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European Review For Medical and... May 2016The present study aimed to investigate the effectiveness of atosiban in treating women with threatened preterm labor who had become pregnant through assisted... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The present study aimed to investigate the effectiveness of atosiban in treating women with threatened preterm labor who had become pregnant through assisted reproductive technology (ART) and the corresponding pregnancy outcomes.
PATIENTS AND METHODS
Seventy pregnant women with threatened preterm labor after ART were randomly divided into two groups, with 35 cases in the atosiban group and 35 in the ritodrine group. The post-treatment effects and the corresponding pregnancy outcomes were observed.
RESULTS
The efficacy of extending gestational age by 48 hours was significantly higher in the atosiban group than in the ritodrine group (p<0.05), whereas the efficacy of extending gestational age by seven days was the same in the two groups (p>0.05). There was no significant difference between the atosiban and ritodrine groups in the average gestational age at birth (p<0.05). The occurrence of side effects in the pregnant women was higher in the ritodrine group than in the atosiban group (p<0.05), although the prevalence of abnormal fetal heart rate was not significantly different (p>0.05). Both the perinatal mortality rate and the prevalence of neonatal asphyxia were significantly lower in the atosiban group than in the ritodrine group (p<0.05). When the medication was applied at a gestational age of fewer than 28 weeks, the perinatal mortality rate and the prevalence of neonatal pneumonia were significantly lower in the atosiban group compared with the ritodrine group (p<0.05). When the first drug administration was at a gestational age of 28 weeks or later, the need for neonatal pediatric treatment was significantly reduced in the atosiban group relative to the ritodrine group. Independent of when the drug administration was initiated, there were no significant differences between the atosiban and ritodrine groups in the occurrences of neonatal asphyxia, acute respiratory distress syndrome (ARDS), neonatal brain injury, or neonatal sepsis (p>0.05).
CONCLUSIONS
Administration of atosiban has a comparatively better effect than that of ritodrine on pregnant women who underwent ART and is safe and effective at preventing immediate preterm birth. Atosiban is significantly better than ritodrine at reducing the rates of perinatal mortality and neonatal pneumonia, and the perinatal outcomes for those who began to use atosiban at a gestational age of fewer than 28 weeks were even better.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Obstetric Labor, Premature; Pneumonia; Pregnancy; Reproductive Techniques, Assisted; Tocolytic Agents; Vasotocin
PubMed: 27212183
DOI: No ID Found -
International Journal of Molecular... Feb 2022The organic cation transporter 1 (OCT1, ) transports a large number of structurally diverse endogenous and exogenous substrates. There are numerous known competitive and...
The organic cation transporter 1 (OCT1, ) transports a large number of structurally diverse endogenous and exogenous substrates. There are numerous known competitive and non-competitive inhibitors of OCT1, but there are no studies systematically analyzing the relationship between transport, stimulation, and inhibition. Here, we tested in vitro OCT1 inhibition by OCT1 substrates and transport of OCT1 inhibitors under uniform analytical conditions. Beyond inhibition testing with two model substrates, we tested nine additional OCT1 substrates for their mutual inhibition. Inhibition of ASP uptake by most OCT1 substrates was weak. The model substrate sumatriptan, with its moderately stronger inhibitability, was used to confirm this. Interestingly, OCT1 substrates exhibiting stronger OCT1 inhibition were mainly biaromatic β-agonistic drugs, such as dobutamine, fenoterol, ractopamine and ritodrine. Biaromatic organic cations were both, strong inhibitors and good substrates, but many OCT1 substrates showed little pairwise inhibition. Surprisingly, sumatriptan did significantly enhance dobutamine uptake. This effect was concentration dependent and additional experiments indicated that efflux inhibition may be one of the underlying mechanisms. Our data suggests, that OCT1 substrates are mainly weak OCT1 inhibitors and among those inhibiting well, noncompetitive inhibition could be responsible. Weak competitive inhibition confirms that OCT1 inhibition screenings poorly predict OCT1 substrates. Additionally, we showed that the OCT1 substrate sumatriptan can enhance uptake of some other OCT1 substrates. OCT1 transport stimulation was already observed earlier but is still poorly understood. Low OCT1 uptake inhibition and strong OCT1 efflux inhibition could be mechanisms exploitable for enhancing transport.
Topics: Biological Transport; Cell Line; HEK293 Cells; Humans; Octamer Transcription Factor-1
PubMed: 35216120
DOI: 10.3390/ijms23042007 -
Experimental and Therapeutic Medicine Feb 2020Efficacy of allylestrenol combined with ritodrine on threatened premature labor (TPTL) and its influence on inflammatory factors in peripheral blood were investigated. A...
Efficacy of allylestrenol combined with ritodrine on threatened premature labor (TPTL) and its influence on inflammatory factors in peripheral blood were investigated. A total of 206 cases of TPTL patients from 2014 to 2016 were collected in Zhongshan Hospital Affiliated to Fudan University, and 106 cases were treated with allylestrenol combined with ritodrine as a research group and 100 cases were treated with allylestrenol combined with magnesium sulfate as a control group. General information of patients was collected, and changes in the expression levels of IL-17, IL-10 and IL-6 were detected by enzyme-linked immunosorbent assay. Prolonged pregnancy time, success rate of fetal protection and average delivery time of patients were recorded. The adverse pregnancy conditions were compared, including the Apgar score of newborns, birth weight and adverse conditions, and postpartum hemorrhage volume and postpartum hospital stays in the two groups were recorded. Prolonged pregnancy time, success rate of fetal protection and average delivery time in the research group were significantly higher than those in the control group (P<0.05). After treatment, the levels of IL-17, IL-10 and IL-6 in serum of the two groups were significantly lower than those before treatment (P<0.05), and were significantly lower in the research group than in the control group (P<0.05). The average neonatal weight and Apgar score in the research group were significantly better than those in the control group (P<0.05). Postpartum hemorrhage, postpartum hospital stays and incidence rate of toxic side effects, neonatal death, malformation and asphyxia in the research group were significantly lower than those in the control group (P<0.05). Allylestrenol combined with ritodrine can significantly reduce the expression levels of IL-17, IL-10 and IL-6 in TPTL, reduce adverse pregnancy conditions, prolong gestational weeks, and has higher safety and better application value.
PubMed: 32010251
DOI: 10.3892/etm.2019.8273 -
International Journal of Environmental... Jul 2021Postpartum depression (PPD) is associated with negative physical and mental health outcomes for the mother and infant. Women often experience elevated symptoms of PPD,...
Postpartum depression (PPD) is associated with negative physical and mental health outcomes for the mother and infant. Women often experience elevated symptoms of PPD, and the incidence of PPD has increased in recent years. There were lack of studies to investigate the effects of medications during pregnancy. Herein, we focused on the most common obstetric medical therapies used in labor and determined whether the medical therapies cause mental stress in pregnant women. This 14-year retrospective population-based nationwide study was based on the National Health Insurance Research Database. Univariate and multivariate logistic regression analyses were used to evaluate unadjusted and adjusted odds ratios and 95% confidence intervals for each tocolytic and uterotonic treatments during pregnancy and common medical illnesses. In comparing the effects of tocolytic and uterotonic medications on maternal PPD, tocolysis with the injection form of ritodrine resulted in a significantly higher risk of PPD based on multivariate analysis. This study supports existing research demonstrating an association between tocolysis with ritodrine and PPD. Ritodrine treatment for preterm labor was a significant risk factor for PPD, especially the injection form. This information provides obstetricians and health policy providers to pay attention to maternal mental health outcomes among high-risk pregnant women.
Topics: Depression, Postpartum; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Retrospective Studies; Risk Factors; Taiwan; Tocolysis
PubMed: 34281148
DOI: 10.3390/ijerph18137211 -
BMJ Open Dec 2017Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have...
OBJECTIVE
Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records.
DESIGN
Retrospective cohort study.
SETTING
Yamanashi Prefectural Central Hospital, Japan.
PARTICIPANTS
Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016.
METHODS
The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis.
OUTCOME MEASURES
Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver-operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence.
RESULTS
Mean maternal age was 32 (range, 18-46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%).
CONCLUSION
Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.
Topics: Adolescent; Adult; Cesarean Section; Delivery, Obstetric; Female; Humans; Japan; Logistic Models; Middle Aged; Obstetric Labor, Premature; Pregnancy; Pregnancy, Twin; Pulmonary Edema; ROC Curve; Retrospective Studies; Ritodrine; Tocolysis; Tocolytic Agents; Young Adult
PubMed: 29289935
DOI: 10.1136/bmjopen-2017-018118 -
Value in Health : the Journal of the... 2008In countries with high income, tocolytic therapy with beta-mimetic agents is a cost-effective strategy compared to placebo. In our study, the cost-effectiveness of two...
OBJECTIVES
In countries with high income, tocolytic therapy with beta-mimetic agents is a cost-effective strategy compared to placebo. In our study, the cost-effectiveness of two beta-mimetic agents, ritodrine and fenoterol, used in the management of preterm labor was compared in the setting of a low-middle-income transitional country, Serbia & Montenegro.
METHODS
This case study was conducted at the Gynecology-Obstetrics Clinic, Clinical Center "Kragujevac," in Kragujevac, Serbia & Montenegro, between October 2004 and January 2006. In total, 235 pregnant patients with threatened preterm labor were enrolled, but 35 were lost to follow-up. Of the remaining 200 patients, 85 were given ritodrine, and 115 fenoterol. The perspective of Republic Institute for Health Insurance in Serbia was taken into account. Only direct costs were calculated; primary outcomes of the study were length of pregnancy (in weeks), time passed from the onset of uterine contractions to delivery (in weeks), and score on modified Flanagan's quality-of-life scale for chronic diseases, measured after discharge from hospital.
RESULTS
Prolongation of pregnancy was significantly longer in the fenoterol group (12.7 +/- 8.4 weeks) than in the ritodrine group (11.6 +/- 7.1 weeks). The mean duration of hospitalization was shorter in the fenoterol group (11.9 +/- 8.8 days) than in the ritodrine group (14.9 +/- 11.3 days). The treatment with fenoterol was less costly and more cost-effective than the treatment with ritodrine, but the difference in cost-effectiveness was not statistically significant. The cost of treatment per gained week of pregnancy prolongation was 3345.51 +/- 7668.04 CSD in the fenoterol group, and 4181.96 +/- 12,069.83 CSD in the ritodrine group.
CONCLUSIONS
The observed differences in treatment costs and duration of hospitalization per patient did not translate into significant differences in cost-effectiveness ratios, because of low costs of hospitalization and human labor in Serbian health system. Nevertheless, fenoterol treatment still has a tendency to be more cost-effective, and its lower acquisition cost is an advantage to this treatment option.
Topics: Adult; Cohort Studies; Cost-Benefit Analysis; Female; Fenoterol; Hospitals, University; Humans; Montenegro; National Health Programs; Obstetric Labor, Premature; Pregnancy; Ritodrine; Social Class; Tocolytic Agents; Treatment Outcome; Yugoslavia
PubMed: 18380627
DOI: 10.1111/j.1524-4733.2007.00222.x -
The Cochrane Database of Systematic... Jun 2014Preterm birth, defined as birth between 20 and 36 completed weeks, is a major contributor to perinatal morbidity and mortality globally. Oxytocin receptor antagonists... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth, defined as birth between 20 and 36 completed weeks, is a major contributor to perinatal morbidity and mortality globally. Oxytocin receptor antagonists (ORA), such as atosiban, have been specially developed for the treatment of preterm labour. ORA have been proposed as effective tocolytic agents for women in preterm labour to prolong pregnancy with fewer side effects than other tocolytic agents.
OBJECTIVES
To assess the effects on maternal, fetal and neonatal outcomes of tocolysis with ORA for women with preterm labour compared with placebo or any other tocolytic agent.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013).
SELECTION CRITERIA
We included all randomised controlled trials (published and unpublished) of ORA for tocolysis of labour between 20 and 36 completed weeks' gestation.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated methodological quality and extracted trial data. When required, we sought additional data from trial authors. Results are presented as risk ratio (RR) for categorical and mean difference (MD) for continuous data with the 95% confidence intervals (CI). Where appropriate, the number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated.
MAIN RESULTS
This review update includes eight additional studies (790 women), giving a total of 14 studies involving 2485 women.Four studies (854 women) compared ORA (three used atosiban and one barusiban) with placebo. Three studies were considered at low risk of bias in general (blinded allocation to treatment and intervention), the fourth study did not adequately blind the intervention. No difference was shown in birth less than 48 hours after trial entry (average RR 1.05, 95% CI 0.15 to 7.43; random-effects, (two studies, 152 women), perinatal mortality (RR 2.25, 95% CI 0.79 to 6.38; two studies, 729 infants), or major neonatal morbidity. ORA (atosiban) resulted in a small reduction in birthweight (MD -138.86 g, 95% CI -250.53 to -27.18; two studies with 676 infants). In one study, atosiban resulted in an increase in extremely preterm birth (before 28 weeks' gestation) (RR 3.11, 95% CI 1.02 to 9.51; NNTH 31, 95% CI 8 to 3188) and infant deaths (up to 12 months) (RR 6.13, 95% CI 1.38 to 27.13; NNTH 28, 95% CI 6 to 377). However, this finding may be confounded due to randomisation of more women with pregnancy less than 26 weeks' gestation to atosiban. ORA also resulted in an increase in maternal adverse drug reactions requiring cessation of treatment in comparison with placebo (RR 4.02, 95% CI 2.05 to 7.85; NNTH 12, 95% CI 5 to 33). No differences were shown in preterm birth less than 37 weeks' gestation or any other adverse neonatal outcomes. No differences were evident by type of ORA, although data were limited.Eight studies (1402 women) compared ORA (atosiban only) with betamimetics; four were considered of low risk of bias (blinded allocation to treatment and to intervention). No statistically significant difference was shown in birth less than 48 hours after trial entry (RR 0.89, 95% CI 0.66 to 1.22; eight studies with 1389 women), very preterm birth (RR 1.70, 95% CI 0.89 to 3.23; one study with 145 women), extremely preterm birth (RR 0.84, 95% CI 0.37 to 1.92; one study with 244 women) or perinatal mortality (RR 0.55, 95% CI 0.21 to 1.48; three studies with 816 infants). One study (80 women), of unclear methodological quality, showed an increase in the interval between trial entry and birth (MD 22.90 days, 95% CI 18.03 to 27.77). No difference was shown in any reported measures of major neonatal morbidity (although numbers were small). ORA (atosiban) resulted in less maternal adverse effects requiring cessation of treatment (RR 0.05, 95% CI 0.02 to 0.11; NNTB 6, 95% CI 6 to 6; five studies with 1161 women).Two studies including (225 women) compared ORA (atosiban) with calcium channel blockers (CCB) (nifedipine only). The studies were considered as having high risk of bias as neither study blinded the intervention and in one study it was not known if allocation was blinded. No difference was shown in birth less than 48 hours after trial entry (average RR 1.09, 95% CI 0.44 to 2.73, random-effects; two studies, 225 women) and extremely preterm birth (RR 2.14, 95% CI 0.20 to 23.11; one study, 145 women). No data were available for the outcome of perinatal mortality. One small trial (145 women), which did not employ blinding of the intervention, showed an increase in the number of preterm births (before 37 weeks' gestation) (RR 1.56, 95% CI 1.13 to 2.14; NNTH 5, 95% CI 3 to 19), a lower gestational age at birth (MD -1.20 weeks, 95% CI -2.15 to -0.25) and an increase in admission to neonatal intensive care unit (RR 1.70, 95% CI 1.17 to 2.47; NNTH 5, 95% CI 3 to 20). ORA (atosiban) resulted in less maternal adverse effects (RR 0.38, 95% CI 0.21 to 0.68; NNTB 6, 95% CI 5 to 12; two studies, 225 women) but not maternal adverse effects requiring cessation of treatment (RR 0.36, 95% CI 0.01 to 8.62; one study, 145 women). No longer-term outcome data were included.
AUTHORS' CONCLUSIONS
This review did not demonstrate superiority of ORA (largely atosiban) as a tocolytic agent compared with placebo, betamimetics or CCB (largely nifedipine) in terms of pregnancy prolongation or neonatal outcomes, although ORA was associated with less maternal adverse effects than treatment with the CCB or betamimetics. The finding of an increase in infant deaths and more births before completion of 28 weeks of gestation in one placebo-controlled study warrants caution. However, the number of women enrolled at very low gestations was small. Due to limitations of small numbers studied and methodological quality, further well-designed randomised controlled trials are needed. Further comparisons of ORA versus CCB (which has a better side-effect profile than betamimetics) are needed. Consideration of further placebo-controlled studies seems warranted. Future studies of tocolytic agents should measure all important short- and long-term outcomes for women and infants, and costs.
Topics: Albuterol; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Obstetric Labor, Premature; Oligopeptides; Pregnancy; Randomized Controlled Trials as Topic; Receptors, Oxytocin; Ritodrine; Terbutaline; Tocolytic Agents; Vasotocin
PubMed: 24903678
DOI: 10.1002/14651858.CD004452.pub3 -
The Cochrane Database of Systematic... 2000Betamimetic drugs may promote fetal growth by increasing the availability of nutrients and by decreasing vascular resistance. They may also induce adverse effects via... (Review)
Review
BACKGROUND
Betamimetic drugs may promote fetal growth by increasing the availability of nutrients and by decreasing vascular resistance. They may also induce adverse effects via their effects on carbohydrate metabolism.
OBJECTIVES
The objective of this review was to assess the effects of betamimetic therapy for suspected impaired fetal growth on fetal growth and perinatal outcome.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of the latest search: December 1999.
SELECTION CRITERIA
Randomised trials of betamimetic therapy compared with no betamimetic therapy or placebo in women with suspected impaired fetal growth.
DATA COLLECTION AND ANALYSIS
Eligibility and trial quality was assessed.
MAIN RESULTS
Two studies of 118 women were included. No differences were found between the betamimetic groups and the control groups for low birth weight (relative risk 1.17, 95% confidence interval 0.75 to 1.83), other anthropometric or neonatal morbidity and mortality measures.
REVIEWER'S CONCLUSIONS
There is not enough evidence to evaluate the use of betamimetics in promoting fetal growth. Larger studies are needed to investigate possible adverse effects of long-term betamimetic administration.
Topics: Adrenergic beta-Agonists; Female; Fetal Growth Retardation; Humans; Pregnancy; Ritodrine; Tocolytic Agents
PubMed: 10796095
DOI: 10.1002/14651858.CD000036 -
Acta Obstetricia Et Gynecologica... 2008Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found no difference in psychosocial and motor functioning. In a randomised, multicentre trial, we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long-term follow-up of the newborns after 2 years of age.
METHODS
Patients with imminent preterm labour were randomised and received either nifedipine or ritodrine. Side-effects, tocolytic effectiveness and neonatal outcome were studied. Development of the children was studied after the age of 2 years by a parental questionnaire.
RESULTS
Ninety-three patients were included. Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group (p=0.4). Patients who received ritodrine experienced significantly more side-effects compared to patients who received nifedipine (29 versus 4%, p<0.05). No significant differences were found in either group for average birth weight, Apgar scores after 1 min, neonatal intensive care unit (NICU) admission and neonatal complications. Parental questionnaires after 2 years had a response rate of 70%. Two-thirds of the children had developed normally in both groups. In both groups, only a few children were severely retarded (n=4). No significant differences in development were found between the 2 groups.
CONCLUSIONS
Both nifedipine and ritodrine proved effective tocolytic drugs, however ritodrine caused significantly more maternal side-effects. Neonatal outcome and long-term development after 2 years of age were not significantly different. We favour nifedipine over ritodrine as a tocolytic drug.
Topics: Adrenergic beta-Agonists; Adult; Birth Weight; Calcium Channel Blockers; Child, Preschool; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Nifedipine; Obstetric Labor, Premature; Pregnancy; Ritodrine; Surveys and Questionnaires; Tocolysis; Tocolytic Agents
PubMed: 18307075
DOI: 10.1080/00016340801913189 -
Pesticide Biochemistry and Physiology Mar 2022New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal...
New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal screens of chemical collections have played an important role in the search for new vector insecticides and the identification of active ingredients (AIs) that cause rapid mortality of mosquitoes. Advances in image-based screening offer an opportunity to identify chemistries that operate via novel biochemical modes and investigate the range of phenotypes exhibited by mosquitoes following exposure to lethal and sub-lethal chemical dose. An automated, high throughput phenotypic screen (HTS) employing high-content imaging of first instar (L1) Aedes aegypti larvae was developed to identify chemistries associated with mortality and atypical morphological phenotypes. A pilot screen of the Library of Pharmacologically Active Compounds (LOPAC) identified 92 chemistries that disrupted larval activity and development, including conventional insecticides and chemistries known to modulate G protein-coupled receptors (GPCRs) and other molecular targets in mammalian systems. Secondary assay series were used to evaluate a selection of chemistries for impacts on mosquito activity, survival and development. Ritodrine hydrochloride reduced mobility of larvae but had no observable effect on survival and development of mosquitoes. High doses of metergoline suppressed larval activity and sub-lethal dose resulted in pupal mortality. Assay data support the utility of phenotypic screening and diverse entomological end-points for discovery of novel insecticidal chemical scaffolds. The insecticide discovery process must consider how multi-modal efficacy spectra contribute to vector and VBD control.
Topics: Aedes; Animals; Insecticides; Larva; Mosquito Control; Mosquito Vectors; Phenotype
PubMed: 35249647
DOI: 10.1016/j.pestbp.2022.105037