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.

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.

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.

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.

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.

Systemic adverse effects and toxicities associated with immunotherapy:A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers.Immunotherapeutic agents have gained immense popularity due to their tumorspecific action.Immunotherapy is slowly transforming into a separate therapeutic entity,and the fifth pillar of management for cancers alongside surgery,radiotherapy,chemotherapy,and targeted therapy.However,like any therapeutic entity it has its own adverse effects.With the increasing use of immunotherapeutic agents,it is vital for physicians to acquaint themselves with these adverse effects.The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents.We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems,as well as an extensive discussion of the current recommendations for treatment and clinical trial data.As we continue to see increasing usage of these agents in clinical practice,it is vital for physicians to familiarize themselves with these effects.

Efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain

Objective The aim of the study was to investigate the efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain.Methods Forty patients with digestive system cancer were enrolled,who had moderate to severe refractory neuropathic pain;the patients were treated with olanzapine for 2 weeks at a daily dosage of 5 mg to 10 mg per night according to patients’response and tolerability,combined with conventional analgesic therapy.Pain intensity was evaluated by using a Numeral Rating Scale(NRS)at baseline,3 days,and 2 weeks after therapy.The Pittsburg Sleep Quality Index(PSQI)was evaluated at baseline and 2 weeks after therapy.Data on adverse events were recorded.The dosage of conventional analgesics was adjusted over time based on the severity of pain.Results The mean pain score decreased by 2.575±1.318(P<0.000)at 3 days and by 3.400±1.614(P<0.000)at 2 weeks;30%of the patients experienced significant pain relief at 3 days and 50%at 2 weeks.The PSQI decreased by 4.725±2.828(P<0.000)at 2 weeks.The adverse events induced by olanzapine included sleepiness,weight gain,dizziness,fatigue,dry mouth,and constipation;all the side effects were mild.Conclusion When combined with conventional analgesic therapy,olanzapine was effective in relieving pain and sleep disturbance,and was well-tolerated among patients with refractory neuropathic pain.

Blood and Histopathological Biomarkers of Immune-related Adverse Effects of Treatment with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

Adverse effects of exposure to fine particles and ultrafine particles in the environment on different organs of organisms

Particulate pollution is a global risk factor that seriously threatens human health.Fine particles(FPs)and ultrafine particles(UFPs)have small particle diameters and large specific surface areas,which can easily adsorb metals,microorganisms and other pollutants.FPs and UFPs can enter the human body in multiple ways and can be easily and quickly absorbed by the cells,tissues and organs.In the body,the particles can induce oxidative stress,inflammatory response and apoptosis,furthermore causing great adverse effects.Epidemiological studies mainly take the population as the research object to study the distribution of diseases and health conditions in a specific population and to focus on the identification of influencing factors.However,the mechanism by which a substance harms the health of organisms is mainly demonstrated through toxicological studies.Combining epidemiological studies with toxicological studies will provide a more systematic and comprehensive understanding of the impact of PM on the health of organisms.In this review,the sources,compositions,and morphologies of FPs and UFPs are briefly introduced in the first part.The effects and action mechanisms of exposure to FPs and UFPs on the heart,lungs,brain,liver,spleen,kidneys,pancreas,gastrointestinal tract,joints and reproductive system are systematically summarized.In addition,challenges are further pointed out at the end of the paper.This work provides useful theoretical guidance and a strong experimental foundation for investigating and preventing the adverse effects of FPs and UFPs on human health.

Pharmacological importance of Kunxian Capsule in clinical applications and its adverse effects:A review

Kunxian Capsule(KX)is a popular Chinese patent medicine for the treatment of rheumatoid arthritis,nephrotic syndrome,systemic lupus erythematosus,Henoch-Schönlein purpura,ankylosing spondylitis,psoriatic arthritis and eczema.However,there is scarcity of comprehensive information on the significance of KX in the clinical application and its side effects.Hence,it is aimed to provide a review of the significance of KX,with a focus on the pharmacological effects,clinical applications,and its adverse reactions.This review was based on the published literatures in PubMed,China National Knowledge Infrastructure and WanFang database.The articles were collected by two independent authors with no time limits applied until November 30,2022.The search term includes Kunxian Capsule and/or clinical effect,pharmacology,disease,therapy,adverse effects and quality control.KX has been shown to be effective in the treatment of autoimmune arthritis by inhibiting inflammatory responses and inducing apoptosis.Many studies suggest that KX has anti-inflammatory and analgesic properties that aid in the improvement of joint functions.KX dispels wind,removes dampness,invigorates the kidneys,and promotes blood circulation,thereby curing various diseases.However,studies also suggest KX-related adverse reactions in multiple systems.Overall,this review highlights the scientific basis of KX in curing or preventing various diseases and provides novel insights for further research and clinical applications.

A potentially serious adverse effect of GLP-1 receptor agonists

To the Editor:Glucagon-like peptide-1(GLP-1)is a small intestine-derived hormone^(1,2).Its peptidic analogs include exenatide,lixisenatide,dulaglutide,liraglutide,albiglutide,semaglutide,etc.They work as GLP-1 receptor agonists(GLP-1RAs)to treat type 2 diabetes,obesity,hypertension and dyslipidemia.Among them。

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.

Alpha-1-acid glycoprotein as potential predictive biomarker of docetaxel adverse effects in breast cancer patients

In the present study, we aimed at identifying the potential relationship between baseline alpha-l-acid glycoprotein （AAG） and the adverse effects of docetaxel in breast cancer patients. A total of 87 breast cancer patients receiving docetaxe 1 at a dose 75 mg/m2 once every 3 weeks as a single agent in adjuvant and neoadjuvant chemotherapy were enrolled in this study. Baseline AAG was determined at the day before usage of decetaxel in the first cycle. Febrile neutropenia, grade 3-4 stomatitis, grade 3-4 diarrhea and severe asthenia was determined as safety end points. Common Terminology Criteria of Adverse Effects （CTCAE） V4.0 was used to evaluated the adverse effects during the first cycle of chemotherapy. The mean age of patients was 47.7~8.89 years. Mean baseline AAG was 0.99~0.24 g/L. Primary adverse effects during the chemotherapy was febrile neutropenia （30%）, grade 3-4 stomatitis （17%）, grade 3-4 diarrhea （23%）, and severe asthenia （20%）. Among those adverse effects, febrile neutropenia, grade 3-4 stomatitis and grade 3-4 diarrhea had shown significant association with mean difference of baseline AAG （P〈0.01）. Patients who developed febrile neutropenia （n = 26） had lower baseline AAG level of 0.838±0.192 g/L compared with 1.051±0.236 g/L in patients who did not experience such effect （n = 61）. Also, the level of baseline AAG in patients who had grade 3-4 stomatitis （0.760±0.176 g/L） and grade 3-4 diarrhea 0.800±0.172 g/L） is lower than those who did not had these events. Baseline AAG is appears to be used as a predictive biomarker of adverse effects in breast cancer patients treated with docetaxel.

Sexual,physical and overall adverse effects in patients treated with 5a-reductase inhibitors:a systematic review and meta-analysis

Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors(5ARIs)increases the risk of PFS-like adverse effects.A search of studies published until May 10,2020,was performed using PubMed,EMBASE,and the Cochrane Library.We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia(BPH)or androgenetic alopecia(AGA),and identified 34 studies from 28 articles that met our eligibility criteria.In the random-effects model,the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial(95%confidence interval[CI]:1.64-2.14).Regarding specific types of adverse effects,the use of 5ARIs had a 1.89-fold risk of sexual adverse effects(95%CI:1.74-2.05)and was associated with an increased risk of physical adverse effects(relative risk[RR]:1.31,95%CI:0.80-2.15),albeit without statistical significance.This meta-analysis helped to better define the adverse effects caused by 5ARIs.We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment.Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity

Treatment of adolescents with antidepressants may induce an increased risk for suicidality in this population. The activity of the amygdala during processing of emotional faces with functional Magnetic Resonance Imaging （fMRI） is a well-known measure of emotional dysregulation. Based upon data of our prematurely ended randomized clinical trial with fluoxetine （NTR3103） in anxious and or depressed girls （12-14 years of age） we calculated that with the found effect size of r = 0.66, compared to placebo, only 8 subjects are heeded to demonstrate increased amygdala activity following 16 weeks of treatment with fluoxetine.

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.