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PloS One 2021Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can...
Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators-if any-included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.
Topics: Allylamine; Animals; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Prognosis
PubMed: 33826660
DOI: 10.1371/journal.pone.0249628 -
PLoS Neglected Tropical Diseases Mar 2021Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs).
METHODS
For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression.
RESULTS
We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041-0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001-2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368-1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021-0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244-1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020-0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections.
CONCLUSION
Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.
Topics: Amphotericin B; Antimony; Antiprotozoal Agents; Deoxycholic Acid; Drug Combinations; Humans; Leishmaniasis, Visceral; Phosphorylcholine
PubMed: 33780461
DOI: 10.1371/journal.pntd.0009302 -
Acta Parasitologica Sep 2021In recent years, antimonial agents and other synthetic antileishmanial drugs, such as amphotericin B, paromomycin, and many other drugs, have restrictions in use due to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, antimonial agents and other synthetic antileishmanial drugs, such as amphotericin B, paromomycin, and many other drugs, have restrictions in use due to the toxicity risk, high cost, and emerging resistance to these drugs. The present study aimed to review the antileishmanial effects of curcumin, its derivatives, and other relevant pharmaceutical formulations on leishmaniasis.
METHODS
The present study was carried out according to the 06-preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. Some English-language databases including PubMed, Google Scholar, Web of Science, EBSCO, Science Direct, and Scopus were searched for publications worldwide related to antileishmanial effects of curcumin, its derivatives, and other relevant pharmaceutical formulations, without date limitation, to identify all the published articles (in vitro, in vivo, and clinical studies). Keywords included "curcumin", "Curcuma longa", "antileishmanial", "Leishmania", "leishmaniasis", "cutaneous leishmaniasis", "visceral leishmaniasis", "in vitro", and "in vivo".
RESULTS
Out of 5492 papers, 29 papers including 20 in vitro (69.0%), 1 in vivo (3.4%), and 8 in vitro/in vivo (27.6%) studies conducted up to 2020, met the inclusion criteria for discussion in this systematic review. The most common species of the Leishmania parasite used in these studies were L. donovani (n = 13, 44.8%), L. major (n = 10, 34.5%), and L. amazonensis (n = 6, 20.7%), respectively. The most used derivatives in these studies were curcumin (n = 15, 33.3%) and curcuminoids (n = 5, 16.7%), respectively.
CONCLUSION
In the present review, according to the studies in the literature, various forms of drugs based on curcumin and their derivatives exhibited significant in vitro and in vivo antileishmanial activity against different Leishmania spp. The results revealed that curcumin and its derivatives could be considered as an alternative and complementary source of valuable antileishmanial components against leishmaniasis, which had no significant toxicity. However, further studies are required to elucidate this concluding remark, especially in clinical settings.
Topics: Antiprotozoal Agents; Curcumin; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral
PubMed: 33770343
DOI: 10.1007/s11686-021-00351-1 -
International Journal of Molecular... Dec 2020The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum... (Meta-Analysis)
Meta-Analysis
The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.
Topics: Biomarkers; Case-Control Studies; Female; Humans; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Schizophrenia; Schizophrenic Psychology; Trace Elements
PubMed: 33334078
DOI: 10.3390/ijms21249566 -
Clinical Toxicology (Philadelphia, Pa.) Jul 2021On 5 May 2021 we celebrate the bicentenary of Napoleon's death. Despite autopsy findings of a "gastric cancer" and, more importantly, gastric perforated ulcer...
INTRODUCTION
On 5 May 2021 we celebrate the bicentenary of Napoleon's death. Despite autopsy findings of a "gastric cancer" and, more importantly, gastric perforated ulcer complicated with bleeding, the questions about the illness that tormented Napoleon at St. Helena and whether the death was a consequence of a poisoning, maintain an unbroken fascination. PubMed/MEDLINE lists hundreds of articles. We also consulted Index-Cat library for articles dating back to the eighteenth century. The present paper presents for the first time a systematic review on this topic.
METHODS
The authors divided the selected articles according to the methodology of the papers: (a) illness and autopsy evidence revised by current pathological knowledge; (b) toxicological tests on Napoleon's hair performed by modern analytical techniques.
RESULTS
None of the articles denied the toxicological evidence from Napoleon's hair, although analytical papers did not offer homogeneous results due to several biases. Few of them refuted the hypothesis of death due to primary toxic substances. Most considered gastric bleeding is the primary cause of Napoleon's death due to solely or nearly completely gastric cancer or to medications containing antimony, mercury, or arsenic.
CONCLUSIONS
Upon review of the contemporary and modern evidence, we classify Napoleon's 1821 death as "unnatural" with massive gastric bleeding due to primary involvement of toxic substances that may have precipitated or exacerbated an underlying "natural" pathological condition or a disease as likely could be a stomach carcinoma; it does not imply criminal intent.
Topics: Arsenic Poisoning; Cause of Death; Famous Persons; Gastrointestinal Hemorrhage; Hair; Humans; Stomach Neoplasms
PubMed: 33267676
DOI: 10.1080/15563650.2020.1843658 -
The Cochrane Database of Systematic... Aug 2020On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.
OBJECTIVES
To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).
SEARCH METHODS
We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic
PubMed: 32853410
DOI: 10.1002/14651858.CD004834.pub3 -
Environmental Health Perspectives Mar 2020Electronic cigarettes (e-cigarettes) have become popular, in part because they are perceived as a safer alternative to tobacco cigarettes. An increasing number of...
BACKGROUND
Electronic cigarettes (e-cigarettes) have become popular, in part because they are perceived as a safer alternative to tobacco cigarettes. An increasing number of studies, however, have found toxic metals/metalloids in e-cigarette emissions.
OBJECTIVE
We summarized the evidence on metal/metalloid levels in e-cigarette liquid (e-liquid), aerosols, and biosamples of e-cigarette users across e-cigarette device systems to evaluate metal/metalloid exposure levels for e-cigarette users and the potential implications on health outcomes.
METHODS
We searched PubMed/TOXLINE, Embase®, and Web of Science for studies on metals/metalloids in e-liquid, e-cigarette aerosols, and biosamples of e-cigarette users. For metal/metalloid levels in e-liquid and aerosol samples, we collected the mean and standard deviation (SD) if these values were reported, derived mean and SD by using automated software to infer them if data were reported in a figure, or calculated the overall mean (mean ± SD) if data were reported only for separate groups. Metal/metalloid levels in e-liquids and aerosols were converted and reported in micrograms per kilogram and nanograms per puff, respectively, for easy comparison.
RESULTS
We identified 24 studies on metals/metalloids in e-liquid, e-cigarette aerosols, and human biosamples of e-cigarette users. Metal/metalloid levels, including aluminum, antimony, arsenic, cadmium, cobalt, chromium, copper, iron, lead, manganese, nickel, selenium, tin, and zinc, were present in e-cigarette samples in the studies reviewed. Twelve studies reported metal/metalloid levels in e-liquids (bottles, cartridges, open wick, and tank), 12 studies reported metal/metalloid levels in e-cigarette aerosols (from cig-a-like and tank devices), and 4 studies reported metal/metalloid levels in human biosamples (urine, saliva, serum, and blood) of e-cigarette users. Metal/metalloid levels showed substantial heterogeneity depending on sample type, source of e-liquid, and device type. Metal/metalloid levels in e-liquid from cartridges or tank/open wicks were higher than those from bottles, possibly due to coil contact. Most metal/metalloid levels found in biosamples of e-cigarette users were similar or higher than levels found in biosamples of conventional cigarette users, and even higher than those found in biosamples of cigar users.
CONCLUSION
E-cigarettes are a potential source of exposure to metals/metalloids. Differences in collection methods and puffing regimes likely contribute to the variability in metal/metalloid levels across studies, making comparison across studies difficult. Standardized protocols for the quantification of metal/metalloid levels from e-cigarette samples are needed. https://doi.org/10.1289/EHP5686.
Topics: Aerosols; Electronic Nicotine Delivery Systems; Humans; Metalloids; Metals; Saliva
PubMed: 32186411
DOI: 10.1289/EHP5686 -
Journal of the European Academy of... Oct 2020Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the... (Meta-Analysis)
Meta-Analysis Review
Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first-line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side-effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two-arm or three-arm design in which one of the arms consisted in a combination of a drug/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re-epithelization and/or negative direct smear. Our literature search identified 554 references. Thirty-one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11-1.35, I = 64%). In association with PA, the comparator-specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25-1.81, I = 57%) and allopurinol (RR: 1.70 95% CI: 1.37-2.12, I = 28%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88-1.32, I = 40%) and pentoxifylline (RR: 1.14 95% CI: 0.94-1.40, I = 41%) revealed a non-significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99-1.73, I = 84%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre-existing drugs/interventions with PA. According to our results, the combination of allopurinol-PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod-PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy-PA-TCA or allopurinol-PA-cryotherapy or allopurinol-PA-TCA can represent promising treatments yet to be confirmed in future trials.
Topics: Combined Modality Therapy; Cryotherapy; Humans; Imiquimod; Leishmaniasis, Cutaneous; Photochemotherapy
PubMed: 32118322
DOI: 10.1111/jdv.16333 -
International Journal of Environmental... Nov 2019Antimony (Sb) trioxide and antimony trisulfide are "2B: Possibly carcinogenic to humans" and "3: Unclassifiable" according to the International Agency for Research on...
BACKGROUND
Antimony (Sb) trioxide and antimony trisulfide are "2B: Possibly carcinogenic to humans" and "3: Unclassifiable" according to the International Agency for Research on Cancer (IARC). The U.S. National Toxicology Program (NTP) concluded that antimony trioxide "is reasonably anticipated to be a human carcinogen based on studies in rats and mice". We investigated the cancer hazard of antimony compounds for workers, a population with high exposure to antimony substances.
METHODS
Using the "Guidelines for performing systematic reviews in the development of toxicity factors" (Texas Commission on Environmental Quality (TCEQ) 2017) as a guidance, we established a human and an animal toxicology data stream in Medline and ToxLine. Data from this review were applied in a human health risk assessment.
RESULTS
A final pool of 10 occupational and 13 animal toxicology articles resulted after application of TCEQ guidelines.
CONCLUSIONS
Antimony carcinogenicity evidence involving workers is inadequate, based on confounding, small sample sizes, incomparability across studies, and inadequate reference populations. An increased lung cancer risk cannot be excluded. Evidence for lung neoplasms caused by antimony trioxide inhalation in experimental animals is sufficient. Overall, carcinogenicity in workers is probable (International Agency for Research on Cancer (IARC) 2A). It remains unclear from what occupational exposure duration and dose this effect arises and whether exposure threshold values should be reconsidered.
Topics: Animals; Antimony; Carcinogens; Humans; Mice; Models, Animal; Neoplasms; Occupational Exposure; Rats; Risk Assessment; Texas
PubMed: 31739404
DOI: 10.3390/ijerph16224474 -
Epidemiology and Health 2019Cutaneous leishmaniasis (CL) is most common form of leishmaniasis and is characterized by ulcerative skin lesions. The objective of this study was to conduct a... (Meta-Analysis)
Meta-Analysis
Cutaneous leishmaniasis (CL) is most common form of leishmaniasis and is characterized by ulcerative skin lesions. The objective of this study was to conduct a systematic review and meta-analysis of clinical trials that compared the efficacy of miltefosine and glucantime for the treatment of CL. We searched the following databases: Cochrane, PubMed, Embase, Scopus, Web of Science, ProQuest, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform search portal of World Health Organization, Sid, Irandoc, Magiran, and clinicaltrials.gov. We used keywords including "miltefosine," "glucantime," and "Leishmania." The quality of studies was assessed using the Cochrane risk of bias tool. A random-effects model was employed for the analysis. We assessed heterogeneity by the chi-square test and the I2 index statistic. When heterogeneity was present, meta-regression analyses were performed. The Egger method was used to assess publication bias; when it was significant, the trim-and-fill method was used to test and adjust for publication bias. A total of 1,570 reports were identified, of which 10 studies were included in the meta-analysis. In the meta-analysis, there was no significant difference between the efficacy of miltefosine and glucantime; however, subgroup analysis showed that, regarding parasite species other than Leishmania braziliensis, miltefosine was significantly superior to glucantime (intention to treat; relative risk, 1.15; 95% confidence interval, 1.01 to 1.32). In the meta-regression, only the glucantime injection type was significant at the p=0.1 level. The Egger test found statistically significant publication bias; however, including the 3 missing studies in the trim-and-fill analysis did not change the results. This meta-analysis found that miltefosine seems to be more effective than glucantime, at least in species other than L. braziliensis, for treating CL.
Topics: Humans; Leishmaniasis, Cutaneous; Meglumine Antimoniate; Non-Randomized Controlled Trials as Topic; Phosphorylcholine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30999735
DOI: 10.4178/epih.e2019011