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Wound Repair and Regeneration :... Jan 2021Pathological scars can result in functional impairment, disfigurement, a psychological burden, itch, and even chronic pain. We conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
Pathological scars can result in functional impairment, disfigurement, a psychological burden, itch, and even chronic pain. We conducted a systematic review to investigate the influence of incisional Negative Pressure Wound Therapy (iNPWT) on scarring. PubMed, EMBASE and CINAHL were searched for preclinical and clinical comparative studies that investigated the influence of iNPWT on scarring-related outcomes. Individual studies were assessed using the OHAT Risk of Bias Rating Tool for Human and Animal studies. The body of evidence was rated using OHAT methodology. Six preclinical studies and nine clinical studies (377 patients) were identified. Preclinical studies suggested that iNPWT reduced lateral tension on incisions, increased wound strength, and reduced scar width upon histological assessment. Two clinical studies reported improved patient-reported scar satisfaction as measured with the PSAS (1 year after surgery), POSAS, and a VAS (both 42, 90, and 180 days after surgery). Five clinical studies reported improved observer-reported scar satisfaction as measured with the VSS, SBSES, OSAS, MSS, VAS, and POSAS (7, 15, 30, 42, 90, 180, and 365 days after surgery). Three clinical studies did not detect significant differences at any point in time (POSAS, VAS, and NRS). Because of imprecision concerns, a moderate level of evidence was identified using OHAT methodology. Preclinical as well as clinical evidence indicates a beneficial influence of iNPWT on scarring. Moderate level evidence indicates that iNPWT decreases scar width and improves patient and observer-reported scar satisfaction.
Topics: Animals; Cicatrix; Humans; Negative-Pressure Wound Therapy; Surgical Wound Infection; Wound Healing
PubMed: 32789902
DOI: 10.1111/wrr.12858 -
Indian Journal of Plastic Surgery :... Mar 2020Chronic tenosynovitis of the upper extremities caused by ( ) is uncommon, but symptoms may overlap with other more common diseases. Late diagnosis and treatment... (Review)
Review
Chronic tenosynovitis of the upper extremities caused by ( ) is uncommon, but symptoms may overlap with other more common diseases. Late diagnosis and treatment can lead to disfiguration of structures and rupture of tendons, resulting in worse cosmetic outcomes after reconstruction. We present a clinical case and literature review of in patients with chronic tenosynovitis of upper extremities. PubMed was queried for cases of upper extremities tenosynovitis caused by . The keywords " ," "tenosynovitis" and synonyms were used for search in different combinations. Manuscripts, with no specific data or another condition, where the infection was not located in the upper extremities, were reviews, or not in English, were excluded from the study. We described 23 reported cases of tenosynovitis of the upper extremity caused by . An immunosuppressed state was present in eight (34.8%) cases, and 12 (52.2%) patients received immunosuppressive treatment. A long-time period between the first appearance of symptoms and the definitive diagnosis was identified (median: 7 months, interquartile range: 9). The most frequent symptoms were local swelling (65.2%), pain (56.5%), mass effect (26%), and stiffness (13%). Tendon rupture was found in three (13%) patients as a complication of the disease. Moreover, seven (30.4%) patients underwent previous surgeries to try to relieve the symptoms before definitive diagnosis was achieved. is an important differential causal pathogen for tenosynovitis of the upper extremities. Although rare, raising awareness about this infectious disease is imperative to avoid inadequate management and hazardous aesthetic sequelae.
PubMed: 32367915
DOI: 10.1055/s-0040-1709377 -
The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
Plastic and Reconstructive Surgery.... Oct 2019Currently, there are more than 40 cases of facial allotransplantation performed by 13 different groups in 10 countries. Although it has become a potential option to...
BACKGROUND
Currently, there are more than 40 cases of facial allotransplantation performed by 13 different groups in 10 countries. Although it has become a potential option to reconstruct and restore the function and appearance of severely facially disfigured individuals, the ethical concerns of facial allotransplantation remain unsolved. We conducted a systematic review to better understand the ethical concerns on facial allotransplantation and the changing trends of the ethical debate over time.
METHODS
A systematic review of 3 databases was performed to identify articles related to ethical topics on facial allotransplantation. The inclusion criteria were peer-reviewed articles written since 1995 on the topics of ethics and facial allotransplantation in English, French, and Chinese languages. The ethical concerns extracted from the included articles were categorized into 4 core principles of ethics: autonomy, beneficence, nonmaleficence, and justice. The different themes under these 4 principles were extracted and subgrouped. The positions of the included articles were collected. Joinpoint regression was applied to compare the frequency of themes and positions by publication year. We presented the main topics on ethical concerns and the changing trends in ethical themes and principles of facial allotransplantation.
RESULTS
There were 889 articles identified initially. After excluding 265 duplicated articles, 624 articles were included for title/abstract review process, and 148 articles were included in final data analysis. The publication year was from 2002 to 2018 with 136 articles in English, 11 in French, and 1 in Chinese. The most addressed principle was nonmaleficence (117/148, 79.1%), followed by beneficence (116/148, 78.4%), justice (103/148, 69.6%), and autonomy (86/148, 58.1%). The themes on immunosuppression/rejection, quality of life, and identity were the top 3 addressed ethical concerns. Twelve of 13 most addressed ethical themes demonstrated a decreasing trend after 2004. The themes of identity under beneficence showed a significant decrease after 2004. Ethical concerns on the cost/financial topic were the only one showing consistently increase trends from 2002 to 2018. There was a significant increase of the papers in favor of facial allotransplantation procedure comparing to those were against or neutral before and after 2008.
CONCLUSIONS
More and more articles support facial allotransplantation as a feasible option to reconstruct and restore the function and appearance of severely facially disfigured individuals. The requirement of life-long immunosuppression therapy, quality of life, and identity center the ethical debates. Supported by favorable short-term results, 12 of 13 most addressed ethical concerns have trended down. The theme of cost/financial topic becomes more frequently addressed in recent years.
PubMed: 31772878
DOI: 10.1097/GOX.0000000000002425 -
Neuro-oncology Practice Nov 2018Body image dissatisfaction is a common issue among patients with cancer and is associated with difficulty coping, anxiety, and depression. Patients with tumors involving... (Review)
Review
Body image dissatisfaction is a common issue among patients with cancer and is associated with difficulty coping, anxiety, and depression. Patients with tumors involving the head and neck are at increased risk of body image dissatisfaction due to the visible disfigurement that can occur from their illness and its treatment. Patients with primary central nervous system (CNS) malignancies often face similar tumor-related and treatment-related effects, yet there is limited research conducted in this population. Our aim was to perform a systematic review of the literature on body image in patients with tumors of the head and neck, and identify factors associated with body image alterations during treatment, with the intention of applying these approaches to those with CNS disease. A systematic search of PubMed and EMBASE was performed using predefined criteria. Nine studies met the inclusion criteria and were selected for review. The literature collected showed a relationship between body image and age, depressive symptoms, and tumor grade or stage. In addition, body image disturbance had an impact on patients' daily functioning and psychosocial indices including anxiety, coping, and body reintegration. Evaluation of the impact of body image alterations in patients with CNS tumors is needed to direct clinical care, explore research opportunities, and improve patient quality of life.
PubMed: 31386002
DOI: 10.1093/nop/npy018 -
The Lancet. Global Health Jul 2019Buruli ulcer can cause disfigurement and long-term loss of function. It is underdiagnosed and under-reported, and its current distribution is unclear. We aimed to...
BACKGROUND
Buruli ulcer can cause disfigurement and long-term loss of function. It is underdiagnosed and under-reported, and its current distribution is unclear. We aimed to synthesise and evaluate data on Buruli ulcer prevalence and distribution.
METHODS
We did a systematic review of Buruli ulcer prevalence and used an evidence consensus framework to describe and evaluate evidence for Buruli ulcer distribution worldwide. We searched PubMed and Web of Science databases from inception to Aug 6, 2018, for records of Buruli ulcer and Mycobacterium ulcerans detection, with no limits on study type, publication date, participant population, or location. English, French, and Spanish language publications were included. We included population-based surveys presenting Buruli ulcer prevalence estimates, or data that allowed prevalence to be estimated, in the systematic review. We extracted geographical data on the occurrence of Buruli ulcer cases and M ulcerans detection from studies of any type for the evidence consensus framework; articles that did not report original data were excluded. For the main analysis, we extracted prevalence estimates from included surveys and calculated 95% CIs using Byar's method. We included occurrence records, reports to WHO and the Global Infectious Diseases and Epidemiology Network, and surveillance data from Buruli ulcer control programmes in the evidence consensus framework to grade the strength of evidence for Buruli ulcer endemicity. This study is registered with PROSPERO, number CRD42018116260.
FINDINGS
2763 titles met the search criteria. We extracted prevalence estimates from ten studies and occurrence data from 208 studies and five unpublished surveillance datasets. Prevalence estimates within study areas ranged from 3·2 (95% CI 3·1-3·3) cases per 10 000 population in Côte d'Ivoire to 26·9 (23·5-30·7) cases per 10 000 population in Benin. There was evidence of Buruli ulcer in 32 countries and consensus on presence in 12.
INTERPRETATION
The global distribution of Buruli ulcer is uncertain and potentially wider than currently recognised. Our findings represent the strongest available evidence on Buruli ulcer distribution so far and have many potential applications, from directing surveillance activities to informing burden estimates.
FUNDING
AIM Initiative.
Topics: Buruli Ulcer; Geographic Mapping; Global Health; Humans; Mycobacterium ulcerans; Prevalence
PubMed: 31200890
DOI: 10.1016/S2214-109X(19)30171-8 -
The Cochrane Database of Systematic... May 2019Orbital lymphangiomas are a subset of localized vascular and lymphatic malformations, which most commonly occur in the head and neck region. Orbital lymphangiomas...
BACKGROUND
Orbital lymphangiomas are a subset of localized vascular and lymphatic malformations, which most commonly occur in the head and neck region. Orbital lymphangiomas typically present in the first decade of life with signs of ptosis, proptosis, restriction of ocular motility, compressive optic neuropathy, and disfigurement. Therefore, early and effective treatment is crucial to preserving vision. Due to proximity to vital structures, such as the globe, optic nerve, and extraocular muscles, treatment for these lesions is complicated and includes a large array of approaches including observation, sclerotherapy, systemic therapy, and surgical excision. Of these options, there is no clear gold standard of treatment.
OBJECTIVES
To assess the evidence supporting medical and surgical interventions for the reduction/treatment of orbital lymphangiomas in children and young adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 5); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 May 2018.
SELECTION CRITERIA
We planned to include randomized controlled trials (RCTs) comparing at least two of the following interventions with each other for the treatment of orbital lymphangiomas: observation; sildenafil therapy; sirolimus therapy; sclerotherapy; surgery (partial or complete resection). We planned to include trials that enrolled children and adults up to 32 years of age, based on a prior clinical trial protocol. There were no restrictions regarding location or demographic factors.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles, abstracts, and full articles to assess their suitability for inclusion in this review. No risk of bias or data extraction was performed because we did not find any trials for inclusion. If there had been RCTs, two authors would have assessed the risk of bias and abstracted data independently with discrepancies being settled by consensus or consultation with a third review author.
MAIN RESULTS
There were no RCTs that compared any two of the mentioned interventions (medical or surgical) for treating orbital lymphangiomas in children and young adults.
AUTHORS' CONCLUSIONS
Currently, there are no published RCTs of orbital lymphangioma treatments. Without these types of studies, conclusions cannot be drawn regarding the effectiveness of the medical and surgical treatment options for patients with orbital lymphangiomas. The presence of only case reports and case series on orbital lymphangiomas makes it clear that RCTs are needed to address the differences between these options and help guide treatment plans. Such trials would ideally compare outcomes between individuals randomized to one of the following treatment options: observation, sclerotherapy, systemic sirolimus therapy, systemic sildenafil therapy, and surgical excision.
Topics: Antibiotics, Antineoplastic; Humans; Lymphangioma; Orbital Neoplasms; Treatment Outcome
PubMed: 31094450
DOI: 10.1002/14651858.CD013000.pub2 -
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 -
Tropical Medicine and Infectious Disease May 2018is the causative agent of Buruli ulcer, also known in Australia as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and... (Review)
Review
is the causative agent of Buruli ulcer, also known in Australia as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and painless necrosis of the skin and soft tissue with the formation of large ulcers, commonly on the leg or arm. To date, 33 countries with tropical, subtropical and temperate climates in Africa, the Americas, Asia and the Western Pacific have reported cases of Buruli ulcer. The disease is rarely fatal, although it may lead to permanent disability and/or disfigurement if not treated appropriately or in time. It is the third most common mycobacterial infection in the world after tuberculosis and leprosy. The precise mode of transmission of is yet to be elucidated. Nevertheless, it is possible that the mode of transmission varies with different geographical areas and epidemiological settings. The knowledge about the possible routes of transmission and potential animal reservoirs of is poorly understood and still remains patchy. Infectious diseases arise from the interaction of agent, host and environment. The majority of emerging or remerging infectious disease in human populations is spread by animals: either wildlife, livestock or pets. Animals may act as hosts or reservoirs and subsequently spread the organism to the environment or directly to the human population. The reservoirs may or may not be the direct source of infection for the hosts; however, they play a major role in maintenance of the organism in the environment, and in the mode of transmission. This remains valid for . Possums have been suggested as one of the reservoir of in south-eastern Australia, where possums ingest from the environment, amplify them and shed the organism through their faeces. We conducted a systematic review with selected key words on PubMed and INFORMIT databases to aggregate available published data on animal reservoirs of around the world. After certain inclusion and exclusion criteria were implemented, a total of 17 studies was included in the review. A variety of animals around the world e.g., rodents, shrews, possums (ringtail and brushtail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have been recorded as being infected with . The majority of studies included in this review identified animal reservoirs as predisposing to the emergence and reemergence of infection. Taken together, from the selected studies in this systematic review, it is clear that exotic wildlife and native mammals play a significant role as reservoirs for
PubMed: 30274452
DOI: 10.3390/tropicalmed3020056 -
The Cochrane Database of Systematic... Aug 2018Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery.
OBJECTIVES
To summarize the evidence of drug treatments for treating Buruli ulcer.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.Rifampicin combined with streptomycinWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).An additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.Rifampicin combined with clarithromycinTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phaseOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).Novel combination therapyTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%.
AUTHORS' CONCLUSIONS
While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.
Topics: Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Clofazimine; Drug Therapy, Combination; Humans; Mycobacterium ulcerans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Rifampin; Streptomycin; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30136733
DOI: 10.1002/14651858.CD012118.pub2