraine attack: A systematic review and meta-analysis of randomized-controlled trials

BACKGROUND Metoclopramide may be used to treat people suffering from acute migraine.However,no comprehensive investigation on this issue has been recorded.This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.AIM To compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department(ED).METHODS We included randomized controlled trials of participants older than 18 years with acute migraine headaches,which included at least one arm that received intravenous(IV)metoclopramide at the ED.A literature search of PubMed,Web of Science,Cochrane Collaboration,and Reference Citation Analysis on December 31,2021 retrieved other drugs or placebo-controlled studies without language limitation.The risk of bias was assessed using the Cochrane risk of bias tool.The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment,as measured by the pain scale.Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.RESULTS Fourteen trials with a total of 1661 individuals were eligible for review.The risk of bias ranged from low to intermediate.IV metoclopramide administration was not associated with higher pain reduction at 1 h(Standard mean difference[SMD]=-0.03,95%confidence interval[CI]:-0.33-0.28,P=0.87).However,metoclopramide was associated with better pain reduction than placebo(SMD=1.04,95%CI:0.50-1.58,P=0.0002).In addition,side effects were not significantly different between IV metoclopramide and other drugs or placebo(odds ratio[OR]=0.76,95%CI:0.48-1.19,P=0.09 and OR=0.92,95%CI:0.31-2.74,P=0.54,respectively).CONCLUSION Metoclopramide is more effective than placebo in treating migraine in the ED.Despite the observed tendency of decreased side effects,its effectiveness compared to other regimens is poorly understood.More research on this area is needed to treat migraine in acute care settings effectively.

Biomarkers for gastrointestinal adverse events related to thiopurine therapy

Thiopurines are immunomodulators used in the treatment of acute lymphoblastic leukemia and inflammatory bowel diseases.Adverse reactions to these agents are one of the main causes of treatment discontinuation or interruption.Myelosuppression is the most frequent adverse effect;however,approximately 5%-20%of patients develop gastrointestinal toxicity.The identification of biomarkers able to prevent and/or monitor these adverse reactions would be useful for clinicians for the proactive management of long-term thiopurine therapy.In this editorial,we discuss evidence supporting the use of PACSIN2,RAC1,and ITPA genes,in addition to TPMT and NUDT15,as possible biomarkers for thiopurine-related gastrointestinal toxicity.

Effectiveness and adverse effects of hormonal therapy for prostate cancer： Japanese experience and perspective

Recently, novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer. We believe that these new developments will improve hormonal therapy. On the other hand, there has been an increase in criticism of hormonal therapy, because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease. In this review, we have introduced the Japanese experience of hormonal therapy, because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy. First, we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought. Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer. Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy. We showed that the death from cardiovascular dis- eases in Japanese patients receiving hormonal therapy was not higher than that in the general population. However; efforts should be made to decrease the adverse effects of hormonal therapy, because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan. Managements of endocrine and metabolic dysfunction, such as diabetes mellitus, are essential. New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

Assessing Adverse Effects of Aroclor 1254 on Perinatally Exposed Rat Offspring

To assess the neurotoxic effects and redoxresponses of Aroclor 1254 （A1254） on perinatallyexposed rat offspring, A1254 was administered bygavage from gestational day （GD） 6 to postnatal day（PND） 21. Neurobehavioral development,antioxidant enzyme activities, lipid peroxidation（LPO）, nitric oxide （NO）, and NO synthase （NOS）levels were analyzed in the offspring.Neurobehavioral development analysis revealeddelayed appearance of the righting reflex, negativegeotaxis, and cliff drop test responses in A1254exposed group. Developmental A1254 exposurealso caused oxidative stress in the brain of PND 22offspring via reductions in the activity of SOD andGSH-Px, and by promoting a rise in the levels of NOand NOS.

Modeling and simulation of induction motor drive system to investigate and mitigate of PWM inverter’s adverse effects

Modeling and simulation of induction motor drive system to investigate and mitigate the adverse effects of PWM inverter based on analysis, modeling and simulation are presented. The estimation of conducted disturbances and other adverse effects of PWM inverter by simulation offer a considerable gain from the economic point of view. For an accurate model of the motor drive system including mains, rectifier, inverter, motor and its long cables, the high frequency parasitic current paths are taken into account. The novel model and its parasitic values for three-phase induction motor system are presented. Finally a new solution for suppressing EMI, common mode voltage, leakage current, bearing current and shaft voltages is proposed and the results show the excellent performances of proposed solution including active and passive filters.