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Photochemical & Photobiological... May 2019Antimicrobial photodynamic therapy (aPDT) is a growing approach to treat skin and mucosal infections. Despite its effectiveness, investigators have explored whether aPDT...
BACKGROUND
Antimicrobial photodynamic therapy (aPDT) is a growing approach to treat skin and mucosal infections. Despite its effectiveness, investigators have explored whether aPDT can be further combined with antibiotics and antifungal drugs.
OBJECTIVE
To systematically assess the in vivo studies on the effectiveness of combinations of aPTD plus antimicrobials in the treatment of cutaneous and mucosal infections.
MATERIALS AND METHODS
Searches were performed in four databases (PubMed, EMBASE, Cochrane library databases, ClinicaTrials.gov) until July 2018. The pooled information was evaluated according to the PRISMA guidelines.
RESULTS
11 full-text articles were finally evaluated and included. The best aPDT combinations involved 5-aminolevulinic acid or phenothiazinium dye-based aPDT. In general, the combination shows benefits such as reducing treatment times, lowering drug dosages, decreasing drug toxicity, improving patient compliance and diminishing the risk of developing resistance. The mechanism of action may be that first aPDT damages the microbial cell wall or membrane, which allows better penetration of the antimicrobial drug.
LIMITATIONS
The number of studies was low, the protocols used were heterogeneous, and there was a lack of clinical trials.
CONCLUSIONS
The additive or synergistic effect of aPDT combined with antimicrobials could be promising to manage skin and mucosal infections, helping to overcome the microbial drug resistance.
Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Mouth Diseases; Mouth Mucosa; Photochemotherapy; Skin
PubMed: 30821303
DOI: 10.1039/c8pp00534f -
Dermatology Online Journal Nov 2018Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities. (Comparative Study)
Comparative Study
BACKGROUND
Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities.
OBJECTIVE
To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention.
METHODS
We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms: "cryotherapy", AND "basal cell carcinoma", OR "cryosurgery" OR "cryoablation" up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale.
RESULTS
Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage.
CONCLUSION
Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.
Topics: Carcinoma, Basal Cell; Cryosurgery; Dermatologic Surgical Procedures; Humans; Neoplasm Recurrence, Local; Photochemotherapy; Skin Neoplasms; Triethylenemelamine; Wound Healing
PubMed: 30695972
DOI: No ID Found -
Journal of Periodontology Jul 2018This systematic review evaluates the efficacy of antimicrobial photodynamic therapy (aPDT), as an adjunct to non-surgical or surgical therapy, on clinical and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review evaluates the efficacy of antimicrobial photodynamic therapy (aPDT), as an adjunct to non-surgical or surgical therapy, on clinical and patient-centered outcomes in patients with periodontitis or peri-implantitis.
METHODS
Randomized controlled trials (RCTs) with a follow-up duration ≥ 3 months that evaluated mechanical root/implant surface debridement (i.e., scaling and root planing [SRP] or implant surface scaling [ISS]) versus SRP or ISS plus aPDT for the treatment of adult patients (≥ 18 years old) with moderate-to-severe chronic (CP)/aggressive periodontitis (AgP) or peri-implantitis, respectively, were considered eligible for inclusion. The MEDLINE, EMBASE, and CENTRAL databases were searched for articles published up to and including March 2017. Random-effects meta-analyses were used throughout the review using continuous data (i.e., mean changes from baseline), and pooled estimates were expressed as weighted mean differences with their associated 95% confidence intervals. Additionally, summaries are presented of the included RCTs, critical remarks of the literature, and evidence quality rating/strength of recommendation of laser procedures.
RESULTS
Of 729 potentially eligible articles, 28 papers (26 studies) were included in the review. Individual study outcomes and four sets of meta-analysis showed potential statistical significant benefit of aPDT in improving clinical attachment level (CAL) (non-surgical treatment of AgP) and probing depth (PD) (non-surgical treatment of AgP and CP). However, the comparative differences in clinical outcomes were modest (< 1 mm), and the level of certainty for different therapies was considered low-to-moderate (i.e., more information would be necessary to allow for a reliable and definitive estimation of effect/magnitude of therapies on health outcomes). Overall, most of the strengths of clinical recommendations of aPDT were guided by the expert opinion.
CONCLUSIONS
aPDT may provide similar clinical improvements in PD and CAL when compared with conventional periodontal therapy for both periodontitis and peri-implantitis patients. The restricted base of evidence for some treatment approaches and conditions precludes additional conclusions.
Topics: Adolescent; Adult; Anti-Infective Agents; Dental Scaling; Humans; Peri-Implantitis; Photochemotherapy; Root Planing; United States
PubMed: 30133749
DOI: 10.1902/jop.2017.170172 -
Medicine May 2018We sought to conduct a systemic review and meta-analysis of randomized clinical trials to assess the efficacy and safety of photodynamic therapy (PDT) in cervical... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection: A systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
We sought to conduct a systemic review and meta-analysis of randomized clinical trials to assess the efficacy and safety of photodynamic therapy (PDT) in cervical intraepithelial neoplasia (CIN) and cervical human papilloma virus (HPV) infection.
METHODS
The Medline, EMBASE, and Cochrane Central Register databases were searched using relevant keywords for entries up to May 1, 2017, irrespective of year of publication. The language was restricted to English. Randomized clinical trials and qualitative studies comparing PDT and placebo for CIN or HPV-positive patients were included. We assessed the evidence quality using a risk of bias graph in RevMan V5.3 and the Grading of Recommendations Assessment, Development, and Evaluation scoring system.
RESULTS
Of the 168 studies identified, only 4 RCTs met the inclusion criteria for meta-analysis. In all, 292 and 141 patients received PDT or placebo, respectively. PDT significantly increased the complete remission rate (CRR) among those with CIN (odds ratio [OR]: 2.51 [1.23-5.12]; P = .01) and HPV infection (OR: 3.82 [1.91-7.65]; P = .0002). The adverse events rate (AER) for PDT was greater than that for placebo (OR: 13.32 [4.44, 40.02]; P < .00001). The overall evidence quality was very low. Similarly, in a systematic review including 21 qualitative records, the CRRs for CIN patients with PDT and cervical HPV infection patients with PDT were 82.0% and 77.5%, respectively. The AER for PDT was 31.6%, which was lower than that observed in our meta-analysis (74.6%).
CONCLUSIONS
PDT that targets CIN or cervical HPV infection improves the CRR, but slightly compromises safety. Further studies are necessary to identify the most effective and least toxic photosensitizer.
Topics: Adolescent; Adult; Female; Humans; Middle Aged; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Uterine Cervical Neoplasms; Young Adult; Uterine Cervical Dysplasia
PubMed: 29794788
DOI: 10.1097/MD.0000000000010864 -
The Cochrane Database of Systematic... Apr 2018Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular tumours are usually uncomplicated and tend to regress spontaneously. However, when haemangiomas occur in high-risk areas, such as near the eyes, throat, or nose, impairing their function, or when complications develop, intervention may be necessary. This is an update of a Cochrane Review first published in 2011.
OBJECTIVES
To assess the effects of interventions for the management of infantile haemangiomas in children.
SEARCH METHODS
We updated our searches of the following databases to February 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, LILACS, and CINAHL. We also searched five trials registries and checked the reference lists of included studies for further references to relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of all types of interventions, versus placebo, active monitoring, or other interventions, in any child with single or multiple infantile haemangiomas (IHs) located on the skin.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcome measures were clearance, a subjective measure of improvement, and adverse events. Secondary outcomes were other measures of resolution; proportion of parents or children who consider there is still a problem; aesthetic appearance; and requirement for surgical correction. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included 28 RCTs, with a total of 1728 participants, assessing 12 different interventions, including lasers, beta blockers (e.g. propranolol, timolol maleate), radiation therapy, and steroids. Comparators included placebo, an active monitoring approach, sham radiation, and interventions given alone or in combination.Studies were conducted in a number of countries, including China, Egypt, France, and Australia. Participant age ranged from 12 weeks to 13.4 years. Most studies (23/28) included a majority of females and different types of IHs. Duration of follow-up ranged from 7 days to 72 months.We considered most of the trials as at low risk of random sequence generation, attrition bias, and selective reporting bias. Domains such as allocation concealment and blinding were not clearly reported in general. We downgraded evidence for issues related to risk of bias and imprecision.We report results for the three most important comparisons, which we chose on the basis of current use. Outcome measurement of these comparisons was at 24 weeks' follow-up.Oral propranolol versus placeboCompared with placebo, oral propranolol 3 mg/kg/day probably improves clinician-assessed clearance (risk ratio (RR) 16.61, 95% confidence interval (CI) 4.22 to 65.34; 1 study; 156 children; moderate-quality evidence) and probably leads to a clinician-assessed reduction in mean haemangioma volume of 45.9% (95% CI 11.60 to 80.20; 1 study; 40 children; moderate-quality evidence). We found no evidence of a difference in terms of short- or long-term serious adverse events (RR 1.05, 95% CI 0.33 to 3.39; 3 studies; 509 children; low-quality evidence), nor in terms of bronchospasm, hypoglycaemia, or serious cardiovascular adverse events. The results relating to clearance and resolution for this comparison were based on one industry-sponsored study.Topical timolol maleate versus placeboThe chance of reduction of redness, as a measure of clinician-assessed resolution, may be improved with topical timolol maleate 0.5% gel applied twice daily when compared with placebo (RR 8.11, 95% CI 1.09 to 60.09; 1 study; 41 children;low-quality evidence). Regarding short- or long-term serious cardiovascular events, we found no instances of bradycardia (slower than normal heart rate) or hypotension in either group (1 study; 41 children; low-quality evidence). No other safety data were assessed, and clearance was not measured.Oral propranolol versus topical timolol maleateWhen topical timolol maleate (0.5% eye drops applied twice daily) was compared with oral propranolol (via a tablet taken once per day, at a 1.0 mg/kg dose), there was no evidence of a difference in haemangioma size (as a measure of resolution) when measured by the proportion of patients with a clinician-assessed reduction of 50% or greater (RR 1.13, 95% CI 0.64 to 1.97; 1 study; 26 participants; low-quality evidence). Although there were more short- or long-term general adverse effects (such as severe diarrhoea, lethargy, and loss of appetite) in the oral propranolol group, there was no evidence of a difference between groups (RR 7.00, 95% CI 0.40 to 123.35; 1 study; 26 participants; very low-quality evidence). This comparison did not measure clearance.None of our key comparisons evaluated, at any follow-up, a subjective measure of improvement assessed by the parent or child; proportion of parents or children who consider there is still a problem; or physician-, child-, or parent-assessed aesthetic appearance.
AUTHORS' CONCLUSIONS
We found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs.Our key results indicate that in the management of IH in children, oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harms. We found no evidence of a difference between oral propranolol and topical timolol maleate with regard to reducing haemangioma size, but we are uncertain if there is a difference in safety. Oral propranolol is currently the standard treatment for this condition, and our review has not found evidence to challenge this. However, these results are based on moderate- to very low-quality evidence.The included studies were limited by small sample sizes and risk of bias in some domains. Future trials should blind personnel and participants; describe trials thoroughly in publications; and recruit a sufficient number of children to deduce meaningful results. Future trials should assess patient-reported outcomes, as well as objective outcomes of benefit, and should report adverse events comprehensively. Propranolol and timolol maleate require further assessment in RCTs of all types of IH, including those considered problematic, as do other lesser-used interventions and new interventions. All treatments should be compared against propranolol and timolol maleate, as beta blockers are approved as standard care.
Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Antineoplastic Agents; Bleomycin; Child, Preschool; Hemangioma, Capillary; Humans; Infant; Lasers, Dye; Methylprednisolone; Photochemotherapy; Prednisolone; Propranolol; Radiotherapy; Randomized Controlled Trials as Topic; Remission Induction; Skin Neoplasms; Timolol
PubMed: 29667726
DOI: 10.1002/14651858.CD006545.pub3 -
The Cochrane Database of Systematic... Jan 2018Periodontitis is a bacterially-induced, chronic inflammatory disease that destroys the connective tissues and bone that support teeth. Active periodontal treatment aims... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is a bacterially-induced, chronic inflammatory disease that destroys the connective tissues and bone that support teeth. Active periodontal treatment aims to reduce the inflammatory response, primarily through eradication of bacterial deposits. Following completion of treatment and arrest of inflammation, supportive periodontal therapy (SPT) is employed to reduce the probability of re-infection and progression of the disease; to maintain teeth without pain, excessive mobility or persistent infection in the long term, and to prevent related oral diseases.According to the American Academy of Periodontology, SPT should include all components of a typical dental recall examination, and importantly should also include periodontal re-evaluation and risk assessment, supragingival and subgingival removal of bacterial plaque and calculus, and re-treatment of any sites showing recurrent or persistent disease. While the first four points might be expected to form part of the routine examination appointment for periodontally healthy patients, the inclusion of thorough periodontal evaluation, risk assessment and subsequent treatment - normally including mechanical debridement of any plaque or calculus deposits - differentiates SPT from routine care.Success of SPT has been reported in a number of long-term, retrospective studies. This review aimed to assess the evidence available from randomised controlled trials (RCTs).
OBJECTIVES
To determine the effects of supportive periodontal therapy (SPT) in the maintenance of the dentition of adults treated for periodontitis.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 5), MEDLINE Ovid (1946 to 8 May 2017), and Embase Ovid (1980 to 8 May 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating SPT versus monitoring only or alternative approaches to mechanical debridement; SPT alone versus SPT with adjunctive interventions; different approaches to or providers of SPT; and different time intervals for SPT delivery.We excluded split-mouth studies where we considered there could be a risk of contamination.Participants must have completed active periodontal therapy at least six months prior to randomisation and be enrolled in an SPT programme. Trials must have had a minimum follow-up period of 12 months.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results to identify studies for inclusion, assessed the risk of bias in included studies and extracted study data. When possible, we calculated mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables. Two review authors assessed the quality of evidence for each comparison and outcome using GRADE criteria.
MAIN RESULTS
We included four trials involving 307 participants aged 31 to 85 years, who had been previously treated for moderate to severe chronic periodontitis. Three studies compared adjuncts to mechanical debridement in SPT versus debridement only. The adjuncts were local antibiotics in two studies (one at high risk of bias and one at low risk) and photodynamic therapy in one study (at unclear risk of bias). One study at high risk of bias compared provision of SPT by a specialist versus general practitioner. We did not identify any RCTs evaluating the effects of SPT versus monitoring only, or of providing SPT at different time intervals, or that compared the effects of mechanical debridement using different approaches or technologies.No included trials measured our primary outcome 'tooth loss'; however, studies evaluated signs of inflammation and potential periodontal disease progression, including bleeding on probing (BoP), clinical attachment level (CAL) and probing pocket depth (PPD).There was no evidence of a difference between SPT delivered by a specialist versus a general practitioner for BoP or PPD at 12 months (very low-quality evidence). This study did not measure CAL or adverse events.Due to heterogeneous outcome reporting, it was not possible to combine data from the two studies comparing mechanical debridement with or without the use of adjunctive local antibiotics. Both studies found no evidence of a difference between groups at 12 months (low to very low-quality evidence). There were no adverse events in either study.The use of adjunctive photodynamic therapy did not demonstrate evidence of benefit compared to mechanical debridement only (very low-quality evidence). Adverse events were not measured.The quality of the evidence is low to very low for these comparisons. Future research is likely to change the findings, therefore the results should be interpreted with caution.
AUTHORS' CONCLUSIONS
Overall, there is insufficient evidence to determine the superiority of different protocols or adjunctive strategies to improve tooth maintenance during SPT. No trials evaluated SPT versus monitoring only. The evidence available for the comparisons evaluated is of low to very low quality, and hampered by dissimilarities in outcome reporting. More trials using uniform definitions and outcomes are required to address the objectives of this review.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chronic Periodontitis; Dental Plaque; Humans; Middle Aged; Periodontal Debridement; Periodontics; Photochemotherapy; Randomized Controlled Trials as Topic; Tooth Loss
PubMed: 29291254
DOI: 10.1002/14651858.CD009376.pub2 -
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 -
Biomolecules Nov 2017The aim of this systematic review was to investigate whether antimicrobial photodynamic therapy (aPDT) as either a primary mode of treatment or an adjunct to... (Review)
Review
The aim of this systematic review was to investigate whether antimicrobial photodynamic therapy (aPDT) as either a primary mode of treatment or an adjunct to non-surgical treatment was more effective than scaling and root planing (SRP) alone in treating chronic periodontitis in terms of clinical attachment level (CAL) gain and probing depth (PD) reduction. The focused question was developed using the Patient, Intervention, Comparison, and Outcome (PICO) format, and two authors independently searched the Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies from January 2008 to December 2016. Twenty studies included in this systematic review were randomized clinical trials (RCTs) or quasi-RCTs of aPDT compared to placebo, no intervention, or non-surgical treatment in an adult population. Basic study characteristics, photosensitizing agents and wavelengths used in aPDT, frequency of aPDT application, effect of aPDT on clinical parameters, antimicrobial effect of aPDT in chronic periodontitis, effect of immunological parameters following aPDT and patient-based outcome measures were collected from the studies. Although there was a wide range of heterogeneity in the included studied, they all indicated that aPDT has the potential to be an effective adjunct in the treatment of chronic periodontitis. Long-term, multicenter studies with larger sample sizes are needed before aPDT can be recommended as an effective treatment modality.
Topics: Anti-Infective Agents; Chronic Periodontitis; Dental Scaling; Humans; Photochemotherapy; Photosensitizing Agents; Root Planing
PubMed: 29186805
DOI: 10.3390/biom7040079 -
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 -
Photodiagnosis and Photodynamic Therapy Dec 2017Peritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although... (Review)
Review
BACKGROUND
Peritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis.
METHODS
We systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017).
RESULTS
Three human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15-300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0-4 [4=highest]: PDT 3.4±1.0 vs. control 0.4±0.6, p<0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p<0.001).
CONCLUSION
PDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.
Topics: Animals; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Humans; Peritoneal Neoplasms; Photochemotherapy; Photosensitizing Agents; Prognosis
PubMed: 29111390
DOI: 10.1016/j.pdpdt.2017.10.021