Comparative assessment of interventions for treating cutaneous leishmaniasis: A network meta-analysis of randomized clinical trials.

INTRODUCTION: Various interventions including laser therapy, heat therapy, and several drugs have been trialed in patients with cutaneous leishmaniasis. Due to the lack of an evidence-based comparison of all these interventions, we carried out the present network meta-analysis. METHODS: Electronic databases were searched for randomized clinical trials evaluating the efficacy and safety of any interventions in patients with cutaneous leishmaniasis. The proportion of patients with complete cure was the primary outcome. The proportion of lesions cured at the end of treatment, the proportion of lesions with minimal/no response to treatment, and proportion of wounds with minimal/no change were the secondary outcomes. Random-effects modeling was used for generating pooled estimates. Rankogram plot was used for identifying the 'best intervention'. For interventions containing a combination of treatments, backslash (/) has been used for depicting the same. RESULTS: One-hundred and thirty-one studies were included. Intralesional meglumine, topical paromomycin/gentamicin, topical paromomycin, parenteral sodium stibogluconate, topical honey/intralesional meglumine, topical liposomal amphotericin B, oral zinc sulphate, oral miltefosine, parenteral meglumine, heat therapy, topical liposomal azithromycin, intralesional meglumine/silver dressing, intralesional sodium stibogluconate, parenteral meglumine/intralesional meglumine, oral allopurinol/parenteral meglumine, topical trichloroacetic acid/heat therapy, oral zinc sulphate/oral ketoconazole, topical imiquimod/cryotherapy, intralesional meglumine/cryotherapy, topical herbal extract of Z-HE, parenteral pentamidine, topical trichloroacetic acid/intralesional meglumine, carbon-dioxide laser, topical recombinant granulocyte-macrophage colony-stimulating factor/parenteral meglumine, intralesional dapsone, carbon-dioxide laser/intralesional meglumine, moist wet dressing with sodium hypochlorite, parenteral sodium stibogluconate/intralesional recombinant granulocyte-macrophage colony-stimulating factor, oral dapsone, intralesional sodium stibogluconate/oral ketoconazole, intralesional sodium stibogluconate/parenteral sodium stibogluconate and electrocautery/moist wet dressing with sodium hypochlorite were observed with significantly greater proportion of patients with complete cure compared to placebo/untreated controls. Rankogram analysis revealed that parenteral pentamidine has the highest statistical probability of being the best in the pool. CONCLUSION: We observed several interventions to be effective for treating cutaneous leishmaniasis. However, greater caution is required in interpreting the results as the estimates are likely to change with the advent of results from future studies.

Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.

BACKGROUND: Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. OBJECTIVES: To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. MAIN RESULTS: We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). AUTHORS' CONCLUSIONS: We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.

Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials.

AIMS: Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. METHODS: Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio (95% confidence interval) was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of lower limb amputation compared to standard of care. CONCLUSION: To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

Tranexamic acid in total hip arthroplasty: A recursive cumulative meta-analysis of randomized controlled trials and assessment of publication bias.

INTRODUCTION: TXA has been evaluated in THA in several randomized controlled trials for the past 16 years. We attempted to evaluate the trends in the evidence using recursive cumulative meta-analysis and publication bias using Rosenthal and 'Trim and Fill' methods. METHODS: Electronic databases were searched for randomized controlled clinical trials comparing TXA with either placebo (or no TXA administration) or TXA, administered through different routes in patients with osteoarthritis or osteonecrosis of the hip who underwent THA. We considered the total number of patients requiring blood transfusion as the clinical outcome for both the analyses and used quality effects model for assessing the changes in the pooled estimates with addition of new clinical trial data. We also assessed the publication bias by plotting individual study estimates with the standard errors using Rosenthal and 'Trim and Fill'methods. RESULTS: A total of 20 studies were included. The pooled cumulative meta-analysis indicates that from 2014 the addition of estimate from new studies in the following years is only narrowing the confidence interval without any significant change in the point estimate. Rosenthal fail-safe-N for the comparisons of intravenous bolus TXA, intra-operative and post-operative intravenous TXA and topical with control groups were 54, 6 and 16 respectively. Fail-safe-N for the combined intravenous and topical TXA with intravenous TXA alone was 13. CONCLUSION: Adequate evidence exists supporting the use of intravenous TXA in reducing the need for blood transfusion in THA. There is possible existence of small studies with null effects evaluating the use of TXA in THA.