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Pharmacological Research Jan 2021Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness,...
Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness, elephantiasis and scabies. Satoshi ōmura and William C. Campbell won the 2015 Nobel Prize in Physiology or Medicine for the discovery of the excellent efficacy of ivermectin against parasitic diseases. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. This suggests that ivermectin may be an anticancer drug with great potential. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy.
Topics: Animals; Antineoplastic Agents; Antiparasitic Agents; Cell Death; Humans; Ivermectin; Molecular Targeted Therapy; Neoplasms; Signal Transduction
PubMed: 32971268
DOI: 10.1016/j.phrs.2020.105207 -
American Journal of Therapeutics Jun 2021Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials.
AREAS OF UNCERTAINTY
We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection.
DATA SOURCES
We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion.
THERAPEUTIC ADVANCES
Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19-0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian-Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff-Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%-91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for "need for mechanical ventilation," whereas effect estimates for "improvement" and "deterioration" clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.
CONCLUSIONS
Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.
Topics: Antiviral Agents; COVID-19; Humans; Ivermectin; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34145166
DOI: 10.1097/MJT.0000000000001402 -
Environment International Aug 2023Maternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive.
OBJECTIVES
To conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth.
DATA SOURCE
Five English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
To be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth.
STUDY APPRAISAL, SYNTHESIS METHODS AND CONFIDENCE ASSESSMENT
Quality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT.
RESULTS
A total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = -0.10; 95%CI: -0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P < 0.05). For studies that collected samples at any time during pregnancy, pesticide exposure was found to be associated with shortened length of gestational age (β = -0.43; 95%CI: -0.81, -0.06). The confidence rating in the body of evidence was "moderate" and "very low" for preterm birth and gestational age at birth, respectively.
CONCLUSION
Our result suggested moderate evidence of an association between pesticide exposure and higher risk of preterm birth. Yet more studies are still needed with larger sample size and careful considerations of confounders and accuracy of outcome measurements. Attention is also required on other pesticide compounds in addition to organochlorine and organophosphorus pesticides, and on windows of susceptibility.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Pesticides; Organophosphorus Compounds; Pregnancy Outcome; Gestational Age
PubMed: 37364307
DOI: 10.1016/j.envint.2023.108043 -
Toxics Apr 2022Rheumatoid arthritis (RA) is a disease that affects people all over the world and can be caused by a variety of factors. Exposure to pesticides is one of the risk... (Review)
Review
Rheumatoid arthritis (RA) is a disease that affects people all over the world and can be caused by a variety of factors. Exposure to pesticides is one of the risk factors for the development of RA. However, the evidence of exposure to pesticides linked with the development of RA is still controversial. This study aimed to investigate the association between exposure to pesticides and RA by a systematic review of relevant literature and a meta-analysis. Full-text articles published in PubMed, Web of Science, Scopus, and Google Scholar between 1956 and 2021 were reviewed and evaluated. A total of eight studies were eligible for inclusion (two cohort studies, four case-control studies, and two cross-sectional studies). The adjusted odds ratio for pesticide exposure on RA was 1.20 for insecticides (95% CI = 1.12-1.28), 0.98 for herbicides (95% CI = 0.89-1.08), 1.04 for fungicides (95% CI = 0.86-1.27), and 1.15 in for non-specific pesticides (95% CI = 1.09-1.21). There is some evidence to suggest that exposure to insecticides (especially fonofos, carbaryl, and guanidines) contributes to an increased risk of RA. However, the evidence is limited because of a small number of studies. Therefore, further epidemiological studies are needed to substantiate this conclusion.
PubMed: 35622621
DOI: 10.3390/toxics10050207 -
Environmental Research Dec 2022In low- and middle-income countries (LMICs), pesticides are widely used in agricultural and residential settings. Little is known about how pesticides affect child... (Review)
Review
BACKGROUND
In low- and middle-income countries (LMICs), pesticides are widely used in agricultural and residential settings. Little is known about how pesticides affect child growth.
OBJECTIVES
To systematically review and synthesise the evidence on the associations between pesticide exposure and adverse birth outcomes and/or impaired postnatal growth in children up to 5 years of age in LMICs.
METHODS
We searched 10 databases from inception through November 2021. We included cohort and cross-sectional studies investigating associations between self-reported or measured prenatal or postnatal pesticide exposure and child growth (postnatal child linear/ponderal growth, and/or birth outcomes). Two researchers screened studies, extracted data, and assessed certainty using GRADE. The protocol was preregistered with PROSPERO (CRD42021292919).
RESULTS
Of 939 records retrieved, 31 studies met inclusion criteria (11 cohort, 20 cross-sectional). All studies assessed prenatal exposure. Twenty-four studies reported on birth weight. Four found positive associations with organochlorines (0.01-0.25 standardised mean difference (SMD)) and two found negative associations (-0.009 SMD to -55 g). Negative associations with organophosphates (-170 g, n = 1) and pyrethroids (-97 to -233 g, n = 2) were also documented. Two (out of 15) studies reporting on birth length found positive associations with organochlorines (0.21-0.25 SMD) and one found negative associations (-0.25 to -0.32 SMD). Organophosphate exposure was negatively associated with birth length (-0.37 cm, n = 1). Organophosphate exposure was also associated with higher risk/prevalence of low birth weight (2 out of nine studies) and preterm birth (2 out of six studies). Certainty of the evidence was "very low" for all outcomes.
CONCLUSION
The limited literature from LMICs shows inconclusive associations between prenatal pesticide exposure, child growth, and birth outcomes. Studies with accurate quantitative data on exposure to commonly used pesticides in LMICs using consistent methodologies in comparable populations are needed to better understand how pesticides influence child growth.
Topics: Child; Cross-Sectional Studies; Developing Countries; Female; Humans; Infant, Newborn; Organophosphates; Pesticides; Pregnancy; Premature Birth; Pyrethrins
PubMed: 36087771
DOI: 10.1016/j.envres.2022.114230 -
Current Nutrition Reports Dec 2022This review aimed to investigate the association of sustainable diets in relation to cancer risk, cancer recurrence, and cancer-specific mortality in adults. (Review)
Review
PURPOSE OF REVIEW
This review aimed to investigate the association of sustainable diets in relation to cancer risk, cancer recurrence, and cancer-specific mortality in adults.
RECENT FINDINGS
More than 500 articles were initially identified. Nine articles were eligible for inclusion, presenting data from 8 prospective cohort studies, conducted in Europe and the USA. The sustainability indicators investigated were greenhouse gas emissions, food biodiversity, land use, exposure to pesticides or organic food consumption, and the EAT-Lancet diet. One study reported a sustainability index that combined multiple sustainability indicators. A modest inverse association between higher adherence to sustainable diets and cancer incidence or cancer mortality was observed in most studies. While sustainable diets may decrease cancer risk or mortality, the reviewed studies were heterogeneous regarding sustainability indicators and cancer outcomes. A common definition of dietary sustainability would facilitate better generalization of future research findings. Also, studies among non-western populations are needed.
Topics: Adult; Humans; Prospective Studies; Diet; Food Supply; Food; Neoplasms
PubMed: 36409441
DOI: 10.1007/s13668-022-00442-z -
British Journal of Clinical Pharmacology Apr 2021Numerous algorithms have been developed to guide warfarin dosing and improve clinical outcomes. We reviewed the algorithms available for various populations and the... (Review)
Review
AIMS
Numerous algorithms have been developed to guide warfarin dosing and improve clinical outcomes. We reviewed the algorithms available for various populations and the covariates, performances and risk of bias of these algorithms.
METHODS
We systematically searched MEDLINE up to 20 May 2020 and selected studies describing the development, external validation or clinical utility of a multivariable warfarin dosing algorithm. Two investigators conducted data extraction and quality assessment.
RESULTS
Of 10 035 screened records, 266 articles were included in the review, describing the development of 433 dosing algorithms, 481 external validations and 52 clinical utility assessments. Most developed algorithms were for dose initiation (86%), developed by multiple linear regression (65%) and mostly applicable to Asians (49%) or Whites (43%). The most common demographic/clinical/environmental covariates were age (included in 401 algorithms), concomitant medications (270 algorithms) and weight (229 algorithms) while CYP2C9 (329 algorithms), VKORC1 (319 algorithms) and CYP4F2 (92 algorithms) variants were the most common genetic covariates. Only 26% and 7% algorithms were externally validated and evaluated for clinical utility, respectively, with <2% of algorithm developments and external validations being rated as having a low risk of bias.
CONCLUSION
Most warfarin dosing algorithms have been developed in Asians and Whites and may not be applicable to under-served populations. Few algorithms have been externally validated, assessed for clinical utility, and/or have a low risk of bias which makes them unreliable for clinical use. Algorithm development and assessment should follow current methodological recommendations to improve reliability and applicability, and under-represented populations should be prioritized.
Topics: Algorithms; Anticoagulants; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Genotype; Humans; Pharmacogenetics; Reproducibility of Results; Vitamin K Epoxide Reductases; Warfarin
PubMed: 33080066
DOI: 10.1111/bcp.14608 -
Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
PloS One 2023Despite considerable evidence on a negative association between pregnancy pesticide exposure and child development in high-income countries, evidence from low- and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite considerable evidence on a negative association between pregnancy pesticide exposure and child development in high-income countries, evidence from low- and middle-income countries (LMICs) is limited. Therefore, we assessed associations between pregnancy pesticide exposure and child development in rural Bangladesh and summarised existing literature in a systematic review and meta-analysis.
METHODS
We used data from 284 mother-child pairs participating in a birth cohort established in 2008. Eight urinary pesticide biomarkers were quantified in early pregnancy (mean gestational age 11.6±2.9 weeks) as an index of pesticide exposure. The Bayley Scales of Infant and Toddler Development, Third Edition were administered at 20-40 months of age. Associations between creatinine-adjusted urinary pesticide biomarker concentrations and child development scores were estimated using multivariable generalised linear models. We searched ten databases up to November 2021 to identify prospective studies on pregnancy pesticide exposure and child development conducted in LMICs. We used a random-effects model to pool similar studies, including our original analysis. The systematic review was pre-registered with PROSPERO: CRD42021292919.
RESULTS
In the Bangladesh cohort, pregnancy 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY) concentrations were inversely associated with motor development (-0.66 points [95% CI -1.23, -0.09]). Pregnancy 3,5,6-trichloro-2-pyridinol (TCPY) concentrations were inversely associated with cognitive development, but the association was small: -0.02 points (-0.04, 0.01). We observed no associations between 4-nitrophenol and 3-phenoxybenzoic acid (3-PBA) concentrations and child development. The systematic review included 13 studies from four LMICs. After pooling our results with one other study, we found consistent evidence that pregnancy 3-PBA concentrations were not associated with cognitive, language, or motor development.
CONCLUSION
Evidence suggests that pregnancy exposure to some organophosphate pesticides is negatively associated with child development. Interventions to reduce in-utero pesticide exposure in LMICs may help protect child development.
Topics: Pregnancy; Infant; Female; Humans; Pesticides; Developing Countries; Child Development; Birth Cohort; Prospective Studies; Bangladesh
PubMed: 37294794
DOI: 10.1371/journal.pone.0287089 -
The Cochrane Database of Systematic... Oct 2022Malaria remains an important public health problem. Research in 1900 suggested house modifications may reduce malaria transmission. A previous version of this review... (Review)
Review
BACKGROUND
Malaria remains an important public health problem. Research in 1900 suggested house modifications may reduce malaria transmission. A previous version of this review concluded that house screening may be effective in reducing malaria. This update includes data from five new studies.
OBJECTIVES
To assess the effects of house modifications that aim to reduce exposure to mosquitoes on malaria disease and transmission.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS) up to 25 May 2022. We also searched the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry to identify ongoing trials up to 25 May 2022.
SELECTION CRITERIA
Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We sought studies investigating primary construction and house modifications to existing homes reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We extracted any entomological outcomes that were also reported in these studies.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
One RCT and six cRCTs met our inclusion criteria, with an additional six ongoing RCTs. We did not identify any eligible non-randomized studies. All included trials were conducted in sub-Saharan Africa since 2009; two randomized by household and four at the block or village level. All trials assessed screening of windows, doors, eaves, ceilings, or any combination of these; this was either alone, or in combination with roof modification or eave tube installation (an insecticidal "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In one trial, the screening material was treated with 2% permethrin insecticide. In five trials, the researchers implemented the interventions. A community-based approach was adopted in the other trial. Overall, the implementation of house modifications probably reduced malaria parasite prevalence (RR 0.68, 95% CI 0.57 to 0.82; 5 trials, 5183 participants; moderate-certainty evidence), although an inconsistent effect was observed in a subpopulation of children in one study. House modifications reduced moderate to severe anaemia prevalence (RR 0.70, 95% CI 0.55 to 0.89; 3 trials, 3643 participants; high-certainty evidence). There was no consistent effect on clinical malaria incidence, with rate ratios ranging from 0.38 to 1.62 (3 trials, 3365 participants, 4126.6 person-years). House modifications may reduce indoor mosquito density (rate ratio 0.63, 95% CI 0.30 to 1.30; 4 trials, 9894 household-nights; low-certainty evidence), although two studies showed little effect on this parameter.
AUTHORS' CONCLUSIONS
House modifications - largely screening, sometimes combined with insecticide and lure and kill devices - were associated with a reduction in malaria parasite prevalence and a reduction in people with anaemia. Findings on malaria incidence were mixed. Modifications were also associated with lower indoor adult mosquito density, but this effect was not present in some studies.
Topics: Adult; Anemia; Animals; Child; Culicidae; Humans; Insecticides; Malaria; Permethrin
PubMed: 36200610
DOI: 10.1002/14651858.CD013398.pub4