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Antimicrobial Agents and Chemotherapy Jul 2019Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by parasites. Previous studies speculated that...
Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. A better understanding of the immunomodulatory effects of miltefosine is central to providing a rationale regarding synergistic mechanisms of activity to combine miltefosine optimally with other conventional and future antileishmanials that are currently under development. Therefore, a systematic literature search was performed to evaluate to what extent and how miltefosine influences the host Th1 response. Miltefosine's effects observed in both a preclinical and a clinical context associated with immunomodulation in the treatment of leishmaniasis are evaluated in this review. A total of 27 studies were included in the analysis. Based on the current evidence, miltefosine is not only capable of inducing direct parasite killing but also of modulating the host immunity. Our findings suggest that miltefosine-induced activation of Th1 cytokines, particularly represented by increased gamma interferon (IFN-γ) and interleukin 12 (IL-12), is essential to prevail over the -driven Th2 response. Differences in miltefosine-induced host-mediated effects between , animal model, and human studies are further discussed. All things considered, an effective treatment with miltefosine is acquired by enhanced functional Th1 cytokine responses and may further be enhanced in combination with immunostimulatory agents.
Topics: Animals; Antiprotozoal Agents; Cytokines; Humans; Immunomodulation; Leishmania; Leishmaniasis; Phosphorylcholine
PubMed: 31036692
DOI: 10.1128/AAC.02507-18 -
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 -
PLoS Neglected Tropical Diseases Dec 2018Case management in children with cutaneous leishmaniasis (CL) is mainly based on studies performed in adults. We aimed to determine the efficacy and harms of...
BACKGROUND
Case management in children with cutaneous leishmaniasis (CL) is mainly based on studies performed in adults. We aimed to determine the efficacy and harms of interventions to treat CL in children.
METHODS
We conducted a systematic review of clinical trials and cohort studies, assessing treatments of CL in children (≤12 years old). We performed structured searches in PubMed, CENTRAL, LILACS, SciELO, Scopus, the International Clinical Trials Registry Platform (ICTRP), clinicaltrials.gov and Google Scholar. No restrictions regarding ethnicity, country, sex or year of publication were applied. Languages were limited to English, Spanish and Portuguese. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A qualitative summary of the included studies was performed.
RESULTS
We identified 1092 records, and included 8 manuscripts (6 Randomized Clinical Trials [RCT] and 2 non-randomized studies). Most of the articles excluded in full-text review did not report outcomes separately for children. In American CL (ACL), 5 studies evaluated miltefosine and/or meglumine antimoniate (MA). Their efficacy varied from 68-83% and 17-69%, respectively. In Old-World CL (OWCL), two studies evaluated systemic therapies: rifampicin and MA; and one study assessed efficacy of cryotherapy (42%, Per Protocol [PP]) vs intralesional MA (72%, PP). Few studies (4) provided information on adverse events (AEs) for children, and no serious AEs were reported in participants. Risk of bias was generally low to unclear in ACL studies, and unclear to high in OWCL studies.
CONCLUSION
Information on efficacy of treatment for CL in children is scarce. There is an unmet need to develop specific formulations, surveillance of AEs, and guidelines both for the management of CL and clinical trials involving the pediatric population.
REGISTRATION
The protocol of this review was registered in the PROSPERO International register of systematic reviews, number CRD42017062164.
Topics: Antiprotozoal Agents; Clinical Trials as Topic; Humans; Leishmania; Leishmaniasis, Cutaneous; Meglumine Antimoniate; Phosphorylcholine; Rifampin
PubMed: 30550538
DOI: 10.1371/journal.pntd.0006986 -
International Immunopharmacology Jan 2019Proteins from parasitic worms have been posed as novel therapies for rheumatoid arthritis (RA) and other auto-inflammatory diseases. However, with so many potential... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Proteins from parasitic worms have been posed as novel therapies for rheumatoid arthritis (RA) and other auto-inflammatory diseases. However, with so many potential therapeutics, it is important that drug discovery be based on the specific phyla or species which show the most promising effects. Therefore, the aim of this systematic review and meta-analysis was to evaluate the reported effects of helminthic secretory proteins and derivative therapy on RA in an animal model.
METHODS
Medline, Scopus and Web of Science were searched to identify studies evaluating helminthic therapy in the collagen-induced arthritis model of RA. A meta-analysis was undertaken to determine the overall effect of the proteins. Subgroup analyses were also undertaken to investigate individual treatments.
RESULTS
Seven articles were included in the analysis. Overall, helminthic therapy significantly reduced arthritis score (SMD -1.193, 95% CI -1.525, -0.860). Subgroup analyses found a significant reduction in arthritis score following treatment with helminth protein ES-62 (SMD -1.186, 95% CI -1.633, -0.738) and phosphorylcholine-based treatment (SMD -0.997, 95% CI -1.423, -0.571). Subgroup analyses found ES-62 treatment significantly decreased IFN-γ levels (SMD -1.611, 95% CI -2.734, -0.487) and significantly increased levels of IL-10 (SMD 0.946, 95% CI 0.127, 1.765).
CONCLUSIONS
Therapeutics from parasitic worms are a promising avenue for drug discovery, especially with all included studies reporting a significant improvement in arthritis score. Based on pooled data presented in this study, the nematode Acanthocheilonema viteae seems to be of particular interest for therapeutics.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Disease Models, Animal; Helminth Proteins; Helminths; Humans; Mice; Rats; Therapy with Helminths
PubMed: 30529501
DOI: 10.1016/j.intimp.2018.11.034 -
Journal of Orthodontics Jun 2018The purpose of this study was to evaluate the efficacy of orthodontic bonding systems containing different antimicrobial agents, as well as the influence of... (Meta-Analysis)
Meta-Analysis
AIMS
The purpose of this study was to evaluate the efficacy of orthodontic bonding systems containing different antimicrobial agents, as well as the influence of antimicrobial agent incorporation in the bonding properties of these materials.
METHODS
Eight databases were searched: PubMed (Medline), Web of Science, Scopus, Lilacs, Ibecs, BBO, Scielo and Google Scholar. Any study that evaluated antimicrobial activity in experimental or commercial orthodontic bonding systems was included.
DATA EXTRACTION
Data were tabulated independently and in duplicated by two authors on pre-designed data collection form.
DATA SYNTHESIS
The global analysis was carried out using a random-effects model, and pooled-effect estimates were obtained by comparing the standardised mean difference of each antimicrobial orthodontic adhesive with the respective control group. A p-value < .05 was considered as statistically significant.
RESULTS
Thirty-two studies were included in the qualitative analysis; of these, 22 studies were included in the meta-analysis. Antimicrobial agents such as silver nanoparticles, benzalkonium chloride, chlorhexidine, triclosan, cetylpyridinium chloride, Galla chinensis extract, acid ursolic, dimethylaminododecyl methacrylate, dimethylaminohexadecyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine, 1,3,5-triacryloylhexahydro-1,3,5-triazine, zinc oxide and titanium oxide have been incorporated into orthodontic bonding systems. The antimicrobial agent incorporation in orthodontic bonding systems showed higher antimicrobial activity than the control group in agar diffusion (overall standardised mean difference: 3.71; 95% CI 2.98 to 4.43) and optical density tests (0.41; 95% CI -0.05 to 0.86) (p < .05). However, for biofilm, the materials did not present antimicrobial activity (6.78; 95% CI 4.78 to 8.77). Regarding bond strength, the global analysis showed antimicrobial orthodontic bonding systems were statistically similar to the control.
CONCLUSIONS
Although there is evidence of antibacterial activity from in vitro studies, clinical and long-term studies are still necessary to confirm the effectiveness of antibacterial orthodontic bonding systems in preventing caries disease.
Topics: Anti-Infective Agents; Dental Bonding; Materials Testing; Metal Nanoparticles; Resin Cements; Silver
PubMed: 29504867
DOI: 10.1080/14653125.2018.1443872 -
Clinical Microbiology and Infection :... Jun 2018To evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis.
METHODS
This systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488.
RESULTS
Thirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96-1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6-97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95-1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02-1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure.
CONCLUSIONS
AmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.
Topics: Amphotericin B; Antiprotozoal Agents; Clinical Trials as Topic; Deoxycholic Acid; Drug Combinations; Drug Compounding; Evidence-Based Medicine; Female; Humans; Leishmaniasis, Visceral; Male; Paromomycin; Phosphorylcholine; Survival Analysis; Treatment Outcome
PubMed: 29138100
DOI: 10.1016/j.cmi.2017.11.008 -
Cardiovascular Research Aug 2017An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the... (Meta-Analysis)
Meta-Analysis Review
An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease. An electronic search of five databases to June 2016 was performed by two independent reviewers. Inclusion criteria were analytical studies of adults, with at least two studies per autoantibody. Quality analysis was carried out using the Newcastle-Ottawa scale and the Cochrane Risk of Bias Quality Assessment Tool where appropriate. Where possible, studies were pooled using random effects models. Raised levels of anti-cardiolipin (odds ratio [OR] = 1.30; 95% CI: 1.15-1.49) and anti-oxidized low-density lipoprotein Immunoglobulin (Ig) G (OR = 1.25; 95% CI: 1.11-1.41), unspecified anti-cyclic citrullinated protein (OR = 3.09; 95% CI: 1.49-6.41) and anti-human heat shock protein 60 IgA (OR = 1.57; 95% CI: 1.15-2.16) were observed to increase the risk of cardiovascular outcomes. Alternatively, Anti-phosphorylcholine IgM (OR = 1.31; 95% CI: 1.14-1.50) conferred protection against CVD. Our results support an important role for autoantibodies in mediating cardiovascular events, independent of therapeutic treatments. Future research may focus on the presence of autoantibodies as markers of immune dysregulation and CVD risk.
Topics: Atherosclerosis; Autoantibodies; Autoimmune Diseases; Autoimmunity; Biomarkers; Humans; Odds Ratio; Protective Factors; Risk Assessment; Risk Factors
PubMed: 28899001
DOI: 10.1093/cvr/cvx112 -
The Cochrane Database of Systematic... May 2014Fungating wounds arise from primary, secondary or recurrent malignant disease and are associated with advanced cancer. A small proportion of patients may achieve healing... (Review)
Review
BACKGROUND
Fungating wounds arise from primary, secondary or recurrent malignant disease and are associated with advanced cancer. A small proportion of patients may achieve healing following surgical excision, but treatment is usually palliative. Fungating wound management usually aims to slow disease progression and optimise quality of life by alleviating physical symptoms, such as copious exudate, malodour, pain and the risk of haemorrhage, through selection of appropriate dressings and topical agents.
OBJECTIVES
To review the evidence of the effects of dressings and topical agents on quality of life, and symptoms that impact on quality of life, in people with fungating malignant wounds.
SEARCH METHODS
For this third update we searched the Wounds Group Specialised Register in August 2013; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL.
SELECTION CRITERIA
Eligible studies comprised randomised controlled trials (RCTs) or, in their absence, controlled clinical trials (CCTs) with a concurrent control group.
DATA COLLECTION AND ANALYSIS
Data extraction and risk of bias assessment was undertaken by one review author and checked for accuracy by a second.
MAIN RESULTS
Four trials involving 164 people were included. One RCT in women with superficial breast lesions compared 6% miltefosine solution with placebo and found that miltefosine delayed tumour progression. The study reported that the time to treatment failure was significantly longer in the miltefosine group (median 56 days) than in the placebo group (median 21 days) (p value 0.007, log-rank test). A second trial compared topical metronidazole with placebo but the results up to the point of cross-over were not statistically significant. A third trial compared the effect of foam dressings containing silver to foam dressings without silver and found that more patients experienced decreased malodour in the foam with silver group than in the foam alone group (p value=0.049). The fourth trial compared the effect of manuka honey-coated dressings with nanocrystalline silver-coated dressings and found no statistically significant difference with regard to exudate, malodour and wound pain. All trials, however, had methodological limitations.
AUTHORS' CONCLUSIONS
There is weak evidence from one small trial that 6% miltefosine solution applied topically to people with superficial fungating breast lesions (smaller than 1cm) who have received either previous radiotherapy, surgery, hormonal therapy or chemotherapy for their breast cancer, may slow disease progression. There is also weak evidence to suggest that foam dressings containing silver may be effective in reducing malodour. There is insufficient evidence in this review to give a clear direction for practice with regard to improving quality of life or managing wound symptoms associated with fungating wounds. More research is needed.
Topics: Anti-Infective Agents, Local; Antineoplastic Agents; Biological Dressings; Disease Progression; Female; Humans; Male; Metronidazole; Odorants; Ointments; Phosphorylcholine; Randomized Controlled Trials as Topic; Silver Compounds; Skin Neoplasms; Skin Ulcer; Wounds and Injuries
PubMed: 24832784
DOI: 10.1002/14651858.CD003948.pub3 -
The Cochrane Database of Systematic... Nov 2012Clinical trials have confirmed that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical trials have confirmed that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature newborns. Trials have studied a wide variety of surfactant preparations used either to prevent (prophylactic or delivery room administration) or treat (selective or rescue administration) respiratory distress syndrome (RDS). Using either treatment strategy, significant reductions in the incidence of pneumothorax, as well as significant improvement in survival, have been noted. It is unclear whether there are any advantages to treating infants with respiratory insufficiency earlier in the course of RDS.
OBJECTIVES
To compare the effects of early versus delayed selective surfactant therapy for newborns intubated for respiratory distress within the first two hours of life. Planned subgroup analyses included separate comparisons for studies utilizing natural surfactant extract and synthetic surfactant.
SEARCH METHODS
We searched the Oxford Database of Perinatal Trials, MEDLINE (MeSH terms: pulmonary surfactant; text word: early; limits: age, newborn: publication type, clinical trial), PubMed, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. For the updated search in April 2012 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1) and PubMed (January 1997 to April 2012).
SELECTION CRITERIA
Randomized and quasi-randomized controlled clinical trials comparing early selective surfactant administration (surfactant administration via the endotracheal tube in infants intubated for respiratory distress, not specifically for surfactant dosage) within the first two hours of life versus delayed selective surfactant administration to infants with established RDS were considered for review.
DATA COLLECTION AND ANALYSIS
Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on type of surfactant preparation, gestational age, and exposure to prenatal steroids. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
Six randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and four utilized animal-derived surfactant preparations.The meta-analyses demonstrate significant reductions in the risk of neonatal mortality (typical risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74 to 0.95; typical risk difference (RD) -0.04; 95% CI -0.06 to -0.01; 6 studies; 3577 infants), chronic lung disease (typical RR 0.69; 95% CI 0.55 to 0.86; typical RD -0.04; 95% CI -0.06 to -0.01; 3 studies; 3041 infants), and chronic lung disease or death at 36 weeks (typical RR 0.83; 95% CI 0.75 to 0.91; typical RD -0.06; 95% CI -0.09 to -0.03; 3 studies; 3050 infants) associated with early treatment of intubated infants with RDS.Intubated infants randomized to early selective surfactant administration also demonstrated a decreased risk of acute lung injury including a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59 to 0.82; typical RD -0.05; 95% CI -0.08 to -0.03; 5 studies; 3545 infants), pulmonary interstitial emphysema (typical RR 0.60; 95% CI 0.41 to 0.89; typical RD -0.06; 95% CI -0.10 to -0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR 0.61; 95% CI 0.48 to 0.78; typical RD -0.18; 95% CI -0.26 to -0.09; 2 studies; 463 infants).A trend toward risk reduction for bronchopulmonary dysplasia (BPD) or death at 28 days was also evident (typical RR 0.94; 95% CI 0.88 to 1.00; typical RD -0.04; 95% CI -0.07 to -0.00; 3 studies; 3039 infants). No differences in other complications of RDS or prematurity were noted.Only two studies reported on infants under 30 weeks' gestation. Decreased risk of neonatal mortality and chronic lung disease or death at 36 weeks' postmenstrual age was noted.
AUTHORS' CONCLUSIONS
Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop worsening RDS.
Topics: Acute Disease; Acute Lung Injury; Chronic Disease; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Lung Diseases; Phosphorylcholine; Polyethylene Glycols; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Time Factors
PubMed: 23152207
DOI: 10.1002/14651858.CD001456.pub2 -
Anais Brasileiros de Dermatologia 2011The therapeutic arsenal against cutaneous leishmaniasis is very limited. Pentavalent antimonial compounds have been the drugs of choice for treatment of this disease for... (Review)
Review
INTRODUCTION
The therapeutic arsenal against cutaneous leishmaniasis is very limited. Pentavalent antimonial compounds have been the drugs of choice for treatment of this disease for over 50 years. Despite their effectiveness, these drugs require daily injections, have many side effects and present prolonged healing time.
OBJECTIVE
To carry out a systematic literature review on the advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years.
METHODS
We conducted an electronic search on the Pubmed and LILACS database as well as on the SciELO electronic library in June 2009. The search words in English were: "cutaneous", "leishmaniasis" and "treatment". We included only randomized, double-blind and placebo controlled trials. We used the Jadad scale to assess the quality of the selected studies.
RESULTS
According to the inclusion and exclusion criteria, only eight articles were selected. The drugs evaluated in the selected studies were glucantime®, miltefosine, immunotherapy, imiquimod, rhGM-CSF and pentoxifylline, and paromomycin.
CONCLUSION
Although cutaneous leishmaniasis is a major public health issue, the published data on the use of new drugs for the treatment of cutaneous leishmaniasis in Brazil are still quite limited.
Topics: Aminoquinolines; Antiprotozoal Agents; Brazil; Developing Countries; Humans; Imiquimod; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Paromomycin; Pentoxifylline; Phosphorylcholine
PubMed: 21738967
DOI: 10.1590/s0365-05962011000300012