A proposed methodology for uncertainty extraction and verification in priority setting partnerships with the James Lind Alliance: an example from the Common Conditions Affecting the Hand and Wrist Priority Setting Partnership.

BACKGROUND: To report our recommended methodology for extracting and then confirming research uncertainties - areas where research has failed to answer a research question - derived from previously published literature during a broad scope Priority Setting Partnership (PSP) with the James Lind Alliance (JLA). METHODS: This process was completed in the UK as part of the PSP for "Common Conditions Affecting the Hand and Wrist", comprising of health professionals, patients and carers and reports the data (uncertainty) extraction phase of this. The PSP followed the robust methodology dictated by the JLA and sought to identify knowledge gaps, termed "uncertainties" by the JLA. Published Cochrane Systematic Reviews, Guidelines and Protocols, NICE (National Institute for Health and Care Excellence) Guidelines, and SIGN (Scottish Intercollegiate Guidelines Network) Guidelines were screened for documented "uncertainties". A robust method of screening, internally verifying and then checking uncertainties was adopted. This included independent screening and data extraction by multiple researchers and use of a PRISMA flowchart, alongside steering group consensus processes. Selection of research uncertainties was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP which focused on "common" hand conditions routinely treated by hand specialists, including hand surgeons and hand therapists limited to identifying questions concerning the results of intervention, and not the basic science or epidemiology behind disease. RESULTS: Of the 2358 records identified (after removal of duplicates) which entered the screening process, 186 records were presented to the PSP steering group for eligibility assessment; 79 were deemed within scope and included for the purpose of research uncertainty extraction (45 full Cochrane Reviews, 18 Cochrane Review protocols, 16 Guidelines). These yielded 89 research uncertainties, which were compared to the stakeholder survey, and added to the longlist where necessary; before derived uncertainties were checked against non-Cochrane published systematic reviews. CONCLUSIONS: In carrying out this work, beyond reporting on output of the Common Conditions Affecting the Hand and Wrist PSP, we detail the methodology and processes we hope can inform and facilitate the work of future PSPs and other evidence reviews, especially those with a broader scope beyond a single disease or condition.

The global incidence of bullous pemphigoid: a systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. OBJECTIVES: The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. METHODS: Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. RESULTS: Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8-13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2-60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8-18·2) and 5·6 (95% CI 3·5-9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0-29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. CONCLUSIONS: The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.

What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 2: treatment.

This review forms part of a series of annual evidence updates on atopic eczema (AE), and provides a summary of key findings from systematic reviews (SRs) published or indexed in 2019 related to AE treatment. Several SRs assessed the efficacy of topical corticosteroids (TCS), topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors and topical Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors. However, there is a lack of good-quality trials comparing topical treatment agents with TCS, which remain the standard of care for patients with AE. Most of the included trials lack meaningful comparisons as they used vehicle as a comparator. There is also lack of harmonization of outcome measures for AE across studies. Large, well-designed RCTs are needed to further determine whether any specific emollients offer superior benefit. There is evidence highlighting limited benefit of oral H1 antihistamines as 'add-on' therapy to topical treatment of eczema. Mycophenolate mofetil may have a role in patients with refractory AE. Among biologic therapies, most of the efficacy data relate to dupilumab. Furthermore, there is growing evidence for the efficacy and safety of systemic JAK/STAT pathway inhibitors, but the existing data are of low quality.

What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 1: Risk factors and prevention.

This review is part of an annual evidence update on atopic eczema (AE), providing a summary of key findings from 18 systematic reviews published in 2019 on AE risk factors and prevention. Parental atopy, particularly AE, is a risk factor for offspring AE, and this risk is augmented both by the number of parental atopic diseases present and the number of affected parents. Low-quality evidence suggests that autumn or winter birth increases childhood AE risk compared with birth in spring. There is some evidence to support filaggrin gene-environment interactions; however, this is limited by small underpowered studies. There is no evidence to suggest that polymorphisms in the -1082, -592 and -819 loci of the interleukin-10 gene increase susceptibility to AE. There is no robust evidence to support a relationship between childhood AE development and either yoghurt consumption in the first year of life, gut microbiota variants, prenatal or infantile paracetamol exposure, maternal antibiotic exposure or air pollution. Three systematic reviews investigated the effect of probiotics given during pregnancy or infancy; although low-quality evidence suggests benefits of combined probiotics, these studies were limited by significant heterogeneity. No relationship between the age at which complementary food and beverages are introduced and the risk of developing AE in infancy was identified. Consistent evidence showed no relationship between human milk feeding and infant AE development, aside from limited evidence suggesting a protective role in those with atopic heredity. This summary of recent evidence related to AE risk factors and prevention highlights the complex aetiology of AE.

Global Guidelines in Dermatology Mapping Project (GUIDEMAP): a scoping review of dermatology clinical practice guidelines.

BACKGROUND: Clinical practice guidelines (CPGs) play a critical role in standardizing and improving treatment outcomes based on the available evidence. It is unclear how many CPGs are available globally to assist clinicians in the management of patients with skin disease. OBJECTIVES: To search for and identify CPGs for dermatological conditions with the highest burden globally. METHODS: We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A systematic literature search was done to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. RESULTS: A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had a relatively high CPG representation but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource-poor settings being under-represented. The skin disease categories of the CPGs correlated weakly with the GBD disability-adjusted life-years metrics. Eighty-nine CPGs did not have funding disclosures and 34 CPGs were behind a paywall. CONCLUSIONS: The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and reporting of funding. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarizing these findings.

Measurement properties of patient-reported outcome measures for eczema control: a systematic review.

Atopic eczema (herein referred to as 'eczema') is a skin disease characterized by remitting and relapsing symptoms. The Harmonising Outcome Measures for Eczema (HOME) initiative was developed to establish a core outcome set (COS) for eczema to be measured for all future eczema trials. The core outcome set for atopic eczema clinical trials includes the domain for patient-reported eczema control, but a review of the validation of available eczema control instruments was lacking. We aimed to review the literature and systematically assess the measurement properties of validated patient-reported outcome instruments that capture eczema control. PubMed and Ovid EMBASE were searched up to 24 January 2020 for any study that reported on PROM instrument development or validation. The COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria were used to assess the quality of eligible studies. We screened 12 036 titles and abstracts and 58 full texts. A total of 12 papers were included, reporting on seven PROMS. These were assessed with respect to development, reliability, construct validity and responsiveness. Two instruments, Recap of Atopic Eczema (RECAP) and the Atopic Dermatitis Control Tool (ADCT), have been developed and validated to a sufficient standard to support their recommendation as patient-reported outcome instruments for measuring control of atopic eczema as part of the HOME Core Outcome Set.

Laser therapy for genital lichen sclerosus: A systematic review of the current evidence base.

Background: Lichen sclerosus (LS) is a chronic, inflammatory dermatosis. Initial treatment with superpotent topical corticosteroids is the accepted and evidence-based first-line therapy. For those who do not respond after exclusion of other potentiating factors, the best second-line therapy is unclear. Laser therapy is an emerging treatment for genital LS and despite uncertain efficacy its use is gaining popularity in the private sector. Objectives: We aimed to review the effectiveness of laser therapy for genital LS in men, women and children. Methods: We conducted a systematic review of all primary studies reporting the use of laser in genital LS. Ovid MEDLINE, PubMed, Ovid Embase, Cochrane CENTRAL, Web of Science, CINAHL and PsycINFO were searched from inception to February 2021. The quality of the studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials, ROBINS-I tool for non-randomized trials and Joanna Briggs Institute checklist for case studies. Results: A total of 24 studies, involving 616 adults, met inclusion criteria. These were six randomized controlled trials (RCTs), one non-randomized trial, nine single arm trials and eight case series. Where assessed, most studies suggest that laser therapy in patients with LS may improve symptoms, clinical signs, quality of life and sexual function. However, results were highly heterogeneous and methodological quality was very low, therefore meta-analysis was not possible. Conclusions: There is poor evidence to support the use of laser therapy for genital LS at present. Effectiveness of laser needs to be robustly investigated in well-conducted RCTs.

Can atopic eczema and psoriasis coexist? A systematic review and meta-analysis.

Importance: Previous studies report both coexistence and mutual exclusivity of atopic eczema (AE) and psoriasis, but these have not been appraised systematically. Knowledge of such disease association throws light on disease mechanisms and may influence therapeutic choices. Objective: To summarise evidence for AE and psoriasis occurring in the same person at the same point in time. Planned primary outcome was the incidence, prevalence or risk of psoriasis or eczema. Methods: Ovid MEDLINE and Ovid Embase were searched from inception to 1st February 2020. The search strategy was built around the key terms 'atopic eczema', 'psoriasis' and 'co-existence'. Observational studies (cohort, case-control, cross-sectional and case-series) with a minimum of 10 consecutive patients were included. There were no restrictions on participants, geography or language. Studies were selected, data extracted and critically appraised by two independent reviewers. Data were extracted on the method of diagnosis: health professional (dermatologist, criteria, other), self-reported, not specified. Study quality was assessed using validated Joanna Brigg's Institute critical appraisal tools. A random-effects model was used to combine studies. The effect of study quality on the pooled estimate was investigated using stratification. Heterogeneity was explored by subgroup analysis. Results: This review included 31 studies and 20 523 individuals with psoriasis and 1 405 911 with AE. Eight studies reported the prevalence of AE in those with psoriasis and values ranged from 0.17% to 20%: the pooled prevalence was 2% (95% confidence interval [CI]: 1, 3). Seven studies reported the prevalence of psoriasis in those with AE and values ranged from 0.3% to 12.6%; the pooled prevalence was 2% (95% CI: 1, 3). Ten studies were assessed as low risk of bias. Geographical area, method of diagnosis, setting and whether the assessment of diagnosis was blinded, partly contributed to the heterogeneity. Conclusions: This review provides some evidence for the coexistence of AE and psoriasis. Clinicians should be aware of coexistence at diagnosis, when selecting therapies and when reviewing poor response to treatment.

Clinical response to antibiotic regimens in lower limb cellulitis: a systematic review.

There is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen. Many patients with cellulitis fail to respond to first-line antibiotics. This can negatively affect patient care and result in unnecessary hospital admissions. The aim of this systematic review was to determine the clinical response and safety of antibiotic regimens for the management of LLC. A systematic review for randomized controlled trials (RCTs) was conducted using OVID MEDLINE, Ovid Embase and Cochrane Central Register of Controlled Trials in January 2019. Outcomes of interest included the clinical response to antibiotic regimens (type, dose, route, duration) and the safety of antibiotics in LLC. Trial quality was identified using the Cochrane Risk of Bias tool. Four RCTs were included. All included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration or dose. LLC may be overtreated and shorter courses of oral antibiotics, possibly with lower doses, may be more suitable. There is a lack of published data on the clinical response and safety of antibiotics in LLC. Three studies were high risk for bias overall. Further high-quality studies may help determine whether less intensive antibiotic regimens can effectively treat LLC.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 1: prevention and topical therapies.

This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long-chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow's milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic-pituitary-adrenal axis suppression following 2-4 weeks of treatment with low-potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 2: systemic therapies.

This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2017. Part 2: epidemiology, aetiology and risk factors.

This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin-31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention-deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction.

What's new in atopic eczema? An analysis of systematic reviews published in 2017. Part 1: treatment and prevention.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It provides a summary of key findings from 25 systematic reviews that were published or indexed during 2017, and focuses on the treatment and prevention of AE. There is high-quality evidence to demonstrate that dupilumab is better than placebo for the treatment of AE, is not associated with a higher incidence of adverse effects and does not increase the risk of infection compared with placebo; however, comparison studies with other systemic treatments are necessary. Topical tofacitinib is a promising treatment for mild-moderate AE, but currently lacks sufficient evidence from well-designed randomized controlled trials (RCTs) comparing with other active treatments. Topical doxepin may be effective for pruritus in AE, but available studies have short follow-up periods and longer-term outcomes are needed. Bleach baths were no more effective than water baths alone at reducing AE severity. Topical antibiotics cannot be recommended for infected AE, owing to insufficient evidence of benefit. There is little comparison of different emollients in RCTs, but overall evidence indicates that they reduce AE severity, are steroid-sparing and lead to better outcomes in combination with topical corticosteroids (TCS) than TCS alone. No clear benefit was demonstrated for vitamin D/C/E supplementation in pregnancy for eczema prevention.

A systematic review showing the lack of diagnostic criteria and tools developed for lower-limb cellulitis.

BACKGROUND: Cellulitis can be a difficult diagnosis to make. Furthermore, 31% of patients admitted from the emergency department with suspected lower-limb cellulitis have been misdiagnosed, with incorrect treatment potentially resulting in avoidable hospital admission and the prescription of unnecessary antibiotics. OBJECTIVES: We sought to identify diagnostic criteria or tools that have been developed for lower-limb cellulitis. METHODS: We conducted a systematic review using Ovid MEDLINE and Embase databases in May 2018, with the aim of describing diagnostic criteria and tools developed for lower-limb cellulitis, and we assessed the quality of the studies identified using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We included all types of study that described diagnostic criteria or tools. RESULTS: Eight observational studies were included. Five studies examined biochemical markers, two studies assessed imaging and one study developed a diagnostic decision model. All eight studies were considered to have a high risk for bias in at least one domain. The quantity and quality of available data was low and results could not be pooled owing to the heterogeneity of the findings. CONCLUSIONS: There is a lack of high-quality publications describing criteria or tools for diagnosing lower-limb cellulitis. Future studies using prospective designs, validated in both primary and secondary care settings, are needed. What's already known about this topic? Diagnosing lower-limb cellulitis on first presentation is challenging. Approximately one in three patients admitted from the emergency department with suspected lower-limb cellulitis do not have cellulitis and are given another diagnosis on discharge. Consequently, this results in potentially avoidable hospital admissions and the prescription of unnecessary antibiotics. There are no diagnostic criteria available for lower-limb cellulitis in the U.K. What does this study add? This systematic review has identified a key research gap in the diagnosis of lower-limb cellulitis. There is a current lack of robustly developed and validated diagnostic criteria or tools for use in clinical practice.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 2: Epidemiology, aetiology and risk factors.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE), providing a succinct guide for clinicians and patients. It presents the key findings from 14 systematic reviews published in 2016, focusing on AE epidemiology, aetiology and risk factors. For systematic reviews on the treatment and prevention of AE and for nomenclature and outcome assessments, see Parts 1 and 3 of this update, respectively. The annual self-reported prevalence of AE is a range of 11.4-24.2%, compared with a general practioner-diagnosed prevalence of 1.8-9.5%. The mean age of AE diagnosis is 1.6 years. Persistent AE is associated with more severe disease at the time of diagnosis, onset after the age of 2 years and female sex. There is a significant association between having AE and subsequent development of food allergy. Food allergy is also associated with more severe and persistent AE. No consistent association was found between the timing of allergenic food introduction and the risk of developing AE. Evidence from heterogeneous studies indicates that skin absorption is increased in patients with AE, and that there is increased colonization with Staphylococcus aureus in lesional and nonlesional skin and the nasal mucosa of patients with AE compared with controls. There is uncertain evidence indicating an association between AE and smoking exposure, antenatal infection and low maternal vitamin D levels during pregnancy. Weak evidence suggests an increased risk of basal cell carcinoma, but not of melanoma or squamous cell carcinoma, while the risk of glioma is reduced.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 3: nomenclature and outcome assessment.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It presents the key findings from 11 systematic reviews published in 2016 that focus on AE outcome assessment, disease impact and nomenclature. Systematic reviews on the treatment and prevention of AE are summarized in Part 1 of this update, and systematic reviews on the epidemiology of and risk factors for AE are summarized in Part 2. Six reviews summarized what outcome measurement instruments have been used in published AE trials, or summarized validation studies for the available instruments. These reviews were used to inform consensus decisions by the Harmonising Outcome Measures for Eczema initiative. Although validated instruments exist for clinical signs and patient-reported symptoms, there are currently no validated instruments for capturing quality of life or long-term control. Four reviews examined the impact of AE on children and their families, but few studies were included. One birth cohort study found no association between AE and educational attainment at 11 years. AE has a moderate impact on health-related quality of life and a substantial impact on family life. AE is a major risk factor for occupational hand dermatitis, and it is advised that young atopic individuals are informed about high-risk occupations. Further efforts are required to standardize the nomenclature for AE, which is also commonly known as 'atopic dermatitis' or 'eczema', and preferred terms vary around the world.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid-containing preparation (Atopiclair® ), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once-daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE.

A systematic review of local antibiotic devices used to improve wound healing following the surgical management of foot infections in diabetics.

AIMS: Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery. MATERIALS AND METHODS: Databases were searched to identify eligible studies and 13 were identified for inclusion. RESULTS: Overall, the quality of the studies was poor. A single trial suggested that wound healing is quicker when a gentamicin-impregnated collagen sponge was implanted at time of surgery, with no difference in length of stay or rate of amputation. Results from studies with high risk of bias indicated no change in wound healing when a gentamicin-impregnated sponge was implanted during transmetatarsal amputation, but a reduction in the incidence of wound breakdown (8% vs 25%, not statistically significant) was identified. A significant cost reduction was identified when using an antimicrobial gel to deliver antibiotics and anti-biofilm agents (quorum-sensing inhibitors) compared with routine dressings and systemic antibiotics. Analyses of case series identified 485 patients who were treated using local antibiotic delivery devices. The rates of wound healing, re-operation, and mortality were comparable to those that have been previously reported for the routine management of these infections. CONCLUSION: There is a lack of good-quality evidence to support the use of local antibiotic delivery devices in the treatment of foot infections in patients with diabetes. Cite this article: Bone Joint J 2018;100-B:1409-15.

Alpha-defensin and the Synovasure lateral flow device for the diagnosis of prosthetic joint infection: a systematic review and meta-analysis.

Aims: The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI). Materials and Methods: Studies using alpha-defensin or Synovasure (Zimmer Biomet, Warsaw, Indiana) to diagnose PJI were identified from systematic searches of electronic databases. The quality of the studies was evaluated using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) tool. Meta-analysis was completed using a bivariate model. Results: A total of 11 eligible studies were included. The median QUADAS score was 13 (interquartile range 13 to 13) out of 14. Significant conflicts of interest were identified in five studies. The pooled sensitivity for the laboratory alpha-defensin test was 0.95 (95% confidence interval (CI) 0.91 to 0.98) and the pooled specificity was 0.97 (95% CI 0.95 to 0.98) for four studies with a threshold level of 5.2 mgl-1 The pooled sensitivity for the lateral flow cassette test was 0.85 (95% CI 0.74 to 0.92) and the pooled specificity was 0.90 (95% CI 0.91 to 0.98). There was a statistically significant difference in sensitivity (p = 0.019), but not specificity (p = 0.47). Conclusion: Laboratory-based alpha-defensin testing remains a promising tool for diagnosing PJI. The lateral flow cassette has a significantly lower performance and pooled results are comparable to the leucocyte esterase test. Further studies are required before the widespread adoption of the lateral flow cassette alpha-defensin test. Cite this article: Bone Joint J 2018;100-B:703-11.