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Clinical Epigenetics 2015Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective... (Review)
Review
Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.
PubMed: 25984247
DOI: 10.1186/s13148-015-0055-7 -
Current Environmental Health Reports Dec 2016Published systematic reviews concluded that there is moderate to strong evidence to infer a potential role of lead and cadmium, widespread environmental metals, as... (Review)
Review
Published systematic reviews concluded that there is moderate to strong evidence to infer a potential role of lead and cadmium, widespread environmental metals, as cardiovascular risk factors. For other non-essential metals, the evidence has not been appraised systematically. Our objective was to systematically review epidemiologic studies on the association between cardiovascular disease in adults and the environmental metals antimony, barium, chromium, nickel, tungsten, uranium, and vanadium. We identified a total of 4 articles on antimony, 1 on barium, 5 on chromium, 1 on nickel, 4 on tungsten, 1 on uranium, and 0 on vanadium. We concluded that the current evidence is not sufficient to inform on the cardiovascular role of these metals because of the small number of studies. Few experimental studies have also evaluated the role of these metals in cardiovascular outcomes. Additional epidemiologic and experimental studies, including prospective cohort studies, are needed to understand the role of metals, including exposure to metal mixtures, in cardiovascular disease development.
Topics: Cadmium; Cardiovascular Diseases; Environmental Exposure; Environmental Pollutants; Humans; Lead; Metals; Risk Factors
PubMed: 27783356
DOI: 10.1007/s40572-016-0117-9 -
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 -
World Journal of Surgical Oncology May 2017Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical... (Meta-Analysis)
Meta-Analysis Review
Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of diagnostic studies.
BACKGROUND
Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical operation and assure the oncologic safety of the function or stomach preserving surgery. The diagnostic performance of this technology in recent studies varied. Thus, we conducted this meta-analysis.
METHODS
This systematic review and meta-analysis was registered at the PROSPERO. Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and Cochrane Library databases. A random-effect model was used to pool the data. Summary receiver operator characteristic curves, analysis for publication bias, meta-regression, and subgroup analysis were also performed.
RESULTS
The pooled SLN identification rate and sensitivity were 0.97 and 0.89. Tc-human serum albumin with indocyanine green (ICG), Tc-antimony sulfur colloid with ICG, performing SLN biopsy ≥15 min after dye injection, an SLN ≥5, the basin dissection, laparoscopic surgery, in studies conducted in Japan and studies published after 2012, were associated with higher sensitivity. CT1 stage, performing SLN biopsy ≥15 min after dye injection, in studies conducted in Japan and studies published after 2012, were related with a higher identification rate.
CONCLUSIONS
Dual tracer is promising in SLN biopsy in gastric cancer, and the clinical application of SLN biopsy should be limited to the patients of cT1N0M0 gastric cancer. The combination of Tc-human serum albumin and ICG as well as the combination of Tc-antimony sulfur colloid and ICG may be the optimal tracer combination. However, it seems not justified to put this technique into routine clinical application recently. Some factors that might enhance diagnostic value are identified.
Topics: Feasibility Studies; Humans; Neoplasm Staging; Prognosis; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Stomach Neoplasms
PubMed: 28511723
DOI: 10.1186/s12957-017-1159-7 -
The Cochrane Database of Systematic... Nov 2017Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008.
OBJECTIVES
To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis.
SEARCH METHODS
We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE.
SELECTION CRITERIA
Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search.
MAIN RESULTS
We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons.
AUTHORS' CONCLUSIONS
There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.
Topics: Animals; Anti-Infective Agents; Antiprotozoal Agents; Complementary Therapies; Cryotherapy; Hot Temperature; Humans; Itraconazole; Laser Therapy; Leishmania major; Leishmania tropica; Leishmaniasis, Cutaneous; Paromomycin; Photochemotherapy; Randomized Controlled Trials as Topic
PubMed: 29149474
DOI: 10.1002/14651858.CD005067.pub4 -
The Cochrane Database of Systematic... Dec 2017Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008.
OBJECTIVES
To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis.
SEARCH METHODS
We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE.
SELECTION CRITERIA
Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search.
MAIN RESULTS
We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons.
AUTHORS' CONCLUSIONS
There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.
Topics: Adult; Animals; Anti-Infective Agents; Antiprotozoal Agents; Complementary Therapies; Cryotherapy; Asia, Eastern; Female; Hot Temperature; Humans; Itraconazole; Laser Therapy; Leishmania major; Leishmania tropica; Leishmaniasis, Cutaneous; Male; Middle Aged; Middle East; Ointment Bases; Paromomycin; Photochemotherapy; Randomized Controlled Trials as Topic
PubMed: 29192424
DOI: 10.1002/14651858.CD005067.pub5 -
BMC Medicine May 2009Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.
METHODS
All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.
RESULTS
We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.
CONCLUSION
Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.
Topics: Blood Chemical Analysis; Humans; Plasma; Renal Dialysis; Serum; Trace Elements
PubMed: 19454005
DOI: 10.1186/1741-7015-7-25 -
Acta Tropica May 2011Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and... (Review)
Review
Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and pentamidine. Although these drugs have been used for decades, there are no systematic reviews about their safety. The objective of this review was to identify and classify the main adverse effects associated with these drugs and to estimate the frequency of these effects, whenever possible. Intervention studies, case series and case reports containing information regarding clinical, laboratory or electrocardiographic adverse effects of drugs used for the treatment of cutaneous leishmaniasis were systematically retrieved from 10 databases searched between August 13, 2008 and March 31, 2009. The 65 studies included in this review had treated a total of 4359 patients from 12 countries infected with eight different Leishmania species. Despite the small number of drugs used in these studies, a wide variability in the therapeutic regimens was observed. As a consequence, the adverse effects of pentavalent antimonials and pentamidine needed to be classified jointly according to system, irrespective of formulation, daily dose, duration of treatment, and route of administration. The frequencies of adverse effects were calculated based on the data of 32 articles involving 1866 patients. The most frequently reported clinical adverse effects of pentavalent antimonials and pentamidine were musculoskeletal pain, gastrointestinal disturbances, and mild to moderate headache. Electrocardiographic QTc interval prolongation and a mild to moderate increase in liver and pancreatic enzymes were additional adverse effects of pentavalent antimonials. Patients treated with liposomal amphotericin B had mild dyspnea and erythema. The adverse effects associated with miltefosine were vomiting, nausea, kinetosis, headache, diarrhea, and a mild to moderate increase in aminotransferases and creatinine. Although closer surveillance is needed for the treatment of cutaneous leishmaniasis, antileishmanial drugs are basically safe and severe side effects requiring the discontinuation of treatment are relatively uncommon.
Topics: Amphotericin B; Antimony; Antiprotozoal Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Leishmaniasis, Cutaneous; Pentamidine
PubMed: 21420925
DOI: 10.1016/j.actatropica.2011.02.007 -
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 -
PloS One 2017The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their... (Review)
Review
BACKGROUND
The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment.
METHODOLOGY
The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible.
RESULTS
Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6-96.1%) and 83,2% (95%CI 66-92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68-81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66-82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75-90%) versus 68% (95%CI 54-79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%), OR: 3.14 (95%CI 1.1-8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73%) versus 82% (95%CI 70-89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates.
CONCLUSIONS
Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.
Topics: Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Cryotherapy; Databases, Factual; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Treatment Outcome
PubMed: 28926630
DOI: 10.1371/journal.pone.0184777