Why Don’t We Adequately Identify and Manage Adverse Drug Reactions despite Having the Needed Information?

Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.

Allergen degradation of bee pollen by lactic acid bacteria fermentation and its alleviatory effects on allergic reactions in BALB/c mice

Food allergy as a global health problem threatens food industry.Bee pollen(BP)is a typical food with allergenic potentials,although it performs various nutritional/pharmacological functions to humans.In this study,lactic acid bacteria(LAB)were used to ferment Brassica napus BP for alleviating its allergenicity.Four novel allergens(glutaredoxin,oleosin-B2,catalase and lipase)were identified with significant decreases in LAB-fermented BP(FBP)than natural BP by proteomics.Meanwhile,metabolomics analysis showed significant increases of 28 characteristic oligopeptides and amino acids in FBP versus BP,indicating the degradation of LAB on allergens.Moreover,FBP showed alleviatory effects in BALB/c mice,which relieved pathological symptoms and lowered production of allergic mediators.Microbial high-throughput sequencing analysis showed that FBP could regulate gut microbiota and metabolism to strengthen immunity,which were closely correlated with the alleviation of allergic reactivity.These findings could contribute to the development and utilization of hypoallergenic BP products.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal.Additionally,ursodeoxycholic acid(UDCA)can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concen-tration in bile.Despite these treatment options,there are still patients who experience stone recurrence.The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People’s Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected.According to the post-ERCP treatment plan,100 patients were classified into UDCA(n=47)and control(n=53)groups.We aimed to assess the clinical efficacy and rate of relapse in the two patient populations.We then collected information(basic demographic data,clinical characteristics,and serum biochemical indicators)and determined the factors contributing to relapse using logistic regression analysis.Our secondary goal was to determine the effects of UDCA on liver function after ERCP.Compared to the control group,the UDCA group demonstrated a higher clinical effectiveness rate of 92.45%vs 78.72%(P<0.05).No significant differences were observed in liver function indices,including total bilirubin,direct bilirubin,gamma-glutamyl transpeptidase,alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase,between the two groups before treatment.After treatment,all liver function indices were significantly reduced.Comparing the control vs UDCA groups,the UDCA group exhibited significantly lower levels of all indices(55.39±6.53 vs 77.31±8.52,32.10±4.62 vs 45.39±5.69,142.32±14.21 vs 189.63±16.87,112.52±14.25 vs 149.36±15.36,122.61±16.00 vs 171.33±22.09,96.98±10.44 vs 121.35±11.57,respectively,all P<0.05).The stone recurrence rate was lower in the UDCA group(13.21%)in contrast with the control group(44.68%).Periampullary diverticula(OR:6.00,95%CI:1.69-21.30),maximum stone diameter(OR:1.69,95%CI:1.01-2.85),stone quantity>3(OR:4.23,95%CI:1.17-15.26),and positive bile culture(OR:7.61,95%CI:2.07-27.91)were independent factors that influenced the relapse of common bile duct stones after ERCP(P<0.05).Furthermore,postoperative UDCA was identified as a preventive factor(OR:0.07;95%CI:0.08-0.09).CONCLUSION The intervention effect of UDCA after ERCP for common bile duct stones is adequate,providing new research directions and references for the prevention and treatment of stone recurrence.

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.

Sequential Treatment Reduces the Acute Phases of Adverse Effect of Zoledronic Acid in First Time Users

Objective: To investigate whether sequential regimen such as traditional anti-reabsorption medications followed by zoledronic acid could reduce the side effects after initiation of zoledronic acid in postmenopausal osteoporosis patients. Methods: A total of 156 postmenopausal osteoporosis patients who presented at our osteoporosis outpatient clinic were enrolled in this study. They were randomly divided into four groups: the control group, alendronate group, calcitonin group, and raloxifene group. All participants were treated with Caltrate 600 mg per day and calcitriol 0.25 ug per day as a baseline treatment, followed by administrating 5 mg/100 mL of zoledronic acid intravenously for one single time three months afterwards. During the abovementioned course of three months, the alendronate group received 70 mg of alendronate sodium orally once a week, the calcitonin group received nasal spray form of salmon calcitonin 10iu daily, the raloxifene group received 60mg of raloxifene orally daily, and the control group received nothing but only the baseline treatment. We tested parameters such as β-cross, blood calcium level, renal function both pre and post zoledronic acid treatment. We also documented those side effects that typically occurred within one week of treatment initiation, which included the proportion, severity, onset time, and duration of the fever, demand for pain medication, severity of bone and joint pain, flu-like symptoms, arrhythmia, blood calcium level, and kidney function impairment. We also evaluated how willing the patients were to receive a second dose of zoledronic acid. Then we did comparative analysis between control group and sequential group. Results: The side effects such as fever, bone and joint pain, flu-like symptoms after zoledronic acid treatment in alendronate group and calcitonin group were all significantly lower than that in control group, while raloxifene group showed no significant difference compared to that in the control group. The proportions of patients who needed NSAIDs in the alendronate group and the calcitonin group were significantly lower than that in control group. However, the raloxifene group showed no significant difference in the NSAIDs demand from that of the control group. The percentages of patients who consented to a second dose of zoledronate therapy in the alendronate, calcitonin and raloxifene groups were significantly higher than that in the control group. Conclusions: Sequential treatment with alendronate sodium or calcitonin can significantly reduce the side effects such as fever, bone/joint pain, flu-like symptoms caused by first-time zoledronic acid therapy. Raloxifene sequential treatment does not seem to have decreased or increased the side effects of zoledronic acid treatment. Also, sequential treatment can improve the patient compliance with a second dose of zoledronic acid.

Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis.

Induced Effects of Exogenous Phenolic Acids on Allelopathy of a Wild Rice Accession(Oryza longistaminata,S37)

Four exogenous phenolic acids, including salicylic acid, fumalic acid, p-coumaric acid and p-hydroxybenzonic acid, were used to investigate the regulatory effects on allelopathy of a wild rice accession of S37 （Oryza Iongistaminata）, which is a known allelopathic rice. The four exogenous phenolic acids induced the enhancement of the allelopathic potential of wild rice S37 in target weeds though the weed-suppressive activities were low, and the inducible effects were dependent on the specific phenolic acid, concentration and treatment time. After foliar application of exogenous phenolic acids, the inhibition rates for plant height, root length and fresh weight of barnyard grass （Echinochioa crus-galli） were significantly higher than those of the control. Especially at the concentration of 100 mg/L, the inhibition rates for plant height and fresh weight of barnyard grass by fumalic acid were 38.12% and 26.31% higher than those of the control, showing that fumalic acid was more effective compared with other phenolic acids in inhibiting monocotyledon weed growth. Furthermore, the weedsuppressive activity of aqueous extract from the leaves of wild rice S37 treated with exogenous phenolic acids was increased, and it peaked at 48 h after the treatment with the aqueous extract, and then gradually declined.

Leaching Effect of Organic Acids on Heavy Metal Contaminated Soil

With the contamination of soil heavy metals becoming more and more serious,remediation has become a hot issue,and it is of great significance to study the remediation effects of heavy metal contaminated soil. The heavy metal contaminated soil was leached with water,acetic acid and citric acid,and the pH value of the soil after leaching was adjusted with 2% lime water. Finally,the pH value and conductivity of the soil leacheate were determined. The results showed that the best leacheate was citric acid for the remediation of soil contaminated with heavy metals Cu,Cd and Pb,and the optimum leaching concentration was 1. 0,0. 4,0. 7 mol/L,respectively. For the remediation of soil contaminated with Zn,the best leacheate was acetic acid,and the optimal leaching concentration was 1 mol/L. The leaching effect of lime water on heavy metal contaminated soil was positively correlated with the concentration of organic acid,that is,the leaching effect on heavy metals was better at stronger acidic condition. The conductivity of the soil sample treated with lime water increased with the increase of the concentration of organic acid,and at the same concentration,the conductivity was in the order of citric acid > acetic acid.

Efficacy of Folinic Acid in Comparison to Folic Acid for Reducing Side Effects of Methotrexate in Children with Juvenile Idiopathic Arthritis

Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Perfluorooctanoic acid(PFOA)is a widespread synthetic persistent organic pollutant that may enrich along the food chain and affect the growth,development,reproduction,and lipid metabolism of aquatic organisms,particularly the benthic organisms.How-ever,the toxic effects of PFOA on the half-smooth tongue sole Cynoglossus semilaevis,a commercial benthic fish in China,have rarely been reported.Because juvenile fish are sensitive to environmental pollutants,in the present study,histological assessment and tran-scriptome sequencing were performed to determine the short-term impact of PFOA on juvenile half-smooth tongue soles.Histologi-cal analysis showed that PFOA exposure caused hepatocyte rupture,intestinal villi breakage,increased goblet cell count,and brain ab-normal.Transcriptome results showed that some interesting signaling pathways,such as glycolysis/gluconeogenesis,PPAR signaling pathway and GABAergic synapse signaling pathway,were enriched after PFOA exposure.In addition,some metabolic,immune and neural genes were differentially expressed,which including ependymin,hbb1-like and gad 1,and they were up-regulated after 14 days of exposure.Transcriptome results also indicated that half-smooth tongue sole might improve energy metabolism in response to PFOA toxicity after 7 days of exposure.These findings provide a basis for studying the ecological effects of PFOA on marine benthic fishes.

A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle

Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids(FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study(GWAS) on milk FAs in dairy cattle, 83 genomewide significant single nucleotide polymorphisms(SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18 index(P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3000 bp of 5′ and 3′ regulatory regions of the AGPA T3 gene, a total of 17 SNPs were identified, including four in 5′ regulatory region, one in 5′ untranslated region(UTR),three in introns, one in 3′ UTR, and eight in 3′ regulatory region. By the linkage disequilibrium(LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs,respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0(P < 0.0001–0.0384). Further, with Genomatix, we predicted that four SNPs in 5′ regulatory region(g.146702957 G > A, g.146704373 A > G, g.146704618 A > G and g.146704699 G > A) changed the transcription factor binding sites(TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373 A > G and g.146704618 A > G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G(P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.

Effect of Octadecadienoic Acid on Proliferation and Apoptosis of Glioma Cells and Its Mechanism

[Objectives] To explore the inhibitory effect of octadecadienoic acid (ODA) on proliferation and apoptosis of glioma cells and its mechanism. [Methods] Cultured human glioma cells (cell density 2×10^(6) cells/L) were divided into three groups: solvent control group (DMSO, 30 μL/L), 5-FU group (10 mg/L) and octadecadienoic acid group (0.3, 0.6, 1.2 mg/L). The toxic effects of ODA on glioma cells were detected by trypan blue and thiazolium blue (MTT). The expression of P53, PI3K, P21, PKB/Akt and caspase-9 protein in glioma cells were detected by enzyme-linked immunosorbent assay (ELISA). [Results] The cell count under optical microscope showed that the inhibition rate of cell proliferation in low, medium and high dose ODA groups and 5-FU group was significantly higher than that in solvent control group ( P <0.01), but there was no significant difference compared with 5-FU group ( P >0.05). The results of MTT showed that compared with the solvent control group, the inhibition rate of cell proliferation in low, medium and high dose ODA groups and 5-FU group significantly increased ( P <0.01);compared with 5-FU group, the inhibition rate of cell proliferation in high dose ODA group significantly increased ( P <0.01). The results of flow cytometry showed that compared with the solvent control group, the number of cells in G_(0)/G_(1) phase increased significantly ( P <0.05, P <0.01), the number of cells in G_(2)/M phase decreased significantly ( P <0.01) and the apoptosis rate increased significantly ( P <0.01) in the low, medium and high dose ODA groups and 5-FU group;compared with 5-FU group, the number of cells in G_(2)/M phase decreased significantly ( P <0.01) and the apoptosis rate increased significantly ( P <0.01) in ODA group. ELISA testing results showed that the expression levels of P53, P13K and PKB/Akt in low, medium and high dose ODA groups and 5-FU group were significantly lower than those in solvent control group ( P <0.01), and only the expression level of protein in high dose ODA group was significantly lower than that in 5-FU group ( P <0.01);the expression levels of P21 and caspase-9 in low, medium and high dose ODA groups and 5-FU group were significantly higher than those in solvent control group ( P <0.05, P <0.01), but the expression level of protein in high dose ODA group was significantly higher than that in 5-FU group ( P <0.01). [Conclusions] ODA can obviously inhibit the proliferation of glioma cells and induce apoptosis. The mechanism is related to up-regulation of P21, caspase-9, down-regulation of P53, PI3K, PKB/Akt, inhibition of cell division cycle and decrease of PI3K-Akt signal transduction pathway.

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.

Adverse Effects of Inactivated Foot-and-Mouth Disease Vaccine—Possible Causes Analysis and Countermeasures

Foot-and-mouth disease (FMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, and Chinese government adopts compulsory immunization measures for FMD. The adverse effects of FMD vaccine to pigs, cattle and goats have been reported increasingly frequent during the spring and autumn seasons when large numbers of farm livestock are vaccinated. The financial losses caused by vaccine adverse effects have been a serious concern for both farmers and primary prevention personnel. There are various causative factors reported to involve into adverse effect of FMD vaccine, including the inappropriate vaccine production, transportation and storage, livestock poor tolerance, and unqualified vaccinating manipulations. Symptomatic treatment and early drug prevention have a certain effect on the adverse effects. To analyze causes and propose countermeasures, in the current study possible reasons during the production and processing procedures of inactivated FMD vaccine were reviewed and corresponding countermeasures were recommended. The review may provide references for better use of vaccine to prevent FMD.

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.

Hypertrophic Scar Formation and Wound Healing Modulation Fatty Acids as Modulators of Severe Scars

Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.

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.

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±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 confirmed 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.

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.

Study on thermal decomposition kinetics of azobenzene-4,4′-dicarboxylic acid by using compensation parameter method and nonlinear fitting evaluation

Recently,azobenzene-4,4'-dicarboxylic acid(ADCA)has been produced gradually for use as an organic synthesis or pharmaceutical intermediate due to its eminent performance.With large quantities put into application in the future,the thermal stability of this substance during storage,transportation,and use will become quite important.Thus,in this work,the thermal decomposition behavior,thermal decomposition kinetics,and thermal hazard of ADCA were investigated.Experiments were conducted by using a SENSYS evo DSC device.A combination of differential iso-conversion method,compensation parameter method,and nonlinear fitting evaluation were also used to analyze thermal kinetics and mechanism of ADCA decomposition.The results show that when conversion rate α increases,the activation energies of ADCA's first and main decomposition peaks fall.The amount of heat released during decomposition varies between 182.46 and 231.16 J·g^(-1).The proposed kinetic equation is based on the Avrami-Erofeev model,which is consistent with the decomposition progress.Applying the Frank-Kamenetskii model,a calculated self-accelerating decomposition temperature of 287.0℃is obtained.