Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
Objective:To investigate the pattern of antibiotic resistance and biofilm production capabilities of clinical Acinetobacter baumannii(A.baumannii)isolates in this study.Methods:A.baumannii isolates were collected from...Objective:To investigate the pattern of antibiotic resistance and biofilm production capabilities of clinical Acinetobacter baumannii(A.baumannii)isolates in this study.Methods:A.baumannii isolates were collected from Tehran Imam Khomeini Hospital in this cross-sectional study,and the minimum inhibitory concentrations for 16 antibiotics were determined using Vitek2®systems.All isolates were analyzed for biofilm production,then presence of biofilm-associated genes,and class Ⅰ and Ⅱ integron genes.Results:60 non-replicate A.baumannii isolates were included in this study.The resistance rates reached 100%for aztreonam,cefepime,ceftazidime,ciprofloxacin,piperacillin-tazobactam,piperacillin,ticarcillin,and trimethoprim-sulfamethoxazole.A.baumannii isolates were most sensitive to colistin and rifampicin being the most effective treatments.Multi-drug resistant and extensively drug-resistant isolates accounted for 83.3%and 16.7%,respectively.Of the isolates,91.6%formed biofilms,categorized as 10%strong,31.6%moderate,and 50%weak.No correlation was found between antibiotic resistance and biofilm formation.The genes csuE,abaI,and ompA were prevalent,but their distribution was similar across biofilm categories.A relationship between Int1 and biofilm production was noted.Conclusions:The high rates of antibiotic resistance and biofilm formation,alongside the presence of integrons including class Ⅰ and Ⅱ,underscore the necessity for ongoing monitoring of A.baumannii.Notably,classⅠintegron presence was significantly linked to biofilm formation.Further research is needed to explore the connection between antibiotic resistance and biofilm production in A.baumannii.展开更多
Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out...Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.展开更多
In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and quali...In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and qualitative data,is grounded in preferences regarding disability status.This review delineates the algorithm used to calculate the value of the proposed DALY synthetic indicator and elucidates key methodological challenges associated with its application.In contrast to the quality-adjusted life years approach,derived from multi-attribute utility theory,the DALY stands as an independent synthetic indicator that adopts the assumptions of the Time Trade Off utility technique to define Disability Weights.Claiming to rely on no mathematical or economic theory,DALY users appear to have exempted themselves from verifying whether this indicator meets the classical properties required of all indicators,notably content validity,reliability,specificity,and sensitivity.The DALY concept emerged primarily to facilitate comparisons of the health impacts of various diseases globally within the framework of the Global Burden of Disease initiative,leading to numerous publications in international literature.Despite widespread adoption,the DALY synthetic indicator has prompted significant methodological concerns since its inception,manifesting in inconsistent and non-reproducible results.Given the substantial diffusion of the DALY indicator and its critical role in health impact assessments,a reassessment is warranted.This reconsideration is imperative for enhancing the robustness and reliability of public health decisionmaking processes.展开更多
Introduction:The occurrence of congenital anomalies is one of the serious challenges in the world.Therefore,identifying related factors to reduce it is of particular importance.This study aimed to determine the incide...Introduction:The occurrence of congenital anomalies is one of the serious challenges in the world.Therefore,identifying related factors to reduce it is of particular importance.This study aimed to determine the incidence and factors related to congenital anomalies.Methods:An epidemiology study was conducted on 1567 infants and their parents in Kermanshah,Iran.The required information was extracted from the ffles of mothers in health centers.The data collection tool was a researcher-made checklist of 39 questions.The data was statistically analyzed with the STATA version 14 software.Result:The incidence of congenital anomalies was 2.9%(n=45).Brain anomalies(n=10)and pulmonary anomalies(n=8)were the most common congenital anomalies in newborns.The results showed that parents’age(p=0.001),place of residence(p=0.022),mother’s occupation(p=0.010),hemoglobin level(p=0.002),blood pressure disorders(p=0.001),bleeding during pregnancy(p=0.001),infection during pregnancy(p=0.001),multivitamins(p=0.002)and women’s previous birth records such as previous abnormal birth history(p=0.015),abortion history(p=0.001),stillbirth history(p=0.001),birth history of infant less than 2500 g(p=0.001)was found to have a statistically signiffcant relationship with congenital anomalies.Conclusion:The incidence of congenital anomalies was high in Kermanshah city.Considering the identiffcation of risk factors and preventive factors related to congenital anomalies,it is suggested that interventions be carried out in health centers to increase awareness among pregnant women to reduce the incidence of anomalies.展开更多
Objective:To explain barriers to childbearing among working women from the perspective of working women and midwives.Methods:In this study,a qualitative study of content analysis method was employed.The study was cond...Objective:To explain barriers to childbearing among working women from the perspective of working women and midwives.Methods:In this study,a qualitative study of content analysis method was employed.The study was conducted from December 2021 to July 2022.The population consisted of working women and midwives.Data collection was conducted using semi-structured interviews and continued until data saturation was achieved.Through purposeful sampling,10 women and 11 midwives were selected as the sample.The data were analyzed by Graneheim and Lundman content analysis approach.For more rigorous,Nvivo 14 software was also used for data management,analysis,coding and organization of data.Results:This study included 21 women(10 women employees and 11 midwives)aged 25-43 years(for women employees)and 27-56 years(for midwives)with 1 to 34 years of job experience.In examination of participant’views about the barriers to childbearing,1124 codes were identified,of which we managed to extract six subthemes and two themes.Two themes emerged:“lack of social support and lack of family support”.Subthemes of“lack of social support”were“inadequate leave,long distance from workplace,and insufficient wages”.Subthemes of“lack of family support”were“lack of spouse support,lack of spouse's family support,and lack of their family support”.Conclusions:Different socioeconomic factors influence childbearing tendency in working women.Social and family supports play an important role in this regard.It is important to take these factors into account at the time of policymaking in the field of midwifery.展开更多
Objective:To investigate the prevalence,mechanisms,and trends of knockdown resistance(kdr)in Anopheles(An.)culicifacies and its impact on the efficacy of organochlorine and other insecticides.Methods:A systematic revi...Objective:To investigate the prevalence,mechanisms,and trends of knockdown resistance(kdr)in Anopheles(An.)culicifacies and its impact on the efficacy of organochlorine and other insecticides.Methods:A systematic review was conducted based on PRISMA guidelines,extracting data from biooan.org,Embase,ProQuest,PubMed,Scopus,and Web of Science without a time limit until the end of 2022.Articles meeting the inclusion criteria were assessed using the STROBE checklist.Data on kdr mutations,insecticide resistance,and effectiveness were analyzed across eight selected studies from various regions.Results:The review revealed widespread kdr-mediated resistance in An.culicifacies,primarily against dichloro-diphenyl-trichloroethane(DDT),persisting even decades after discontinued use.Key kdr mutations,including L1014F and L1014S,were identified.Resistance to deltamethrin was less stable,with increased sensitivity observed after short-term discontinuation.The findings underscore the vector's sustained resistance to organochlorine insecticides and relative sensitivity to pyrethroids.Conclusions:Stable kdr resistance in An.culicifacies to organochlorine insecticides highlights the need for periodic susceptibility assessments and strategic rotation or combination of insecticides to combat malaria effectively and prevent the development of resistance.展开更多
Objective:To determine the efficacy of tranexamic acid(TXA)in the management of acute upper gastrointestinal(GI)bleeding.Methods:A total of 70 patients with acute upper GI bleeding were included in this double-blinded...Objective:To determine the efficacy of tranexamic acid(TXA)in the management of acute upper gastrointestinal(GI)bleeding.Methods:A total of 70 patients with acute upper GI bleeding were included in this double-blinded randomized controlled clinical trial from September 2018 to December 2018.Patients were divided into the control group(received fluid therapy and intravenous infusion of pantoprazole,35 cases)and the TXA group(received intravenous TXA besides the treatment of control group,35 cases).Rebleeding,admission duration,and need for blood transfusion were compared between the two groups.Results:Fifteen patients(42.9%)in the TXA group and 10 patients(28.6%)in the control group stayed in hospital for more than 3 days during their admission(P=0.21).Rebleeding occurred in 8 patients(22.9%)and 5 patients(14.3%)of the TXA group and the control group,respectively(P=0.35).More patients in the TXA group(21 cases,60%)received blood transfusion than the control group(8 cases,22.9%)(P=0.02).Conclusions:TXA did not improve the outcome of patients with acute upper GI bleeding.展开更多
Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC)from other tumors,mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatment...Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC)from other tumors,mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments,in order to improve the success rate of experimental therapies.Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies.Recently,clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients.Due to their frail status and sometimes fast-progressing disease,the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly,preventing their enrollment in clinical trials.However,the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients,and solid networks between research centers and referring institutions.An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials.Ultimately,institution of multidisciplinary teams can optimize treatment choice,biopsy timing,and quick enrollment of patients in clinical trials,before their performance status deteriorates.展开更多
Introduction: Testicular torsion is a surgical emergency which requires early diagnosis and prompt surgical management to avoid testicular damage. The aim of this study is to survey the clinical findings and outcome o...Introduction: Testicular torsion is a surgical emergency which requires early diagnosis and prompt surgical management to avoid testicular damage. The aim of this study is to survey the clinical findings and outcome of the patients treated for testicular torsion in a university hospital in Babol, northern Iran. Methods: In this cross sectional study, a retrospective survey of all cases presenting with acute scrotum and primarily diagnosed as testicular torsion was conducted during 2001 and 2012 in Babol, northern Iran. All 103 cases were reviewed and several clinical data, including duration of symptoms and operative findings were collected. Findings: Of 103 patients who presented to the emergency department with acute scrotum, the median age of the cases was 16.0 years. Thirty four percent of the patients presented emergency unit less than 6 hours from symptom exposure. Pain (95.1%) was the major symptom in all patients. Surgery revealed that 72 (70.9%) cases were diagnosed firmly as testicular torsion that 23 patients underwent orchidectomy for a necrotic torsed testis. There were significant differences between orchiectomized versus non-orchiectomized torsion cases in affected side, symptom presentation to operation time. Conclusion: According to our results more than half of the cases presented more than in the golden time. Late presentation to hospital was the major cause of delay leading to orchidectomy in patients with testicular torsion. Greater effort in health education and direct or selfreferal to hospital may reduce this delay.展开更多
Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in Chi...Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.展开更多
Objectives:The present study was conducted to evaluate the clinical competence and its related demographic factors among critical care nurses in Kermanshah,Iran.Methods:In this cross-sectional study,155 Iranian nurses...Objectives:The present study was conducted to evaluate the clinical competence and its related demographic factors among critical care nurses in Kermanshah,Iran.Methods:In this cross-sectional study,155 Iranian nurses were selected by stratified random sampling.The data collection tools included a personal information form and the"Nurse Competence Scale".Data were analyzed using descriptive and analytical statistics.Results:The mean score of nurses'clinical competence was equal to 76.14±1.59 out of 100,which was at a"very good level".The mean score of using clinical competence in practice was equal to 70.38±15.25 out of 100,which was at a"good level".Among the subscales of clinical competence,the highest mean score was related to"managing situation".The mean score of"using clinical competence in practice"was related to the subscale of"therapeutic interventions".There was no statistically significant difference among the score of clinical competence of nurses varying with different gender,age,academic degree,and work experience.Conclusions:The clinical competence of critical care nurses in Kermanshah was at a"very good"level,and the use of clinical competence in practice was at a"good level."Given the importance of clinical competencies in practice,nurses'clinical competence should be evaluated objectively and positive measures should be taken to promote the application of their clinical competence.展开更多
Cholangiocarcinoma(CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia with the highest incidence in northeastern Thailand. Chemotherapy of this type of cancer is limited due to the lack of effe...Cholangiocarcinoma(CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia with the highest incidence in northeastern Thailand. Chemotherapy of this type of cancer is limited due to the lack of effective chemotherapeutic drugs. A series of previous studies support further research and development of Atractylodes lancea(Thunb) DC.(AL) as a potential candidate for the treatment of CCA as a crude ethanolic extract. In the present study, we aimed to develop an oral pharmaceutical formulation(capsule) of the standardized AL crude ethanolic extract for further clinical development in patients with CCA. Major steps included macroscopic and microscopic authentication of the AL rhizomes, preparation of standardized AL extract, preparation of oral pharmaceutical formulation(capsule) of the standardized AL extract, quantitative and qualitative analysis of the marker compound(atractylodin) in the formulated AL extract, evaluation of contaminations of heavy metals, pesticides residues, and microorganisms in the ground AL rhizomes and the formulated(capsule) powder of AL, physicochemical and pharmaceutical properties of the formulated AL extract/capsule, and cytotoxicity evaluation of the formulated AL extract. Results of all evaluations confirmed satisfactory pharmaceutical properties of oral(capsule) formulation of the standardized AL extract.展开更多
The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shor...The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.展开更多
E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that was expected to be an antidiabetic agent. Its safety, tolerabil...E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that was expected to be an antidiabetic agent. Its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) were investigated in a randomized, double-blind, placebo-controlled, ascending single-dose study in 48 healthy Japanese male subjects. Fasted subjects were orally administered E3024 (5, 10, 20, 40, or 80 mg) or placebo. E3024 was rapidly absorbed, with tmax values ranging between 0.33 and 3 h after dosing. The mean t1/2 ranged from 5.34 to 11.68 h. AUC0-inf and Cmax increased dose-proportionately. PK-PD relationship of E3024 was evaluated by using an Imax model, indicating that plasma E3024 concentrations and inhibitory effects of plasma DPP-IV activity were well correlated. The IC50 value was calculated as 33.7 ng/mL, which was consistent with in vitro data. Thus, E3024 showed a good PK profile and inhibited DPP-IV dose-dependently. Of 30 subjects administered E3024, 12 (40%) experienced adverse events (AEs). Dose escalation to 160 mg was abandoned owing to undesired subjective/objective findings in 4 of 6 subjects receiving 40 mg and 5 of 6 subjects receiving 80 mg. The most prominent AE was rash, but there were no serious AEs or deaths. The maximum tolerated dose was considered to be 20 mg. We hypothesized that histamine was a cause of the rash induction, and examined blood histamine levels of normal Fischer rats treated with E3024. Blood histamine levels were increased significantly by E3024 at 500 mg/kg (p < 0.001), but not by vildagliptin or valine-pyrrolidide (DPP-IV inhibitors) at the same dose. No blood histamine increases were observed in genetically mast cell-deficient Ws/Ws rats treated with E3024 at 500 mg/kg. In in vitro assays, E3024 induced histamine release from normal rat peritoneal mast cells in a concentration-dependent manner, but not from basophils. The structure-activity relationship study suggested that a piperazine group N-linked to the 2-position of the 5,6-membered fused heterocyclic rings was a key structural element for triggering histamine release.展开更多
Objective:To determine patterns of antimicrobial resistance,analyze the prevalence of oxacillinase and molecular typing of strains of Acinetobacter baumannii(A.baumannii).Methods:A total of 121 strains of A.baumannii ...Objective:To determine patterns of antimicrobial resistance,analyze the prevalence of oxacillinase and molecular typing of strains of Acinetobacter baumannii(A.baumannii).Methods:A total of 121 strains of A.baumannii were obtained from patients admitted to Imam Hossein and Imam Khomeini Hospitals,Tehran,Iran,from January 2016 to November 2018.Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute recommendations.The presence of oxacillinase genes was assessed by polymerase chain reaction(PCR).To determine clonal relatedness,all isolates were subjected to repetitive sequence-based PCR(REP-PCR).Results:The isolates were obtained from 56(46.3%)males and 65(53.7%)females with the mean age of 39.5 years.Colistin with 100.0%sensitivity rate had the highest effect,while ceftriaxone with 16.5%sensitivity rate had the least effect on A.baumannii isolates.In addition,96(79.3%)and 99(81.8%)isolates were resistant to imipenem and meropenem,respectively.A total of 109 isolates(90.0%)exhibited multiple drug resistance with 10 different resistotypes.In total,75(75.7%)of carbapenem resistant isolates were positive for blaOXA-23-like,and 14(14.1%)for blaOXA-24-like gene.The five main clones A,B,C,D,and E were detected in 25(25.2%),36(36.4%),10(10.1%),8(8.0%),and 6(6.1%)of isolates,respectively.Conclusions:Carbapenem-resistant A.baumannii strains are high in the current study.To control the spread of carbapenem-resistant A.baumannii strains,regular monitoring programs are needed.展开更多
Drug abuse by pregnant women is one of the significant problems for mothers and their neonates.This study aimed to investigate the effects of maternal substance use disorder during pregnancy on neonatal developmental ...Drug abuse by pregnant women is one of the significant problems for mothers and their neonates.This study aimed to investigate the effects of maternal substance use disorder during pregnancy on neonatal developmental criteria.In a case-control study,clinical records of 90 neonates diagnosed with neonatal abstinence syndrome who were admitted to NICU in one of four hospitals affiliated with Shahid-Beheshti University of Medical Sciences in Tehran,Iran between 2017 and 2020 were compared to 90 neonates without neonatal abstinence syndrome(control group).Demographic information and data for neonatal developmental characteristics and complications were extracted from the clinical records of this convenience sample.Data for the type and method of maternal substance use during pregnancy were collected through a telephone call with mothers.Our data showed that the prevalence of drug addiction was 1.8%among pregnant women,and the most common drugs used by mothers were opium(n=45%,50%),amphetamine(n=30%,33%),and methadone(n=14%,16%).Neonates with abstinence syndrome had a higher prevalence of transient tachypnea of the newborn(TTN)(P=0.004),and a prevalence of being admitted to NICU(P=0.05)and for a longer duration(P<0.001).Their mothers had a higher prevalence of having pre-eclampsia(P=0.010).Using morphine vs.amphetamine showed no difference based on their effects on mothers and neonates.Substance use during pregnancy increased the prevalence of pregnancy complications(pre-eclampsia)and neonatal complications(TTN and prevalence and duration of hospitalization).Therefore,planning for the development of health policies to raise awareness among women and more broadly,all members of the community,is important to prevent the tendency to engage in this potentially high-risk behavior.展开更多
<strong>Background: </strong>Cardiac rehabilitation (CR) is a multifaceted treatment that can increase the survival and quality of life of cardiac patients by increasing their functional capacity (FC). In ...<strong>Background: </strong>Cardiac rehabilitation (CR) is a multifaceted treatment that can increase the survival and quality of life of cardiac patients by increasing their functional capacity (FC). In this study, we aimed to investigate the FC changes of cardiac patients after the CR program in different subgroups in terms of anthropometric, clinical, and psychological indices. <strong>Materials and Methods:</strong> This is a descriptive retrospective study that has been derived from the results of a Cohort study at the Rehabilitation Research Center of the Cardiovascular Research Institute of Isfahan (Iran), from 2006 to 2017. In this study, the dependent variable is functional capacity changes based on Mets obtained in exercise testing at the beginning and end of the CR program. Independent variables included age, sex, dyslipidemia, diabetes, smoking, and Body mass index, type of intervention, depression, and EF. <strong>Results:</strong> The sample size is 1250 cardiovascular patients, of which 917 (73.5%) are male and 331 (26.5%) are female. Functional capacity after the CR program significantly increased in all age, gender, body mass index, hypertension, hyperlipidemia, diabetes, smoking, depression, EF, and type of operation performed (angioplasty or open-heart surgery) subgroups, (p < 0.001). Using multiple linear regression analysis, a significant relationship was found between Mets changes and only the variables of gender, depression, and EF. <strong>Conclusion:</strong> The results of this study show the importance of rehabilitation programs in the secondary prevention of cardiovascular disease in different subgroups and factors such as gender, level of primary depression, and EF less than 35 are the most important factors affecting functional capacity increase after CR program in heart patients.展开更多
Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-co...Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.展开更多
Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
基金This study was financially supported by the Vice Chancellor for Research Affairs,Ilam University of Medical Sciences,Ilam,Iran(Project No.1326).
文摘Objective:To investigate the pattern of antibiotic resistance and biofilm production capabilities of clinical Acinetobacter baumannii(A.baumannii)isolates in this study.Methods:A.baumannii isolates were collected from Tehran Imam Khomeini Hospital in this cross-sectional study,and the minimum inhibitory concentrations for 16 antibiotics were determined using Vitek2®systems.All isolates were analyzed for biofilm production,then presence of biofilm-associated genes,and class Ⅰ and Ⅱ integron genes.Results:60 non-replicate A.baumannii isolates were included in this study.The resistance rates reached 100%for aztreonam,cefepime,ceftazidime,ciprofloxacin,piperacillin-tazobactam,piperacillin,ticarcillin,and trimethoprim-sulfamethoxazole.A.baumannii isolates were most sensitive to colistin and rifampicin being the most effective treatments.Multi-drug resistant and extensively drug-resistant isolates accounted for 83.3%and 16.7%,respectively.Of the isolates,91.6%formed biofilms,categorized as 10%strong,31.6%moderate,and 50%weak.No correlation was found between antibiotic resistance and biofilm formation.The genes csuE,abaI,and ompA were prevalent,but their distribution was similar across biofilm categories.A relationship between Int1 and biofilm production was noted.Conclusions:The high rates of antibiotic resistance and biofilm formation,alongside the presence of integrons including class Ⅰ and Ⅱ,underscore the necessity for ongoing monitoring of A.baumannii.Notably,classⅠintegron presence was significantly linked to biofilm formation.Further research is needed to explore the connection between antibiotic resistance and biofilm production in A.baumannii.
文摘Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.
文摘In 1993,the World Bank released a global report on the efficacy of health promotion,introducing the disability-adjusted life years(DALY)as a novel indicator.The DALY,a composite metric incorporating temporal and qualitative data,is grounded in preferences regarding disability status.This review delineates the algorithm used to calculate the value of the proposed DALY synthetic indicator and elucidates key methodological challenges associated with its application.In contrast to the quality-adjusted life years approach,derived from multi-attribute utility theory,the DALY stands as an independent synthetic indicator that adopts the assumptions of the Time Trade Off utility technique to define Disability Weights.Claiming to rely on no mathematical or economic theory,DALY users appear to have exempted themselves from verifying whether this indicator meets the classical properties required of all indicators,notably content validity,reliability,specificity,and sensitivity.The DALY concept emerged primarily to facilitate comparisons of the health impacts of various diseases globally within the framework of the Global Burden of Disease initiative,leading to numerous publications in international literature.Despite widespread adoption,the DALY synthetic indicator has prompted significant methodological concerns since its inception,manifesting in inconsistent and non-reproducible results.Given the substantial diffusion of the DALY indicator and its critical role in health impact assessments,a reassessment is warranted.This reconsideration is imperative for enhancing the robustness and reliability of public health decisionmaking processes.
文摘Introduction:The occurrence of congenital anomalies is one of the serious challenges in the world.Therefore,identifying related factors to reduce it is of particular importance.This study aimed to determine the incidence and factors related to congenital anomalies.Methods:An epidemiology study was conducted on 1567 infants and their parents in Kermanshah,Iran.The required information was extracted from the ffles of mothers in health centers.The data collection tool was a researcher-made checklist of 39 questions.The data was statistically analyzed with the STATA version 14 software.Result:The incidence of congenital anomalies was 2.9%(n=45).Brain anomalies(n=10)and pulmonary anomalies(n=8)were the most common congenital anomalies in newborns.The results showed that parents’age(p=0.001),place of residence(p=0.022),mother’s occupation(p=0.010),hemoglobin level(p=0.002),blood pressure disorders(p=0.001),bleeding during pregnancy(p=0.001),infection during pregnancy(p=0.001),multivitamins(p=0.002)and women’s previous birth records such as previous abnormal birth history(p=0.015),abortion history(p=0.001),stillbirth history(p=0.001),birth history of infant less than 2500 g(p=0.001)was found to have a statistically signiffcant relationship with congenital anomalies.Conclusion:The incidence of congenital anomalies was high in Kermanshah city.Considering the identiffcation of risk factors and preventive factors related to congenital anomalies,it is suggested that interventions be carried out in health centers to increase awareness among pregnant women to reduce the incidence of anomalies.
基金This study was supported by Kerman University of medical sciences,with grant number:95000387.
文摘Objective:To explain barriers to childbearing among working women from the perspective of working women and midwives.Methods:In this study,a qualitative study of content analysis method was employed.The study was conducted from December 2021 to July 2022.The population consisted of working women and midwives.Data collection was conducted using semi-structured interviews and continued until data saturation was achieved.Through purposeful sampling,10 women and 11 midwives were selected as the sample.The data were analyzed by Graneheim and Lundman content analysis approach.For more rigorous,Nvivo 14 software was also used for data management,analysis,coding and organization of data.Results:This study included 21 women(10 women employees and 11 midwives)aged 25-43 years(for women employees)and 27-56 years(for midwives)with 1 to 34 years of job experience.In examination of participant’views about the barriers to childbearing,1124 codes were identified,of which we managed to extract six subthemes and two themes.Two themes emerged:“lack of social support and lack of family support”.Subthemes of“lack of social support”were“inadequate leave,long distance from workplace,and insufficient wages”.Subthemes of“lack of family support”were“lack of spouse support,lack of spouse's family support,and lack of their family support”.Conclusions:Different socioeconomic factors influence childbearing tendency in working women.Social and family supports play an important role in this regard.It is important to take these factors into account at the time of policymaking in the field of midwifery.
文摘Objective:To investigate the prevalence,mechanisms,and trends of knockdown resistance(kdr)in Anopheles(An.)culicifacies and its impact on the efficacy of organochlorine and other insecticides.Methods:A systematic review was conducted based on PRISMA guidelines,extracting data from biooan.org,Embase,ProQuest,PubMed,Scopus,and Web of Science without a time limit until the end of 2022.Articles meeting the inclusion criteria were assessed using the STROBE checklist.Data on kdr mutations,insecticide resistance,and effectiveness were analyzed across eight selected studies from various regions.Results:The review revealed widespread kdr-mediated resistance in An.culicifacies,primarily against dichloro-diphenyl-trichloroethane(DDT),persisting even decades after discontinued use.Key kdr mutations,including L1014F and L1014S,were identified.Resistance to deltamethrin was less stable,with increased sensitivity observed after short-term discontinuation.The findings underscore the vector's sustained resistance to organochlorine insecticides and relative sensitivity to pyrethroids.Conclusions:Stable kdr resistance in An.culicifacies to organochlorine insecticides highlights the need for periodic susceptibility assessments and strategic rotation or combination of insecticides to combat malaria effectively and prevent the development of resistance.
基金financial support from Kermanshah University of Medical Sciences,Iran(Grant Number.97101).
文摘Objective:To determine the efficacy of tranexamic acid(TXA)in the management of acute upper gastrointestinal(GI)bleeding.Methods:A total of 70 patients with acute upper GI bleeding were included in this double-blinded randomized controlled clinical trial from September 2018 to December 2018.Patients were divided into the control group(received fluid therapy and intravenous infusion of pantoprazole,35 cases)and the TXA group(received intravenous TXA besides the treatment of control group,35 cases).Rebleeding,admission duration,and need for blood transfusion were compared between the two groups.Results:Fifteen patients(42.9%)in the TXA group and 10 patients(28.6%)in the control group stayed in hospital for more than 3 days during their admission(P=0.21).Rebleeding occurred in 8 patients(22.9%)and 5 patients(14.3%)of the TXA group and the control group,respectively(P=0.35).More patients in the TXA group(21 cases,60%)received blood transfusion than the control group(8 cases,22.9%)(P=0.02).Conclusions:TXA did not improve the outcome of patients with acute upper GI bleeding.
文摘Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC)from other tumors,mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments,in order to improve the success rate of experimental therapies.Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies.Recently,clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients.Due to their frail status and sometimes fast-progressing disease,the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly,preventing their enrollment in clinical trials.However,the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients,and solid networks between research centers and referring institutions.An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials.Ultimately,institution of multidisciplinary teams can optimize treatment choice,biopsy timing,and quick enrollment of patients in clinical trials,before their performance status deteriorates.
文摘Introduction: Testicular torsion is a surgical emergency which requires early diagnosis and prompt surgical management to avoid testicular damage. The aim of this study is to survey the clinical findings and outcome of the patients treated for testicular torsion in a university hospital in Babol, northern Iran. Methods: In this cross sectional study, a retrospective survey of all cases presenting with acute scrotum and primarily diagnosed as testicular torsion was conducted during 2001 and 2012 in Babol, northern Iran. All 103 cases were reviewed and several clinical data, including duration of symptoms and operative findings were collected. Findings: Of 103 patients who presented to the emergency department with acute scrotum, the median age of the cases was 16.0 years. Thirty four percent of the patients presented emergency unit less than 6 hours from symptom exposure. Pain (95.1%) was the major symptom in all patients. Surgery revealed that 72 (70.9%) cases were diagnosed firmly as testicular torsion that 23 patients underwent orchidectomy for a necrotic torsed testis. There were significant differences between orchiectomized versus non-orchiectomized torsion cases in affected side, symptom presentation to operation time. Conclusion: According to our results more than half of the cases presented more than in the golden time. Late presentation to hospital was the major cause of delay leading to orchidectomy in patients with testicular torsion. Greater effort in health education and direct or selfreferal to hospital may reduce this delay.
文摘Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.
基金This work was supported by the Kermanshah University of Medical Sciencesgrant numbers 96566
文摘Objectives:The present study was conducted to evaluate the clinical competence and its related demographic factors among critical care nurses in Kermanshah,Iran.Methods:In this cross-sectional study,155 Iranian nurses were selected by stratified random sampling.The data collection tools included a personal information form and the"Nurse Competence Scale".Data were analyzed using descriptive and analytical statistics.Results:The mean score of nurses'clinical competence was equal to 76.14±1.59 out of 100,which was at a"very good level".The mean score of using clinical competence in practice was equal to 70.38±15.25 out of 100,which was at a"good level".Among the subscales of clinical competence,the highest mean score was related to"managing situation".The mean score of"using clinical competence in practice"was related to the subscale of"therapeutic interventions".There was no statistically significant difference among the score of clinical competence of nurses varying with different gender,age,academic degree,and work experience.Conclusions:The clinical competence of critical care nurses in Kermanshah was at a"very good"level,and the use of clinical competence in practice was at a"good level."Given the importance of clinical competencies in practice,nurses'clinical competence should be evaluated objectively and positive measures should be taken to promote the application of their clinical competence.
基金Financial support by National Research Council of Thailand(NRCT)Center of Excellence in Pharmacology and Molecular Biology of Malaria+1 种基金Cholangiocarcinoma and Chulabhorn International College of Medicine(CICM)Thammasat University,Thailand
文摘Cholangiocarcinoma(CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia with the highest incidence in northeastern Thailand. Chemotherapy of this type of cancer is limited due to the lack of effective chemotherapeutic drugs. A series of previous studies support further research and development of Atractylodes lancea(Thunb) DC.(AL) as a potential candidate for the treatment of CCA as a crude ethanolic extract. In the present study, we aimed to develop an oral pharmaceutical formulation(capsule) of the standardized AL crude ethanolic extract for further clinical development in patients with CCA. Major steps included macroscopic and microscopic authentication of the AL rhizomes, preparation of standardized AL extract, preparation of oral pharmaceutical formulation(capsule) of the standardized AL extract, quantitative and qualitative analysis of the marker compound(atractylodin) in the formulated AL extract, evaluation of contaminations of heavy metals, pesticides residues, and microorganisms in the ground AL rhizomes and the formulated(capsule) powder of AL, physicochemical and pharmaceutical properties of the formulated AL extract/capsule, and cytotoxicity evaluation of the formulated AL extract. Results of all evaluations confirmed satisfactory pharmaceutical properties of oral(capsule) formulation of the standardized AL extract.
文摘The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.
文摘E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that was expected to be an antidiabetic agent. Its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) were investigated in a randomized, double-blind, placebo-controlled, ascending single-dose study in 48 healthy Japanese male subjects. Fasted subjects were orally administered E3024 (5, 10, 20, 40, or 80 mg) or placebo. E3024 was rapidly absorbed, with tmax values ranging between 0.33 and 3 h after dosing. The mean t1/2 ranged from 5.34 to 11.68 h. AUC0-inf and Cmax increased dose-proportionately. PK-PD relationship of E3024 was evaluated by using an Imax model, indicating that plasma E3024 concentrations and inhibitory effects of plasma DPP-IV activity were well correlated. The IC50 value was calculated as 33.7 ng/mL, which was consistent with in vitro data. Thus, E3024 showed a good PK profile and inhibited DPP-IV dose-dependently. Of 30 subjects administered E3024, 12 (40%) experienced adverse events (AEs). Dose escalation to 160 mg was abandoned owing to undesired subjective/objective findings in 4 of 6 subjects receiving 40 mg and 5 of 6 subjects receiving 80 mg. The most prominent AE was rash, but there were no serious AEs or deaths. The maximum tolerated dose was considered to be 20 mg. We hypothesized that histamine was a cause of the rash induction, and examined blood histamine levels of normal Fischer rats treated with E3024. Blood histamine levels were increased significantly by E3024 at 500 mg/kg (p < 0.001), but not by vildagliptin or valine-pyrrolidide (DPP-IV inhibitors) at the same dose. No blood histamine increases were observed in genetically mast cell-deficient Ws/Ws rats treated with E3024 at 500 mg/kg. In in vitro assays, E3024 induced histamine release from normal rat peritoneal mast cells in a concentration-dependent manner, but not from basophils. The structure-activity relationship study suggested that a piperazine group N-linked to the 2-position of the 5,6-membered fused heterocyclic rings was a key structural element for triggering histamine release.
文摘Objective:To determine patterns of antimicrobial resistance,analyze the prevalence of oxacillinase and molecular typing of strains of Acinetobacter baumannii(A.baumannii).Methods:A total of 121 strains of A.baumannii were obtained from patients admitted to Imam Hossein and Imam Khomeini Hospitals,Tehran,Iran,from January 2016 to November 2018.Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute recommendations.The presence of oxacillinase genes was assessed by polymerase chain reaction(PCR).To determine clonal relatedness,all isolates were subjected to repetitive sequence-based PCR(REP-PCR).Results:The isolates were obtained from 56(46.3%)males and 65(53.7%)females with the mean age of 39.5 years.Colistin with 100.0%sensitivity rate had the highest effect,while ceftriaxone with 16.5%sensitivity rate had the least effect on A.baumannii isolates.In addition,96(79.3%)and 99(81.8%)isolates were resistant to imipenem and meropenem,respectively.A total of 109 isolates(90.0%)exhibited multiple drug resistance with 10 different resistotypes.In total,75(75.7%)of carbapenem resistant isolates were positive for blaOXA-23-like,and 14(14.1%)for blaOXA-24-like gene.The five main clones A,B,C,D,and E were detected in 25(25.2%),36(36.4%),10(10.1%),8(8.0%),and 6(6.1%)of isolates,respectively.Conclusions:Carbapenem-resistant A.baumannii strains are high in the current study.To control the spread of carbapenem-resistant A.baumannii strains,regular monitoring programs are needed.
文摘Drug abuse by pregnant women is one of the significant problems for mothers and their neonates.This study aimed to investigate the effects of maternal substance use disorder during pregnancy on neonatal developmental criteria.In a case-control study,clinical records of 90 neonates diagnosed with neonatal abstinence syndrome who were admitted to NICU in one of four hospitals affiliated with Shahid-Beheshti University of Medical Sciences in Tehran,Iran between 2017 and 2020 were compared to 90 neonates without neonatal abstinence syndrome(control group).Demographic information and data for neonatal developmental characteristics and complications were extracted from the clinical records of this convenience sample.Data for the type and method of maternal substance use during pregnancy were collected through a telephone call with mothers.Our data showed that the prevalence of drug addiction was 1.8%among pregnant women,and the most common drugs used by mothers were opium(n=45%,50%),amphetamine(n=30%,33%),and methadone(n=14%,16%).Neonates with abstinence syndrome had a higher prevalence of transient tachypnea of the newborn(TTN)(P=0.004),and a prevalence of being admitted to NICU(P=0.05)and for a longer duration(P<0.001).Their mothers had a higher prevalence of having pre-eclampsia(P=0.010).Using morphine vs.amphetamine showed no difference based on their effects on mothers and neonates.Substance use during pregnancy increased the prevalence of pregnancy complications(pre-eclampsia)and neonatal complications(TTN and prevalence and duration of hospitalization).Therefore,planning for the development of health policies to raise awareness among women and more broadly,all members of the community,is important to prevent the tendency to engage in this potentially high-risk behavior.
文摘<strong>Background: </strong>Cardiac rehabilitation (CR) is a multifaceted treatment that can increase the survival and quality of life of cardiac patients by increasing their functional capacity (FC). In this study, we aimed to investigate the FC changes of cardiac patients after the CR program in different subgroups in terms of anthropometric, clinical, and psychological indices. <strong>Materials and Methods:</strong> This is a descriptive retrospective study that has been derived from the results of a Cohort study at the Rehabilitation Research Center of the Cardiovascular Research Institute of Isfahan (Iran), from 2006 to 2017. In this study, the dependent variable is functional capacity changes based on Mets obtained in exercise testing at the beginning and end of the CR program. Independent variables included age, sex, dyslipidemia, diabetes, smoking, and Body mass index, type of intervention, depression, and EF. <strong>Results:</strong> The sample size is 1250 cardiovascular patients, of which 917 (73.5%) are male and 331 (26.5%) are female. Functional capacity after the CR program significantly increased in all age, gender, body mass index, hypertension, hyperlipidemia, diabetes, smoking, depression, EF, and type of operation performed (angioplasty or open-heart surgery) subgroups, (p < 0.001). Using multiple linear regression analysis, a significant relationship was found between Mets changes and only the variables of gender, depression, and EF. <strong>Conclusion:</strong> The results of this study show the importance of rehabilitation programs in the secondary prevention of cardiovascular disease in different subgroups and factors such as gender, level of primary depression, and EF less than 35 are the most important factors affecting functional capacity increase after CR program in heart patients.
文摘Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
