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.

Dermatological games: Part 2. What has changed 40 years on?

In this two-part report, we review and critically appraise 'Dermatological games' by J. A. Cotterill, a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. Part 1 described and critically appraised the educational value of Cotterill's original list of games in relation to how they apply to dermatology practice. In Part 2, a list of new 'games' that might be observed in current dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his article remains relevant to dermatology practice and training today is scrutinized, in order to stimulate discussion and improve patient care.

Dermatological games: Part 1. Original description and critique.

'Dermatological games' by J. A. Cotterill was a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. In Part 1 of this series of two reviews, we review Cotterill's original list of games and how they applied to dermatology in the context of when they were written. We then critically appraise Cotterill's article and arguments. Although the article was deliberately provocative, we found Cotterill's arguments to be well-structured and logical, and the 'games' described are well-conceived. Cotterill's candid analysis of doctors' motivations and the potential impact on the patient is refreshing and insightful. It is striking that, 40 years on, many of the original 'games' described remain recognizable in current practice. In Part 2, a list of new 'games' that might be observed in modern dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his educational article remains relevant to dermatology practice and training today is scrutinized in order to stimulate discussion, promote education and improve patient care.

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.

'Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta-analysis of randomized controlled trial': a critical appraisal.

AIM: Jia and He aimed 'to compare the efficacy and safety of imiquimod with other treatments in patients with basal cell carcinoma' (BCC). DESIGN AND INCLUSION CRITERIA: Meta-analysis of studies that included patients with histologically confirmed BCC treated with imiquimod 5% cream compared with all other treatments, including vehicle, excisional surgery, cryosurgery, fluorouracil and methyl aminolaevulinate photodynamic therapy. OUTCOMES: The main outcome measures included histological and composite clearance rates, success rates, complete response rates, tumour-free survival and adverse events. RESULTS: Thirteen studies with a total of 4265 patients were included in the review. Pooled analyses comparing imiquimod with all or any of the listed comparators, including vehicle, demonstrated higher histological clearance rates [risk ratio (RR) 9·28, 95% confidence interval (CI) 5·56-15·5; P < 0·001], higher composite clearance rates (RR 34·2, 95% CI 21·3, 55·1; P = 0·001), no significant difference in success rates (RR 0·98, 95% CI 0·89-1·08; P = 0·73), higher complete response rates (RR 3·15, 95% CI 1·55-6·38; P = 0·001), no significant difference in tumour-free survival (RR 1·15, 95% CI 0·98-1·35; P = 0·088) and increased incidence of adverse events (RR 2·00, 95% CI 1·39-2·88; P < 0·001). CONCLUSIONS: The authors state that 'imiquimod significantly exhibited benefit effect in improving the histological/composite clearance rates' compared with other treatments, and they suggest it could be used as the first-choice treatment for patients with BCC. COMMENT: The main concerns related to the article by Jia and He are that the research question is replicative, it makes little sense to combine all BCC types in a meta-analysis, and it also makes no sense to combine an active treatment against a combination of vehicle and other active treatments. There are also concerns about bias related to the use of the same study data more than once in a meta-analysis. Furthermore, we have identified an example of covert duplicate publication, which further compounds the profusion of misleading systematic reviews.

Skin disease profile of Syrian refugees in Jordan: a field-mission assessment.

BACKGROUND: Since the beginning of the Syrian war in 2011, the world has faced the most severe refugee crisis in history and 5.6 million Syrians have sought asylum in neighbouring countries or in Europe. According to recent estimates, more than 650 000 Syrian refugees are displaced in Jordan. OBJECTIVES: This article aims to assess the demographic characteristics and skin disease profile of Syrian displaced people residing in Al Za'atari camp and in communities in Jordan. Furthermore, the authors discuss the barriers to healthcare provision experienced during field missions. METHODS: This is a retrospective analysis of medical records collected during three medical missions in Jordan by an international dermatological team. Data on patient age, gender, country of origin and skin disease diagnoses were recorded both in Al Za'atari camp and Jordanian towns near the Syrian border. RESULTS: A total of 1197 patients were assessed during the field missions, with 67.7% female and 37.1% under the age of 14 years. Dermatitis was the leading dermatological condition in both refugee camp and community healthcare clinics. Infectious diseases were the second most common; however, fungal presentations were more common in the community as opposed to viral in Al Za'atari. CONCLUSIONS: High dermatitis presentations were likely secondary to the environment, living conditions and lack of access to emollients. Infectious diseases were postulated secondary to poor hygiene and sharing of overcrowded spaces. Barriers to health care included limited pharmacological formulary, difficulty in continuity of care and case referrals due to lack of specialized services. Better access to health care, improvement of living conditions and hygiene, and increased availability of medications including emollients and sunscreens are all interventions that should be carried out to reduce skin disease burden. Our findings should further urge the international community to uphold their commitments and uptake engagement in improving health care for Syrian displaced people.

NICE guidance and current practise of recurrent and bilateral groin hernia repair by Scottish surgeons.

BACKGROUND: NICE (National Institute of Health and Clinical Excellence) in England recommended laparoscopic repair for recurrent and bilateral groin hernias in 2004. The aims of this survey were to evaluate the current practise of bilateral and recurrent inguinal hernia surgery in Scotland and surgeons' views on the perceived need for training in laparoscopic inguinal hernia repair (LIHR). METHODS: A postal questionnaire was sent to Scottish consultant surgeons included in the Scottish Audit of Surgical Audit database 2007, asking about their current practice of primary, recurrent and bilateral inguinal hernia surgery. A response was considered valid if the surgeon performed groin hernia surgery; further analysis was based on this group. Those who did not offer LIHR were asked to comment on the possible reasons, and also the perceived need for training in laparoscopic hernia surgery. Only valid responses were stored on Microsoft Excel (Microsoft Corporation, USA) and analysed with SPSS software version 13.0 (SPSS, Chicago, Illinois). RESULTS: Postal questionnaires were sent to 301 surgeons and the overall all response rate was 174/301 (57.8%). A valid response was received from 124 of 174 (71.2%) surgeons and analysed further. Open Lichtenstein's repair seems to be the most common inguinal hernia repair. Laparoscopic surgery was not performed for 26.6 and 31.5% of recurrent and bilateral inguinal hernia, respectively. About 15% of surgeons replied that an LIHR service was not available in their base hospital. Lack of training, financial constraints, and insufficient evidence were thought to be the main reasons for low uptake of LIHR. About 80% of respondents wished to attend hands-on training in hernia surgery. CONCLUSIONS: Current practice by Scottish surgeons showed that one in three surgeons did not offer LIHR for bilateral and recurrent inguinal hernia as recommended by NICE. There is a clear need for training in LIHR.

Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.

BACKGROUND: A transcription regulatory complex (TRC) that includes Ets1, Ets2, PEA3 and ß-catenin/T-cell factors regulates osteopontin (OPN) that is implicated in colorectal cancer (CRC) dissemination. The consistency of OPN transcriptional control between primary CRC and metastases is unclear. This study investigates expression and prognostic significance of the OPN-TRC in primary human CRC and associated colorectal liver metastases (CRLM). METHODS: Osteopontin-TRC factors were assayed by digital microscopy in 38 primary CRCs and matched CRLM specimens and assessed against clinical prognosis. RESULTS: In primary CRC, OPN expression intensity correlated with that of its co-activators, PEA3 (r=0.600; P<0.01), Ets1 (r=0.552; P<0.01), Ets2 (r=0.521; P<0.01) and had prognostic significance. Osteopontin intensity in primary CRC inversely correlated with the interval between diagnosis and resection of CRLM. Overall OPN intensity was lower in CRLM than primary CRC and correlations with co-activators were weaker, for example, Ets1 (P=0.047), PEA3 (P=0.022) or nonsignificant (Ets2). The ratio of OPN expression in CRLM vs primary CRC had prognostic significance. CONCLUSION: This study supports transcriptional control of OPN by known coregulators in both primary and secondary CRC. Weaker associations in CRLM suggest involvement of other unknown factors possibly from the liver microenvironment or resulting from additional genetic or epigenetic changes that drive tumour metastatic capability in OPN transcriptional control.

Open reduction and endobutton fixation of displaced fractures of the lateral end of the clavicle in younger patients.

Displaced fractures of the lateral end of the clavicle in young patients have a high incidence of nonunion and a poor functional outcome after conservative management. Operative treatment is therefore usually recommended. However, current techniques may be associated with complications which require removal of the fixation device. We have evaluated the functional and radiological outcomes using a novel technique of open reduction and internal fixation. A series of 16 patients under 60 years of age with displaced fractures of the lateral end were treated by open reduction and fixation using a twin coracoclavicular endobutton technique. They were followed up for the first year after their injury. At one year the mean Constant score was 87.1 and the median Disabilities of the Arm, Shoulder and Hand score was 3.3. All fractures had united, except in one patient who developed an asymptomatic fibrous union. One patient had post-traumatic stiffness of the shoulder, which resolved with physiotherapy. None required re-operation. This technique produces good functional and radiological outcomes with a low prevalence of complications and routine implant removal is not necessary.

Proximal humeral fractures with a severe varus deformity treated by fixation with a locking plate.

We treated 47 patients with a mean age of 57 years (22 to 88) who had a proximal humeral fracture in which there was a severe varus deformity, using a standard operative protocol of anatomical reduction, fixation with a locking plate and supplementation by structural allografts in unstable fractures. The functional and radiological outcomes were reviewed. At two years after operation the median Constant score was 86 points and the median Disabilities of the Arm, Shoulder and Hand score 17 points. Seven of the patients underwent further surgery, two for failure of fixation, three for dysfunction of the rotator cuff, and two for shoulder stiffness. The two cases of failure of fixation were attributable to violation of the operative protocol. In the 46 patients who retained their humeral head, all the fractures healed within the first year, with no sign of collapse or narrowing of the joint space. Longer follow-up will be required to confirm whether these initially satisfactory results are maintained.