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Background: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America., Methods: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact., Results: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care., Conclusions: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes., Lay Summary: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

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., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of thromboembolism. Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of thromboembolism after ICH, but they may increase the risks of bleeding., Objectives: To determine the overall effectiveness and safety of antithrombotic drugs for people with ICH., Search Methods: We searched the Cochrane Stroke Group Trials Register (24 March 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library 2017, Issue 3), MEDLINE Ovid (from 1948 to March 2017), Embase Ovid (from 1980 to March 2017), and online registries of clinical trials (8 March 2017). We also screened the reference lists of included trials for additional, potentially relevant studies., Selection Criteria: We selected all randomised controlled trials (RCTs) of any antithrombotic treatment after ICH., Data Collection and Analysis: Three review authors independently extracted data. We converted categorical estimates of effect to the risk ratio (RR) or odds ratio (OR), as appropriate. We divided our analyses into short- and long-term treatment, and used fixed-effect modelling for meta-analyses. Three review authors independently assessed the included RCTs for risks of bias and we created a 'Summary of findings' table using GRADE., Main Results: We included two RCTs with a total of 121 participants. Both RCTs were of short-term parenteral anticoagulation early after ICH: one tested heparin and the other enoxaparin. The risk of bias in the included RCTs was generally unclear or low, with the exception of blinding of participants and personnel, which was not done. The included RCTs did not report our chosen primary outcome (a composite outcome of all serious vascular events including ischaemic stroke, myocardial infarction, other major ischaemic event, ICH, major extracerebral haemorrhage, and vascular death). Parenteral anticoagulation did not cause a statistically significant difference in case fatality (RR 1.25, 95% confidence interval (CI) 0.38 to 4.07 in one RCT involving 46 participants, low-quality evidence), ICH, or major extracerebral haemorrhage (no detected events in one RCT involving 75 participants, low-quality evidence), growth of ICH (RR 1.64, 95% CI 0.51 to 5.29 in two RCTs involving 121 participants, low-quality evidence), deep vein thrombosis (RR 0.99, 95% CI 0.49 to 1.96 in two RCTs involving 121 participants, low quality evidence), or major ischaemic events (RR 0.54, 95% CI 0.23 to 1.28 in two RCTs involving 121 participants, low quality evidence)., Authors' Conclusions: There is insufficient evidence from RCTs to support or discourage the use of antithrombotic treatment after ICH. RCTs comparing starting versus avoiding antiplatelet or anticoagulant drugs after ICH appear justified and are needed in clinical practice.

Background: Actinic keratoses are a skin disease caused by long-term sun exposure, and their lesions have the potential to develop into squamous cell carcinoma. Treatments for actinic keratoses are sought for cosmetic reasons, for the relief of associated symptoms, or for the prevention of skin cancer development. Detectable lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present. The interventions available for the treatment of actinic keratoses include individual lesion-based (e.g. cryotherapy) or field-directed (e.g. topical) treatments. These might vary in terms of efficacy, safety, and cosmetic outcomes., Objectives: To assess the effects of topical, oral, mechanical, and chemical interventions for actinic keratosis., Search Methods: We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also searched trials registers, conference proceedings, and grey literature sources., Selection Criteria: Randomised controlled trials (RCTs) comparing the treatment of actinic keratoses with either placebo, vehicle, or another active therapy., Data Collection and Analysis: At least two authors independently abstracted data, which included adverse events, and assessed the quality of evidence. We performed meta-analysis to calculate a weighted treatment effect across trials, and we expressed the results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes (e.g. participant complete clearance rates), and mean difference (MD) and 95% CI for continuous outcomes (e.g. mean reduction in lesion counts)., Main Results: We included 83 RCTs in this review, with a total of 10,036 participants. The RCTs covered 18 topical treatments, 1 oral treatment, 2 mechanical interventions, and 3 chemical interventions, including photodynamic therapy (PDT). Most of the studies lacked descriptions of some methodological details, such as the generation of the randomisation sequence or allocation concealment, and half of the studies had a high risk of reporting bias. Study comparison was difficult because of the multiple parameters used to report efficacy and safety outcomes, as well as statistical limitations. We found no data on the possible reduction of squamous cell carcinoma.The primary outcome 'participant complete clearance' significantly favoured four field-directed treatments compared to vehicle or placebo: 3% diclofenac in 2.5% hyaluronic acid (RR 2.46, 95% CI 1.66 to 3.66; 3 studies with 420 participants), 0.5% 5-fluorouracil (RR 8.86, 95% CI: 3.67 to 21.44; 3 studies with 522 participants), 5% imiquimod (RR 7.70, 95% CI 4.63 to 12.79; 9 studies with1871 participants), and 0.025% to 0.05% ingenol mebutate (RR 4.50, 95% CI 2.61 to 7.74; 2 studies with 456 participants).It also significantly favoured the treatment of individual lesions with photodynamic therapy (PDT) compared to placebo-PDT with the following photosensitisers: aminolevulinic acid (ALA) (blue light: RR 6.22, 95% CI 2.88 to 13.43; 1 study with 243 participants, aminolevulinic acid (ALA) (red light: RR 5.94, 95% CI 3.35 to 10.54; 3 studies with 422 participants), and methyl aminolevulinate (MAL) (red light: RR 4.46, 95% CI 3.17 to 6.28; 5 studies with 482 participants). ALA-PDT was also significantly favoured compared to cryotherapy (RR 1.31, 95% CI 1.05 to 1.64).The corresponding comparative risks in terms of number of participants completely cleared per 1000 were as follows: 313 with 3% diclofenac compared to 127 with 2.5% hyaluronic acid; 136 with 0.5% 5-fluorouracil compared to 15 with placebo; 371 with 5% imiquimod compared to 48 with placebo; 331 with ingenol mebutate compared to 73 with vehicle; 527 to 656 with ALA/MAL-PDT treatment compared to 89 to 147 for placebo-PDT; and 580 with ALA-PDT compared to 443 with cryotherapy.5% 5-fluorouracil efficacy was not compared to placebo, but it was comparable to 5% imiquimod (RR 1.85, 95% Cl 0.41 to 8.33).A significant number of participants withdrew because of adverse events with 144 participants affected out of 1000 taking 3% diclofenac in 2.5% hyaluronic acid, compared to 40 participants affected out of 1000 taking 2.5% hyaluronic acid alone, and 56 participants affected out of 1000 taking 5% imiquimod compared to 21 participants affected out of 1000 taking placebo.Based on investigator and participant evaluation, imiquimod treatment and photodynamic therapy resulted in better cosmetic outcomes than cryotherapy and 5-fluorouracil., Authors' Conclusions: For individual lesions, photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy. For field-directed treatments, diclofenac, 5-fluorouracil, imiquimod, and ingenol mebutate had similar efficacy, but their associated adverse events and cosmetic outcomes are different. More direct comparisons between these treatments are needed to determine the best therapeutic approach.

Following the release of the national clinical treatment recommendations for ductal carcinoma in situ (DCIS), consumers' and surgeons' characterisation of this disease was assessed. Telephone interviews were conducted with 231 women diagnosed with DCIS, in Victoria, Australia in 2006/2007 and 63 treating surgeons completed a mailed survey. The main outcome measures were: women's diagnostic experience, women's and surgeons' description of DCIS, women's understanding of DCIS, confusion and worry about the disease and risk perceptions. While the majority of women had not heard of DCIS prior to diagnosis, most reported a positive diagnostic experience. Surgeons' and women's description of DCIS were consistent. Women understood that DCIS is a contained disease (86%), can progress (88%) and treatment aims to prevent invasive cancer (97%). However, only 13% understood that DCIS alone cannot spread to other parts of the body. A quarter of the women were confused about the risk of DCIS spreading. Younger women had more concerns about developing breast cancer (P= 0.008) and the disease spreading (P= 0.002) and rated their risk of invasive disease higher (P= 0.007). Most women diagnosed with DCIS in 2006/2007 understand the 'early, contained nature' of the disease, but understanding of the 'non-invasive' nature of DCIS could be improved., (© 2011 Blackwell Publishing Ltd.)

Background: Cerebral palsy (CP) is "a group of permanent disorders of the development of movement and posture causing activity limitation(s) that are attributed to non-progressive disturbance that occurred in the developing fetal or infant brain" (Rosenbaum 2007, p.9). The spastic motor type is the most common form of CP. Therapeutic management may include splinting/casting, passive stretching, facilitation of posture/movement, spasticity-reducing medication and surgery. Botulinum toxin-A (BoNT-A) is now used as an adjunct to these techniques in an attempt to reduce spasticity, improve range of movement and function., Objectives: To assess the effectiveness of injections of BoNT-A or BoNT-A and occupational therapy in the treatment of the upper limb in children with CP., Search Strategy: We searched the Cochrane Controlled Trials Register/CENTRAL (The Cochrane Library, Issue 3, 2008), MEDLINE (1966 to August Week 1 2008), EMBASE (1980 to 2008 Week 28) and CINAHL (1982 to August Week 1 2008)., Selection Criteria: All randomised controlled trials (RCTs) comparing BoNT-A injection or BoNT-A injection and occupational therapy in the upper limb(s) with other types of treatment (including no treatment or placebo) in children with CP., Data Collection and Analysis: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity and rated for quality using the PEDro scale. Data were extracted and entered into RevMan 5.0.15., Main Results: Ten trials met the inclusion criteria. PEDro quality ratings ranged from 6/10 to 10/10. Concentration of BoNT-A ranged from 50U/1.0ml to 200U/1.0ml saline with doses of 0.5U to 16U/kg body weight and total doses of 220 to 410 Units (Botox(R)).A combination of BoNT-A and occupational therapy is more effective than occupational therapy alone in reducing impairment, improving activity level outcomes and goal achievement, but not for improving quality of life or perceived self-competence. When compared with placebo or no treatment, there is moderate evidence that BoNT-A alone is not effective., Authors' Conclusions: This systematic review found high level evidence supporting the use of BoNT-A as an adjunct to managing the upper limb in children with spastic CP. BoNT-A should not be used in isolation but should be accompanied by planned occupational therapy.Further research is essential to identify children most likely to respond to BoNT-A injections, monitor longitudinal outcomes, determine timing and effect of repeated injections and the most effective dosage, dilution and volume schedules. The most effective adjunct therapies including frequency and intensity of delivery also requires investigation.

Background: A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established., Objectives: To assess the efficacy and safety of all interventions used in the management of pemphigus vulgaris and pemphigus foliaceus., Search Strategy: We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international pemphigus meetings and contacted experts in the field., Selection Criteria: Randomised controlled trials of any intervention in pemphigus vulgaris or pemphigus foliaceus., Data Collection and Analysis: Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies., Main Results: Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase.There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41)., Authors' Conclusions: There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.

Background: Treatments for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty, are not always effective. When they are, long-term benefits may not be maintained and osteoarthritis may develop, resulting in the need for a total knee replacement. An alternative is the surgical implantation of healthy cartilage cells into damaged areas (autologous cartilage implantation)., Objectives: To determine the effectiveness of autologous cartilage implantation (ACI) in people with full thickness articular cartilage defects of the knee., Search Strategy: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (15 December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to December 2005), CINAHL (1982 to December Week 2, 2004), EMBASE (1988 to 2005 Week 50), SPORTDiscus (1830 to January 2005) and the National Research Register Issue 3, 2005., Selection Criteria: Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, femoral trochlea or patella., Data Collection and Analysis: Two review authors selected studies for inclusion independently. We assessed study quality based on adequacy of the randomisation process, adequacy of the allocation concealment process, potential for selection bias after allocation and level of masking. Data was not pooled due to clinical and methodological heterogeneity in the studies., Main Results: We included four randomised controlled trials (266 participants). One trial of ACI versus mosaicplasty reported statistically significant results for ACI at one year, but only in a post-hoc subgroup analysis of participants with medial condylar defects; 88% had excellent or good results with ACI versus 69% with mosaicplasty. A second trial of ACI versus mosaicplasty found no statistically significant difference in clinical outcomes at two years. There was no statistically significant difference in outcomes at two years in a trial comparing ACI with microfracture. In addition, one trial of matrix-guided ACI versus microfracture did not contain enough long-term results to reach definitive conclusions., Authors' Conclusions: The use of ACI and other chondral resurfacing techniques is becoming increasingly widespread. However, there is at present no evidence of significant difference between ACI and other interventions. Additional good quality randomised controlled trials with long-term functional outcomes are required.

Background: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than 1 atmosphere in a pressure vessel. This technology has been used to treat a variety of disease states and has been described as helping patients who have sustained burns., Objectives: The aim of this review was to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of thermal burns., Search Strategy: We searched the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (Ovid 1966 to November Week 2, 2003), CINAHL (Ovid 1982 to December Week 2 2003), EMBASE (Ovid 1980 to September 2003), DORCTHIM (Database of Randomised Controlled Trials in Hyperbaric Medicine) from inception to 2003, and reference lists of articles., Selection Criteria: We included all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham)., Data Collection and Analysis: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data was extracted and entered into RevMan 4.2.3., Main Results: Four randomised controlled trials were identified, of which two satisfied the inclusion criteria. The trials were of poor methodological quality. As a result, it was difficult to have confidence in the individual results and it would not have been appropriate to attempt to pool the data. One trial reported no difference in length of stay, mortality, or number of surgeries between the control and HBO-treated groups once these variables were adjusted for the patient's condition. The second trial reported mean healing times that were shorter in patients exposed to HBOT (mean: 19.7 days versus 43.8 days)., Reviewers' Conclusions: This systematic review has not found sufficient evidence to support or refute the effectiveness of HBOT for the management of thermal burns. Evidence from the two randomised controlled trials is insufficient to provide clear guidelines for practice. Further research is needed to better define the role of HBOT in the treatment of thermal burns.

Background: A variety of strategies have been employed for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty. These treatments are not always effective and when they are, the benefits may only be transitory. Unsuccessfully treated cartilage damage may progress to degenerative disease states and result in the need for a total knee replacement. In recent years the surgical implantation of healthy cartilage cells (autologous cartilage implantation [ACI] ) into damaged areas has been seen as an alternative option and is currently under investigation as a potential improvement over the current strategies for the management and treatment of articular cartilage defects., Objectives: To determine the effectiveness of ACI in patients with full thickness articular cartilage defects of the knee., Search Strategy: We searched the Cochrane Musculoskeletal Injuries Group specialised register (May 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to June Week 4 2001), CINAHL (1982 to July Week 2 2001), EMBASE (1980 to 2001 Week 27), SPORTDiscus (1949 to June 2001), Current Contents (1993 Week 26 to 2001 Week 30) and the National Research Register (Issue 2, May 2002)., Selection Criteria: Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, trochlea or patella., Data Collection and Analysis: Two independent reviewers applied the entry criteria to identified studies., Main Results: No completed randomised controlled trials investigating this treatment were identified through the above searches. One possible trial has been placed in Studies Awaiting Assessment, awaiting translation of the full trial report. Ongoing trials currently underway will be incorporated in future updates of this review., Reviewer's Conclusions: No information is available from RCTs which can influence current practice. Therefore, since current evidence is subject to the inherent weaknesses of case series or reports, ACI must currently be considered as a technology under investigation whose effectiveness is yet to be determined in well designed and conducted clinical trials. The results of ongoing randomised clinical trials will help improve this situation.

The subcellular localization and different biochemical properties of a human hepatic microsomal enzyme that hydrolyses paraoxon (paraoxonase, PON1) were studied and compared to the paraoxon hydrolase activity found in human plasma as well as in rat liver and plasma. Having evaluated the influence of the postmortem interval by a parallel experiment performed in rats, we conclude that the paraoxonase activity was preferentially localized in the microsomal fraction. The enzyme reaction was optimized according to temperature, pH, buffer, ionic strength, substrate concentration, and enzyme protein concentration. The characterization of human liver paraoxonase included the study of optimum pH, pH stability, heat inactivation assays, and kinetic parameters (K(m) and Vmax). In addition, the enzyme activity showed an absolute requirement for exogenous calcium. The activity was lost after incubation with EDTA and partially restored by the addition of calcium; however, other metals assayed were not able to activate the human liver enzyme as did calcium. Our results support the possible identity between human plasma and liver paraoxonases. In spite of the technical difficulties of this study and the possible interference of the postmortem changes in the results, this article represents the first systematic approach to the characterization of human liver paraoxonase.