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Acta Ophthalmologica May 2017Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal... (Meta-Analysis)
Meta-Analysis Review
Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Ultraviolet Rays
PubMed: 27678078
DOI: 10.1111/aos.13224 -
Photodiagnosis and Photodynamic Therapy Jun 2021SARS-CoV-2, which causes the coronavirus disease (COVID-19), presents high rates of morbidity and mortality around the world. The search to eliminate SARS-CoV-2 is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
SARS-CoV-2, which causes the coronavirus disease (COVID-19), presents high rates of morbidity and mortality around the world. The search to eliminate SARS-CoV-2 is ongoing and urgent. This systematic review seeks to assess whether photodynamic therapy (PDT) could be effective in SARS-CoV-2 inactivation.
METHODS
The focus question was: Can photodynamic therapy be used as potential guidance for dealing with SARS-CoV-2?". A literature search, according to PRISMA statements, was conducted in the electronic databases PubMed, EMBASE, SCOPUS, Web of Science, LILACS, and Google Scholar. Studies published from January 2004 to June 2020 were analyzed. In vitro and in vivo studies were included that evaluated the effect of PDT mediated by several photosensitizers on RNA and DNA enveloped and non-enveloped viruses.
RESULTS
From 27 selected manuscripts, 26 publications used in vitro studies, 24 were exclusively in vitro, and two had in vitro/in vivo parts. Only one analyzed publication was exclusively in vivo. Meta-analysis studies were unfeasible due to heterogeneity of the data. The risk of bias was analyzed in all studies.
CONCLUSION
The in vitro and in vivo studies selected in this systematic review indicated that PDT is capable of photoinactivating enveloped and non-enveloped DNA and RNA viruses, suggesting that PDT can potentially photoinactivate SARS-CoV-2.
Topics: Antiviral Agents; COVID-19; Humans; Photochemotherapy; Photosensitizing Agents; SARS-CoV-2
PubMed: 33601001
DOI: 10.1016/j.pdpdt.2021.102221 -
Clinical Oral Investigations Apr 2023Periodontal disease and diabetes have an extensively investigated bidirectional correlation. Non-surgical periodontal treatment (NSPT) was proven to contribute to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Periodontal disease and diabetes have an extensively investigated bidirectional correlation. Non-surgical periodontal treatment (NSPT) was proven to contribute to glycemic control. Moreover, it may benefit from the association of adjunctive therapies. The aim of the present systematic review is to assess the clinical efficacy of NSPT in association with laser (LT) or photodynamic therapy (PDT) in controlled or uncontrolled diabetic patients, and to grade the level of evidence.
MATERIALS AND METHODS
Randomized controlled clinical trials with at least 3-month follow-up were searched in MEDLINE via OVID, EMBASE, and Cochrane Central, screened for inclusion, and grouped based on the performed treatments, follow-up time, type of diabetes, and level of glycemic control.
RESULTS
Eleven RCTs with 504 total subjects were included. The adjunct of PDT showed a statistically significant 6-month difference in PD changes (with low certainty of evidence), but not in CAL changes, while a significant difference in 3-month PD and CAL changes was found with the adjunct of LT (low certainty of evidence). Patients treated with PDT registered a higher decrease in HbA1c levels at 3 months, but no significant difference was noted at 6 months; LT also led to better HbA1c changes at 3 months with a moderate certainty of evidence.
CONCLUSION
Despite the promising short-term HbA1c decrease, the results should be interpreted with caution due to the small effect sizes and the statistical heterogeneity, and further evidence from well-designed RCTs is needed to support the routine use of PDT or LT in adjunct to NSPT.
Topics: Humans; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Periodontitis; Periodontal Diseases; Photochemotherapy; Chronic Periodontitis; Dental Scaling
PubMed: 36849595
DOI: 10.1007/s00784-023-04873-y -
Photodiagnosis and Photodynamic Therapy Dec 2022Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an... (Review)
Review
BACKGROUND
Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an emerging antitumor strategy, photodynamic therapy (PDT) mediated by visible and near infrared light has attracted intensive attention given its target selectivity, remote controllability, minimal or non-invasive features. However, PDT also has obvious limitations. Specifically, due to the limited penetration of light, it is mainly used in the clinical treatment of superficial malignant tumours, such as musculoskeletal sarcomas and melanoma, but it has not been applied to the clinical treatment of deep malignant bone tumours except for a very small number of experiments on deep canine OS models.
MATERIALS AND METHODS
We searched for studies that focused on the effectiveness and safety of PDT for OS based on in vitro experiments and animal models in the last decade. A systematic search was conducted using electronic databases, including PubMed, ClinicalTrials.gov, and the Cochrane Library.
INCLUSION CRITERIA
(1) original research articles about PDT for OS; (2) articles in English; (3) in vitro or animal model research; and (4) detailed information, including cell name, fluence, irradiation wavelength, time of incubation with PS, duration between PS treatment and irradiation, and duration between irradiation and viability assays.
EXCLUSION CRITERIA
(1) study was a review/systemic review article, patent, letter, or conference abstract/paper; (2) articles were not published in English; (3) studies containing overlapping or insufficient data.
RESULTS
We identified 201 publications, and 44 articles met the inclusion criteria and were included in the synthesis. Unfortunately, there are no relevant clinical reports of the use of PDT in the treatment of human OS. In these studies, 8 studies only employed in vivo experiments to evaluate the efficiency of PDT in an OS animal model, 19 studies exclusively performed in vitro viability assays of cells treated with PDT under different conditions, and 17 studies included in vitro cell experiments and in vivo animal OS models to evaluate the effect of PDT on OS in vivo and in vitro. All studies have shown that PDT is cytotoxic to OS cells or can inhibit the growth of OS in heterologous or homologous animal OS models but exhibits minimal cytotoxicity at a certain range of dosages.
CONCLUSION
Based on this systematic review, PDT can eradicate OS cells in cell culture and there is some evidence for efficacy in animal models. However, the ability for PDT to control human OS is unclear, the animal and human reports do not show evidence of human OS control, they just do show feasibility. The major issues concerning the potential for treatment of osteosarcoma with PDT are that adequate light should be transmitted to tumor loci and if the disease is caught before metastasis and irradiation of tumor sites is feasible, curative potential is there. Otherwise, PDT may be mainly palliative. To determine whether PDT can safely and efficiently be used in the clinical treatment of OS, many preclinical orthotopic animal OS models and OS models of multiple systemic metastases must be performed and interstitial PDT or intraoperative PDT may be a good and potential candidate for human OS treatment. If these problems can be well solved, PDT may be a potentially effective strategy for the treatment of OS patients.
Topics: Humans; Animals; Dogs; Photochemotherapy; Photosensitizing Agents; Osteosarcoma; Bone Neoplasms; Models, Animal; Cell Line, Tumor
PubMed: 36031143
DOI: 10.1016/j.pdpdt.2022.103093 -
The Cochrane Database of Systematic... Jan 2013Neovascular age-related macular degeneration (AMD) is associated with rapid vision loss due to choroidal neovascularization (CNV), leakage, and scarring. Steroids have... (Review)
Review
BACKGROUND
Neovascular age-related macular degeneration (AMD) is associated with rapid vision loss due to choroidal neovascularization (CNV), leakage, and scarring. Steroids have gained attention in their role for the treatment of neovascular AMD for their antiangiogenic and anti-inflammatory properties.
OBJECTIVES
This review aims to examine effects of steroids with antiangiogenic properties in the treatment of neovascular AMD.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2012), EMBASE (January 1980 to November 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2012.
SELECTION CRITERIA
We included randomized controlled clinical trials of intra- and peri-ocular antiangiogenic steroids in people diagnosed with neovascular AMD.
DATA COLLECTION AND ANALYSIS
Two authors independently screened abstracts and full-text articles, assessed risk of bias in the included trials, and extracted data. We did not conduct a meta-analysis.
MAIN RESULTS
We included three trials after screening a total of 1503 abstracts and 21 full-text articles. The three trials included a total of 809 participants. One trial compared different doses of acetonide anecortave acetate with placebo, a second trial compared triamcinolone acetonide versus placebo, and the third trial compared anecortave acetate against photodynamic therapy (PDT). We did not conduct a meta-analysis owing to heterogeneity of interventions and comparisons. The risk ratio for loss of 3 or more lines of vision at 12 months follow-up was 0.8 (95% confidence interval (CI) 0.45 to 1.45) with 3 mg anecortave acetate, 0.45 (95% CI = 0.21 to 0.97) with 15 mg anecortave acetate, 0.91 (0.52 to 1.58) with 30 mg anecortave acetate, 0.97 (95% CI 0.74 to 1.26) with triamcinolone acetonide, all compared to placebo and 1.08 (95% CI 0.91 to 1.29) with anecortave acetate compared with PDT.
AUTHORS' CONCLUSIONS
Based on the included trials, we found no evidence that antiangiogenic steroids prevent visual loss in patients with neovascular AMD. With the emergence of anti-vascular endothelial growth factor modalities, based on evidence summarized in this review, it is unclear what role steroids have in treating patients with neovascular AMD.
Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Drug Implants; Humans; Macular Degeneration; Photochemotherapy; Pregnadienediols; Randomized Controlled Trials as Topic; Triamcinolone Acetonide
PubMed: 23440797
DOI: 10.1002/14651858.CD005022.pub3 -
Prostate International Sep 2019Photodynamic therapy (PDT) is an emerging focal treatment modality for prostate cancer. However, the efficacy, safety, and functional outcomes of PDT are not clear. We... (Review)
Review
PURPOSE
Photodynamic therapy (PDT) is an emerging focal treatment modality for prostate cancer. However, the efficacy, safety, and functional outcomes of PDT are not clear. We performed a meta-analysis of available single-arm studies and control trials which used PDT for prostate cancer.
MATERIALS AND METHODS
We searched Pubmed, Embase, Ovid and the Cochrane library (until March,2018) for studies about PDT in patients with prostate cancer. The negative biopsy rate after PDT, PSA decreasing rate, pooled rate of functional outcome (IPSS or IIEF-5), and adverse events were analyzed.
RESULTS
14 studies containing 654 patients were included. Nine of the 14 included studies had evaluated a negative biopsy rate after PDT. The pooled rate was 55.0% (95.0% CI: 0.44-0.66, I = 85.7%). Twelve of the 14 included studies which evaluated PSA decreasing rate with the pooled rate of 35.0% (95.0% CI: 0.24-0.47, I = 88.7%). Six of the included studies evaluated IPSS with decreasing rate of 29.1% (95.0 % CI: 2.7%-55.5%, I = 96.9%). Five of the included studies evaluated IIEF-5 with decreasing rate of 14.9% (95.0% CI: 6.8%-23.0%, I = 44.2%). The most common adverse events were haematuria (28.1%, 95.0% CI: 17.1%-39.2%, I = 79.8%), erectile dysfunction (23.1%, 95.0% CI: 9.7%-36.5%, I = 87.7%), and dysuria (18.6%, 95.0% CI: 12.1%-25.0 %, I = 53.4 %).
CONCLUSIONS
The meta-analysis results shows that PDT for patients with prostate cancer can be considered as effective based on single-arm clinical trials. Meanwhile, this study reveals that there are not only low levels of side effect rates but also insignificant effect on both urinary and erectile function. However, more high-quality RCTs are needed to evaluate the comparative efficacy, safety, and functional outcomes of PDT for patients with prostate cancer.
PubMed: 31485431
DOI: 10.1016/j.prnil.2018.12.002 -
BMC Oral Health Oct 2023To evaluate the clinical efficacy of photodynamic therapy (PDT) as an adjunct or alternative to traditional antifungal drugs in the treatment of oral candidiasis, and to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the clinical efficacy of photodynamic therapy (PDT) as an adjunct or alternative to traditional antifungal drugs in the treatment of oral candidiasis, and to provide evidence-based medical evidence for its use in the treatment of oral candidiasis.
METHODS
Computer combined with manual retrieval of China Academic Journals Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Science and Technology Journal Database (VIP), Wanfang Database, PubMed, Web of Science, Cochrane Library, Embase, Scopus retrieval for articles published before January 2023, basic information and required data were extracted according to the inclusion and exclusion criteria, and the Revman V5.4 software was used to conduct Meta-analysis of the included literature.
RESULTS
A total of 11 articles were included, 7 of which used nystatin as an antifungal drug, 2 of which were combined treatment of PDT and nystatin, 2 of the remaining 4 articles were treated with fluconazole, and 2 were treated with miconazole. Meta results showed that PDT was superior to nystatin in reducing the number of oral candida colonies in the palate of patients MD = -0.87, 95%CI = (-1.52,-0.23), P = 0.008, the difference was statistically significant, and the denture site MD = -1.03, 95%CI = (-2.21, -0.15), P = 0.09, the difference was not statistically significant; compared with the efficacy of fluconazole, RR = 1.01, 95%CI = (0.56,1.83), P = 0.96; compared with miconazole RR = 0.55, 95%CI = (0.38, 0.81), P = 0.002; PDT combined with nystatin RR = 1.27, 95%CI = (1.06, 1.52), P = 0.01; recurrence rate RR = 0.28, 95%CI = (0.09, 0.88), P = 0.03.
CONCLUSIONS
PDT was effective in the treatment of oral candidiasis; PDT was more effective than nystatin for the treatment of denture stomatitis in the palate, while there was no significant difference between the two for the denture site; The efficacy of PDT for oral candidiasis was similar to that of fluconazole; PDT was less effective than miconazole for oral candidiasis; Compared with nystatin alone, the combination of PDT and nystatin is more effective in treating oral candidiasis with less risk of recurrence.
Topics: Humans; Candidiasis, Oral; Antifungal Agents; Nystatin; Fluconazole; Miconazole; Photochemotherapy
PubMed: 37884914
DOI: 10.1186/s12903-023-03484-z -
International Journal of Molecular... Mar 2022Considering the challenges related to antimicrobial resistance, other strategies for controlling infections have been suggested, such as antimicrobial photodynamic... (Meta-Analysis)
Meta-Analysis Review
Considering the challenges related to antimicrobial resistance, other strategies for controlling infections have been suggested, such as antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides (AMP). This study aims to perform a systematic review and meta-analysis to obtain evidence on the antimicrobial effectiveness of aPDT associated with AMP and establish in vitro knowledge on this topic for further study designs. The PubMed, Scopus, Web of Science, Science Direct, Scielo, and Cochrane Library databases were searched. Two independent and calibrated researchers (Kappa = 0.88) performed all the systematic steps according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The odds ratio (OR) was used as the effect measure. The Peto method was used to perform the meta-analysis due to the sparse data. Twenty studies were included in the present review. The result was significant (OR = 0.14/ = 0.0235/I-squared = 0%), showing better outcomes of aPDT associated with peptides than those of aPDT alone for controlling the microbial load. Only 20% of the studies included evaluated this approach in a biofilm culture. Combined treatment with aPDT and AMP highly increased the ability of microbial reduction of Gram-positive and Gram-negative bacteria. However, additional blind studies are required to evaluate the efficacy of this therapy on microbial biofilms.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Peptides; Biofilms; Gram-Negative Bacteria; Gram-Positive Bacteria; Photochemotherapy; Photosensitizing Agents
PubMed: 35328647
DOI: 10.3390/ijms23063226 -
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