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The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
European Journal of Medicinal Chemistry Aug 2020The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections in both the community and healthcare settings...
Contemporary approaches and future perspectives of antibacterial photodynamic therapy (aPDT) against methicillin-resistant Staphylococcus aureus (MRSA): A systematic review.
The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections in both the community and healthcare settings challenges the limited options of effective antibiotics and motivates the search for alternative therapeutic solutions, such as antibacterial photodynamic therapy (aPDT). While many publications have described the promising anti-bacterial activities of PDT in vitro, its applications in vivo and in the clinic have been very limited. This limited availability may in part be due to variabilities in the selected photosensitizing agents (PS), the variable testing conditions used to examine anti-bacterial activities and their effectiveness in treating MRSA infections. We thus sought to systematically review and examine the evidence from existing studies on aPDT associated with MRSA and to critically appraise its current state of development and areas to be addressed in future studies. In 2018, we developed and registered a review protocol in the International Prospective Register of Systematic Reviews (PROSPERO) with registration No: CRD42018086736. Three bibliographical databases were consulted (PUBMED, MEDLINE, and EMBASE), and a total of 113 studies were included in this systematic review based on our eligibility criteria. Many variables, such as the use of a wide range of solvents, pre-irradiation times, irradiation times, light sources and light doses, have been used in the methods reported by researchers, which significantly affect the inter-study comparability and results. On another note, new approaches of linking immunoglobulin G (IgG), antibodies, efflux pump inhibitors, and bacteriophages with photosensitizers (PSs) and the incorporation of PSs into nano-scale delivery systems exert a direct effect on improving aPDT. Enhanced activities have also been achieved by optimizing the physicochemical properties of the PSs, such as the introduction of highly lipophilic, poly-cationic and site-specific modifications of the compounds. However, few in vivo studies (n = 17) have been conducted to translate aPDT into preclinical studies. We anticipate that further standardization of the experimental conditions and assessing the efficacy in vivo would allow this technology to be further applied in preclinical trials, so that aPDT would develop to become a sustainable, alternative therapeutic option against MRSA infection in the future.
Topics: Antibodies, Bacterial; Drug Delivery Systems; Humans; Methicillin-Resistant Staphylococcus aureus; Photochemotherapy; Photosensitizing Agents; Staphylococcal Infections
PubMed: 32505848
DOI: 10.1016/j.ejmech.2020.112341 -
Journal of Clinical Periodontology Jul 2020To compare the adjunctive effects of lasers or antimicrobial photodynamic therapy (aPDT) to non-surgical mechanical instrumentation alone in untreated periodontitis... (Meta-Analysis)
Meta-Analysis Review
Adjunctive laser or antimicrobial photodynamic therapy to non-surgical mechanical instrumentation in patients with untreated periodontitis: A systematic review and meta-analysis.
AIM
To compare the adjunctive effects of lasers or antimicrobial photodynamic therapy (aPDT) to non-surgical mechanical instrumentation alone in untreated periodontitis patients.
MATERIALS AND METHODS
Two focused questions were addressed using the Population, Intervention, Comparison and Outcome criteria as follows: in patients with untreated periodontitis, (a) does laser application provide adjunctive effects on probing pocket depth (PPD) changes compared with non-surgical instrumentation alone? and (b) does application of aPDT provide adjunctive effects on PPD changes compared with non-surgical instrumentation alone? Both randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) were included. Results of the meta-analysis are expressed as weighted mean differences (WMD) and reported according to the PRISMA guidelines.
RESULTS
Out of 1,202 records, 10 articles for adjunctive laser and 8 for adjunctive aPDT were included. With respect to PPD changes, 1 meta-analysis including 2 articles (total n = 42; split-mouth design) failed to identify a statistically significant difference (WMD = 0.35 mm; 95%CI: -0.04/0.73; p = .08) in favour of adjunctive aPDT (wavelength range 650-700 nm). In terms of adjunctive laser application, a high variability of clinical outcomes at 6 months was noted. Two articles included patient-reported outcomes and 10 reported on the presence/absence of harms/adverse effects.
CONCLUSIONS
Available evidence on adjunctive therapy with lasers and aPDT is limited by (a) the low number of controlled studies and (b) the heterogeneity of study designs. Patient-reported benefits remain to be demonstrated.
Topics: Anti-Infective Agents; Chronic Periodontitis; Dental Scaling; Humans; Lasers; Photochemotherapy; Root Planing
PubMed: 31859395
DOI: 10.1111/jcpe.13236 -
International Wound Journal Apr 2020Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently...
Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.
Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Methicillin-Resistant Staphylococcus aureus; Photochemotherapy; Soft Tissue Injuries; Staphylococcal Infections; Wound Healing; Wound Infection
PubMed: 31724831
DOI: 10.1111/iwj.13269 -
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 Aug 2019Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice.
METHODS
We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias.
RESULTS
Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI - 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11).
CONCLUSION
The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.
Topics: Anti-Bacterial Agents; Bayes Theorem; Blood Glucose; Chronic Periodontitis; Combined Modality Therapy; Dental Scaling; Diabetes Mellitus, Type 2; Doxycycline; Female; Humans; Male; Network Meta-Analysis; Periodontal Pocket; Photochemotherapy; Randomized Controlled Trials as Topic; Root Planing; Treatment Outcome
PubMed: 31387569
DOI: 10.1186/s12903-019-0829-y -
International Journal of Molecular... Jul 2019The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.
Topics: Bacteroidaceae Infections; Biofilms; Candida; Candidiasis; Curcumin; Dental Caries; Humans; Methylene Blue; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Rosaniline Dyes; Streptococcal Infections; Streptococcus; Tolonium Chloride; Treatment Outcome
PubMed: 31340425
DOI: 10.3390/ijms20143585 -
Phytomedicine : International Journal... Jul 2019Photoactivity, though known for centuries, is only recently shifting back into focus as a treatment option against cancer and microbial infections. The external factor...
BACKGROUND
Photoactivity, though known for centuries, is only recently shifting back into focus as a treatment option against cancer and microbial infections. The external factor light is the ingenious key-component of this therapy: Since light activates the drug locally, a high level of selectivity is reached and side effects are avoided. The first reported photoactive medicines were plant extracts. Synthetic entities (so-called photosensitizers PSs), however, paved the route towards the clinical approval of the so-called photodynamic therapy (PDT), and thus natural PSs took a backseat in the past.
HYPOTHESIS
Many isolated bioactive phytochemicals hold a hidden photoactive potential, which is overlooked due to the reduced common awareness of photoactivity.
METHODS
A systematic review of reported natural PSs and their supposed medicinal application was conducted by employing PubMed, Scifinder, and Web of Science. The identified photoactive natural products were compiled including information about their natural sources, their photoyield, and their pharmacological application. Furthermore, the common chemical scaffolds of natural PS are shown to enable the reader to recognize potentially overlooked natural PSs.
RESULTS
The literature review revealed over 100 natural PS, excluding porphyrins. The PSs were classified according to their scaffold. Thereby it was shown that some PS-scaffolds were analyzed in a detailed way, while other classes were only scarcely investigated, which leaves space for future discoveries. In addition, the literature revealed that many PSs are phytoalexins, thus the selection of the starting material significantly matters in order to find new PSs.
CONCLUSION
Photoactive principles are ubiquitous and can be found in various plant extracts. With the increasing availability of light-irradiation setups for the identification of photoactive natural products, we anticipate the discovery of many new natural PSs in the near future. With the accumulation of chemically diverse PSs, PDT itself might finally reach its clinical breakthrough as a promising alternative treatment against multi-resistant microbes and cancer types.
Topics: Biological Products; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Sesquiterpenes; Phytoalexins
PubMed: 31257117
DOI: 10.1016/j.phymed.2019.152985 -
The Cochrane Database of Systematic... Jun 2019This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most...
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery.
OBJECTIVES
To evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva, DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data.
MAIN RESULTS
The search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.This update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women.
AUTHORS' CONCLUSIONS
Since the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Humans; Imiquimod; Laser Therapy; Middle Aged; Paget Disease, Extramammary; Photochemotherapy; Randomized Controlled Trials as Topic; Vulvar Neoplasms
PubMed: 31167037
DOI: 10.1002/14651858.CD009245.pub3 -
International Journal of Oral Science Apr 2019With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth...
With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature. Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
Topics: Aminolevulinic Acid; Humans; Leukoplakia, Oral; Photochemotherapy; Photosensitizing Agents; Practice Guidelines as Topic
PubMed: 30971683
DOI: 10.1038/s41368-019-0047-0