Fiona Bath-Hextall

A systematic review of worldwide incidence of nonmelanoma skin cancer

Backgroundu2002 Nonmelanoma skin cancer (NMSC) is the most common cancer affecting white‐skinned individuals and the incidence is increasing worldwide.

Trends in incidence of skin basal cell carcinoma. Additional evidence from a UK primary care database study.

We determined the trends in incidence of skin basal cell carcinoma (BCC) using a primary care population‐based cohort study in the UK. 11,113 adults with a BCC diagnosis were identified from a total of 7.22 million person‐years of data between 1996 and 2003 from the Health Improvement Network database. From a random subsample of BCC cases identified from the database, 93% were confirmed by hospital letter and/or pathology report. The incidence of BCC was 153.9 per 100,000 person‐years (95% CI 151.1, 156.8) and was slightly higher in men as compared to women (Incidence Rate Ratio 1.10, 95% CI 1.06, 1.14). There was a 3% increase year on year across the study period (IRR 1.03, 95% CI 1.01, 1.04), with the largest increase in incidence seen in the 30–39 year age groups, although this did not reach statistical significance. Our study indicates 53,000 new cases of BCC are estimated every year in the UK and figures are continuing to rise on a yearly basis. Incidence rates are highest for men and in particular in the older age categories. These findings are consistent with those reported for various other populations. We have also found an increase in incidence in ages 30–39, which may suggest a cohort effect of increasing ultraviolet exposure in successive younger generations. This may have a huge public and service impact in future years in countries such as the UK, with predominantly fair‐skinned population, with high leisure exposure to ultraviolet light. Our findings underline the need for more elaborate preventive measures.

Interventions for dysphagia in acute stroke

BACKGROUNDnIt is unclear how dysphagic patients should be fed and treated after acute stroke.nnnOBJECTIVESnThe objective of this review was to assess the effect of different management strategies for dysphagic stroke patients, in particular how and when to feed, whether to supplement nutritional intake, and how and whether to treat dysphagia.nnnSEARCH STRATEGYnWe searched the Cochrane Stroke Group trials register, Medline, Embase, ISI, and existing review articles. We contacted researchers in the field and equipment manufacturers. Date of the most recent searches: March 1999.nnnSELECTION CRITERIAnUnconfounded truly or quasi randomised controlled trials in dysphagic patients with acute/subacute (within 3 months) stroke.nnnDATA COLLECTION AND ANALYSISnThree reviewers independently applied the trial inclusion criteria. Two reviewers assessed trial quality and extracted the data.nnnMAIN RESULTSnPercutaneous endoscopic gastrostomy (PEG) versus nasogastric tube (NGT) feeding: two trials (49 patients) suggest that PEG reduces end-of-trial case fatality (Peto Odds Ratio, OR 0.28, 95% CI 0.09 to 0.89) and treatment failures (OR 0.10, 95% CI 0.02 to 0.52), and improves nutritional status, assessed as weight (Weighted Men Difference, WMD +4.1 kg, 95% CI -4.3 to +12.5), mid-arm circumference (WMD +2.2 cm, 95% CI -0.5 to +4.9) or serum albumin (WMD + 7.0 g/l, 95% CI +4.9 to +9.1) as compared with NGT feeding; two larger studies are ongoing. Timing of feeding: no completed trials; one large study is ongoing. Swallowing therapy for dysphagia: two trials (85 patients) suggest that formal swallowing therapy does not significantly reduce end-of-trial dysphagia rates (OR 0.55, 95% CI 0.18 to 1.66). Drug therapy for dysphagia: one trial (17 patients); nifedipine did not alter end-of-trial case fatality or the frequency of dysphagia. Nutritional supplementation: one trial (42 patients) found a non-significant trend to a lower case fatality, and significantly increased energy and protein intake; one large trial is ongoing and data is awaited from two other studies. Fluid supplementation: one trial (20 patients) found that supplementation did not alter the time to resolution of dysphagia.nnnREVIEWERS CONCLUSIONSnToo few studies have been performed, and these have involved too few patients. PEG feeding may improve outcome and nutrition as compared with NGT feeding. Further research is required to assess how and when patients are fed, and the effect of swallowing or drug therapy on dysphagia.

Probiotics for treating eczema

BACKGROUNDnProbiotics have been proposed as an effective treatment for eczema, and recently a number of clinical trials have been undertaken.nnnOBJECTIVESnTo assess the effects of probiotics for the treatment of eczemannnSEARCH STRATEGYnWe searched the Cochrane Skin Group Specialised Register (to April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2,2008) MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), PsycINFO, AMED and LILACS (from inception to April 2008) and ISI Web of Science (to December 2006) and reference lists of articles. We also searched registries of ongoing clinical trials, conference proceedings and searched for adverse events.nnnSELECTION CRITERIAnRandomised controlled trials of live orally ingested microorganisms for the treatment of eczema.nnnDATA COLLECTION AND ANALYSISnTwo authors independently applied eligibility criteria, assessed the quality of trials and extracted data. We contacted study authors for more information where necessary. We recorded adverse events from the included studies, and from the separate adverse events search.nnnMAIN RESULTSnTwelve randomised controlled trials involving 781 participants met the inclusion criteria. All trial participants were children. There was no significant difference in participant or parent-rated symptom scores in favour of probiotic treatment (5 trials, 313 participants). Symptom severity on a scale from 0 to 20 was 0.90 points lower after probiotic treatment than after placebo (95%CI -1.04, 2.84; p = 0.36).There was also no significant difference in participant or parent-rated overall eczema severity in favour of probiotic treatment (3 trials, 150 participants). There was no significant difference in investigator rated eczema severity between probiotic and placebo treatments (7 trials, 588 participants). On a scale from 0 to 102 investigator rated eczema severity was 2.46 points lower after probiotic treatment than after placebo treatment (95%CI -2.53, 7.45 p = 0.33). Significant heterogeneity was noted between the results of individual studies, which may be explained by the use of different probiotic strains. Subgroup analysis by age of participant, severity of eczema, presence of atopy or presence of food allergy did not identify a population with different treatment outcomes to the population as a whole. The adverse events search identified some case reports of infections and bowel ischaemia caused by probiotics.nnnAUTHORS CONCLUSIONSnThe evidence suggests that probiotics are not an effective treatment for eczema, and probiotic treatment carries a small risk of adverse events.

Interventions for basal cell carcinoma of the skin: systematic review

Abstract Objectives To assess the effects of treatments for basal cell carcinoma. Methods Systematic review of randomised controlled trials. Main outcome measure Recurrence of basal cell carcinoma at three years or beyond, assessed clinically. Studies reviewed Randomised controlled trials of interventions for histologically confirmed basal cell carcinoma (published and unpublished material; no language restrictions). Results 25 studies were identified, covering seven therapeutic categories. Only one study of surgical excision versus radiotherapy contained primary outcome data, which showed significantly more persistent tumours and recurrences in the radiotherapy group compared with surgery (odds ratio 0.09, 95% confidence interval 0.01 to 0.67). One study compared cryotherapy with surgery, with inconclusive results at one year. In a comparison of radiotherapy with cryotherapy, significantly more recurrences occurred at one year in the cryotherapy group. Preliminary studies suggest a short term success rate of 87-88% for imiquimod cream in the treatment of superficial basal cell carcinoma, although this cream has not been compared with surgery. No consistent evidence was found for the other treatment modalities. Conclusions Little good quality research has been done on the treatments used for the most common cancer in humans. Most trials have included only people with basal cell carcinoma occurring at low risk sites. Only one trial measured recurrence at four years; recurrence rates at one year should be interpreted with caution. Surgery and radiotherapy seem to be the most effective treatments; surgery showed the lowest failure rates. Other treatments might have some use but need to be compared with surgery.

Interventions to reduce Staphylococcus aureus in the management of atopic eczema

BACKGROUNDnStaphylococcus aureus can cause secondary infection in atopic eczema, and it may promote inflammation in eczema that does not look infected. Many antimicrobial products exist for eczema, but it is unclear if they work or if they promote bacterial resistance.nnnOBJECTIVESnTo assess the effects of interventions to reduce Staphylococcus aureus for treating infected or uninfected atopic eczema.nnnSEARCH STRATEGYnWe searched the Cochrane Skin Group Specialised Register (March 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2008), MEDLINE (OVID) (from 2002 to March 2008), EMBASE (OVID) (from 2002 to March 2008), Ongoing trials registers (March 2008). References from trials and reviews were searched, pharmaceutical companies were contacted for unpublished trials. There were no language restrictions.nnnSELECTION CRITERIAnRandomised controlled trials (RCTs) of people with atopic eczema who have been treated with a product intended to reduce S. aureus on the skin.nnnDATA COLLECTION AND ANALYSISnTwo people independently performed the study selection, data abstraction and quality assessment.nnnMAIN RESULTSnWe included 21 studies (1018 participants) covering 7 treatment categories. Most studies were poorly reported and study differences limited pooling of results. Adverse effects were especially poorly reported, and only one study reported the emergence of resistant bacterial strains following oral antibiotics. Oral antibiotics were not associated with benefit in non-infected (2 trials, 66 participants) or infected eczema (1 trial, 33 participants). We did not find any benefit for antibacterial soaps (1 trial, 50 participants), or antibacterial bath additives (2 trials, 41 participants), or topical antibiotics/antiseptics (4 studies, 95 participants). Adding antibiotics to topical corticosteroids reduced numbers of Staphylococcus aureus in 4 trials (302 participants), but there was no evidence of any clinical benefit in 9 trials involving 677 participants: betamethasone plus neomycin vs clobetasol (MD 1.2; 95% CI 0.25, 2.15), prednicarbate plus antimicrobial vs prednicarbate (RR 0.64; 95% CI 0.25, 1.68), or betamethasone valerate plus gentamicin vs betamethasone (RR 0.31; 95% CI 0.07, 1.35). One trial (30 participants) showed no significant improvement in eczema for those using silver textiles (RR 2.67; 95% CI 0.98, 7.22), despite using 10 times the amount of topical steroids.nnnAUTHORS CONCLUSIONSnWe failed to find clear evidence of benefit for antimicrobial interventions for people with atopic eczema, despite their widespread use. This does not necessarily mean they do not work because the studies were small and poorly reported. Further large studies with long-term outcomes and clearly defined participants are urgently required.

Dietary exclusions for established atopic eczema

BACKGROUNDnAtopic eczema (AE) is a non-infective chronic inflammatory skin disease characterised by an itchy red rash.nnnOBJECTIVESnTo assess the effects of dietary exclusions for the treatment of established atopic eczema.nnnSEARCH STRATEGYnWe searched The Cochrane Skin Group Specialised Register (to March 2006), The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2006), MEDLINE (2003 to March 2006), EMBASE (2003 to March 2006), LILACS (to March 2006), PsycINFO (1806 to March 2006), AMED (1985 to March 2006), ISI Web of Science (March 2006), www.controlled-trials.com, www.clinicaltrials.gov and www.nottingham.ac.uk/ongoingskintrials (March 2006). Pharmaceutical companies were contacted where appropriate for reviews or unpublished trials.nnnSELECTION CRITERIAnPeople who have atopic eczema as diagnosed by a doctor.nnnDATA COLLECTION AND ANALYSISnTwo independent authors carried out study selection and assessment of methodological quality.nnnMAIN RESULTSnWe found 9 RCTs involving a total of 421 participants of which 6 were studies of egg and milk exclusion (N=288), 1 was a study of few foods (N=85) and 2 were studies of an elemental diet (N=48). There appears to be no benefit of an egg and milk free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet compared to normal diet (RR 1.51, 95% CI 1.07 to 2.11) and change in surface area and severity score was significantly improved in the exclusion diet compared to the normal diet at the end of 6 weeks (MD 5.50,95% CI 0.19 to 10.81) and end of treatment (MD 6.10, 95% CI 0.06 to12.14). Methodological difficulties have made it difficult to interpret these studies. Poor concealment of randomisation allocation, lack of blinding and high dropout rates without an intention-to-treat analysis indicates that these studies should be interpreted with great caution.nnnAUTHORS CONCLUSIONSnThere may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs. Little evidence supports the use of various exclusion diets in unselected people with atopic eczema, but that may be because they were not allergic to those substances in the first place. Lack of any benefit may also be because the studies were too small and poorly reported. Future studies should be appropriately powered focusing on participants with a proven food allergy. In addition a distinction should be made between young children whose food allergies improve with time and older children/adults.

Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies.

Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.

Dietary supplements for established atopic eczema

BACKGROUNDnMany people with atopic eczema are reluctant to use the most commonly recommended treatments because they fear the long-term health effects. As a result, many turn to dietary supplements as a possible treatment approach, often with the belief that some essential ingredient is missing in their diet. Various supplements have been proposed, but it is unclear whether any of these interventions are effective.nnnOBJECTIVESnTo evaluate dietary supplements for treating established atopic eczema/dermatitis.Evening primrose oil, borage oil, and probiotics are covered in other Cochrane reviews.nnnSEARCH METHODSnWe searched the following databases up to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), ISI Web of Science, GREAT (Global Resource of EczemA Trials) database, and reference lists of articles. We searched ongoing trials registers up to April 2011.nnnSELECTION CRITERIAnRandomised controlled trials (RCTs) of dietary supplements for the treatment of those with established atopic eczema/dermatitis.nnnDATA COLLECTION AND ANALYSISnTwo authors independently screened the titles and abstracts, read the full text of the publications, extracted data, and assessed the risk of bias.nnnMAIN RESULTSnWe included 11 studies with a total of 596 participants. Two studies assessed fish oil versus olive oil or corn oil placebo. The following were all looked at in single studies: oral zinc sulphate compared to placebo, selenium versus selenium plus vitamin E versus placebo, vitamin D versus placebo, vitamin D versus vitamin E versus vitamins D plus vitamin E together versus placebo, pyridoxine versus placebo, sea buckthorn seed oil versus sea buckthorn pulp oil versus placebo, hempseed oil versus placebo, sunflower oil (linoleic acid) versus fish oil versus placebo, and DHA versus control (saturated fatty acids of the same energy value). Two small studies on fish oil suggest a possible modest benefit, but many outcomes were explored. A convincingly positive result from a much larger study with a publicly-registered protocol is needed before clinical practice can be influenced.nnnAUTHORS CONCLUSIONSnThere is no convincing evidence of the benefit of dietary supplements in eczema, and they cannot be recommended for the public or for clinical practice at present. Whilst some may argue that at least supplements do not do any harm, high doses of vitamin D may give rise to serious medical problems, and the cost of long-term supplements may also mount up.

Dietary exclusions for improving established atopic eczema in adults and children: systematic review

Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion (nu2003=u2003288), one was a study of few foods (nu2003=u200385) and two were studies of an elemental diet (nu2003=u200348). There appears to be no benefit of an egg‐ and milk‐free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few‐foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg‐free diet in infants with suspected egg allergy who have positive specific IgE to eggs – one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07–2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6u2003weeks (MD 5.50, 95% CI 0.19–10.81) and end of treatment (MD 6.10, 95% CI 0.06–12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.