Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients. Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis.

BACKGROUND: Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform vaccination policies and the updating of pneumococcal vaccines. METHODS: We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by pneumococcal vaccine serotypes. We searched MEDLINE, EMBASE and PubMed from 1 January 1990 to 30 March 2021. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRD42020192002). FINDINGS: Twenty-eight studies were included (34,216 patients). In the period 1-5 years after introduction of childhood PCV10/13 immunisation, 18% of CAP cases (95% CI 13-24%) were attributable to pneumococcus, with 49% (43-54%) of pneumococcal CAP due to PCV13 serotypes. The estimated proportion of pneumococcal CAP was highest in one study that used 24-valent serotype-specific urinary-antigen detection (ss-UAD)(30% [28-31%]), followed by studies based on diagnostic serology (28% [24-33%]), PCR (26% [15-37%]), ss-UAD14 (17% [13-22%]), and culture alone (14% [10-19%]). A higher estimate was observed in Europe (26% [21-30%] than North America (11% [9-12%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods. INTERPRETATION: Non-invasive pneumococcal CAP and vaccine-type pneumococcal CAP remains a burden in older adults despite widespread introduction of pneumococcal infant immunisation. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking.

Spotlight influenza: Laboratory-confirmed seasonal influenza in people with acute respiratory illness: a literature review and meta-analysis, WHO European Region, 2004 to 2017.

BackgroundAcross the World Health Organization European Region, there are few estimates of the proportion of people seeking medical care for influenza-like illness or acute respiratory infections and who have laboratory-confirmed seasonal influenza infection.MethodsWe conducted a meta-analysis of data extracted from studies published between 2004 and 2017 and from sentinel data from the European surveillance system (TESSy) between 2004 and 2018. We pooled within-season estimates by influenza type/subtype, setting (outpatient (OP)/inpatient (IP)) and age group to estimate the proportion of people tested who have laboratory-confirmed and medically-attended seasonal influenza in Europe.ResultsIn the literature review, the pooled proportion for all influenza types was 33% (95% confidence interval (CI): 30-36), higher among OP 36% (95% CI: 33-40) than IP 24% (95% CI: 20-29). Pooled estimates for all influenza types by age group were: 0-17 years, 26% (22-31); 18-64 years, 41% (32-50); ≥ 65 years, 33% (27-40). From TESSy data, 33% (31-34) of OP and 24% (21-27) of IP were positive. The highest proportion of influenza A was in people aged 18-64 years (22%, 16-29). By subtype, A(H1N1)pdm09 was highest in 18-64 year-olds (16%, 11-21%) whereas A(H3N2) was highest in those ≥ 65 years (10%, 2-22). For influenza B, the highest proportion of infections was in those aged 18-64 years (15%, 9-24).ConclusionsLaboratory-confirmed influenza accounted for approximately one third of all acute respiratory infections for which medical care was sought during the influenza season.

Co-infection in critically ill patients with COVID-19: an observational cohort study from England.

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus.Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation.Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

Decline in Seasonal Influenza Vaccine Effectiveness With Vaccination Program Maturation: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence suggests that repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (PM; number of years since program inception) as a proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies. METHODS: We systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles and calculated pooled VE using an inverse-variance random-effects model. The primary outcome was pooled VE against all influenza. RESULTS: We included 72 articles from 11 931 citations. Across the 3 categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2), and influenza B. CONCLUSIONS: The evidence suggests that influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE.

Co-infections in people with COVID-19: a systematic review and meta-analysis.

OBJECTIVES: In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19. METHODS: We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. . RESULTS: Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92·2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74·7% versus 4%, 95% CI 1-9, I2= 91·7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62·3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections. CONCLUSIONS: A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.

Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stay.

Introduction. Every winter seasonal influenza and other viral respiratory infections increase pressure on the health services and are associated with nosocomial infection and morbidity.Aim. To compare provision of point-of-care (POC) testing with laboratory-based testing for influenza and RSV detection on an adult respiratory assessment unit to assess the impact on isolation practices and length of stay (LOS).Methodology. Prospective interrupted 'on-off' study in adults admitted to the respiratory unit between December 2018 and April 2019 with a suspected respiratory tract infection. Nasopharyngeal samples were tested using either the GeneXpert rapid POC test for influenza and RSV (on-period), or were sent to the laboratory for multiplex PCR testing against a panel of 12 respiratory viruses (off-period). Outcome measures were time to patient isolation for infection control, LOS and turnaround time from admission to test results.Results. Of 1145 patients evaluated, 755 were tested with POC and 390 with laboratory multiplex; a respiratory virus was identified in 164 (21.7 %) and 138 (35.4 %) patients respectively. A positive POC test was associated with a shorter time to isolation (mean difference 16.9 h, P<0.001), shorter LOS (mean difference 15.5 h, P=0.05,) and shorter turnaround time (mean difference 28.3 h, P<0.001), compared to laboratory testing.Conclusion. Use of GeneXpert POC testing for Flu/RSV is associated with rapid reporting of results with significant improvements in isolation practices and reductions in LOS.

Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis.

OBJECTIVES: Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. STUDY SELECTION AND DATA EXTRACTION: Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. DATA SYNTHESIS: We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31-6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09-2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51-4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day). CONCLUSIONS: Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern.

Corticosteroids as adjunctive therapy in the treatment of influenza.

BACKGROUND: Specific treatments for influenza are limited to neuraminidase inhibitors and adamantanes. Corticosteroids show evidence of benefit in sepsis and related conditions, most likely due to their anti-inflammatory and immunomodulatory properties. Although commonly prescribed for severe influenza, there is uncertainty over their potential benefits or harms. This is an update of a review first published in 2016. OBJECTIVES: To systematically assess the effectiveness and potential adverse effects of corticosteroids as adjunctive therapy in the treatment of influenza, taking into account differences in timing and doses of corticosteroids. SEARCH METHODS: We searched CENTRAL (2018, Issue 9), which includes the Cochrane Acute Respiratory infections Group's Specialised Register, MEDLINE (1946 to October week 1, 2018), Embase (1980 to 3 October 2018), CINAHL (1981 to 3 October 2018), LILACS (1982 to 3 October 2018), Web of Science (1985 to 3 October 2018), abstracts from the last three years of major infectious disease and microbiology conferences, and references of included articles. We also searched the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry on 3 October 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, and observational studies that compared corticosteroid treatment with no corticosteroid treatment for influenza or influenza-like illness. We did not restrict studies by language of publication, influenza subtypes, clinical setting, or age of participants. We selected eligible studies in two stages: sequential examination of title and abstract, followed by full text. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We pooled estimates of effect using a random-effects model, where appropriate. We assessed heterogeneity using the I2 statistic and assessed the certainty of the evidence using the GRADE framework. MAIN RESULTS: This updated review includes 30 studies (one RCT with two arms and 29 observational studies) with a total of 99,224 participants. We included 19 studies in the original review (n = 3459), all of which were observational, with 13 studies included in the meta-analysis for mortality. We included 12 new studies in this update (one RCT and 11 observational studies), and excluded one study in the original review as it has been superceded by a more recent analysis. Twenty-one studies were included in the meta-analysis (9536 individuals), of which 15 studied people infected with 2009 influenza A H1N1 virus (H1N1pdm09). Data specific to mortality were of very low quality, based predominantly on observational studies, with inconsistent reporting of variables potentially associated with the outcomes of interest, differences between studies in the way in which they were conducted, and with the likelihood of potential confounding by indication. Reported doses of corticosteroids used were high, and indications for their use were not well reported. On meta-analysis, corticosteroid therapy was associated with increased mortality (odds ratio (OR) 3.90, 95% confidence interval (CI) 2.31 to 6.60; I2 = 68%; 15 studies). A similar increase in risk of mortality was seen in a stratified analysis of studies reporting adjusted estimates (OR 2.23, 95% CI 1.54 to 3.24; I2 = 0%; 5 studies). An association between corticosteroid therapy and increased mortality was also seen on pooled analysis of six studies which reported adjusted hazard ratios (HRs) (HR 1.49, 95% CI 1.09 to 2.02; I2 = 69%). Increased odds of hospital-acquired infection related to corticosteroid therapy were found on pooled analysis of seven studies (pooled OR 2.74, 95% CI 1.51 to 4.95; I2 = 90%); all were unadjusted estimates, and we graded the data as of very low certainty. AUTHORS' CONCLUSIONS: We found one RCT of adjunctive corticosteroid therapy for treating people with community-acquired pneumonia, but the number of people with laboratory-confirmed influenza in the treatment and placebo arms was too small to draw conclusions regarding the effect of corticosteroids in this group, and we did not include it in our meta-analyses of observational studies. The certainty of the available evidence from observational studies was very low, with confounding by indication a major potential concern. Although we found that adjunctive corticosteroid therapy is associated with increased mortality, this result should be interpreted with caution. In the context of clinical trials of adjunctive corticosteroid therapy in sepsis and pneumonia that report improved outcomes, including decreased mortality, more high-quality research is needed (both RCTs and observational studies that adjust for confounding by indication). The currently available evidence is insufficient to determine the effectiveness of corticosteroids for people with influenza.

Influenza in long-term care facilities.

Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis.

BACKGROUND: The clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines. METHODS: We searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR)∗100. Narrative synthesis was undertaken where meta-analysis was not possible. RESULTS: We identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE=80%; 95% confidence interval [CI] 59-90%; unadjuvanted: VE=66%; 95% CI 47-78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14-82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18-64years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes. CONCLUSIONS: Adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in 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.

Clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin-resistant Staphylococcus aureus bloodstream infections.

Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

Interventions for non-metastatic squamous cell carcinoma of the skin.

BACKGROUND: Squamous cell carcinoma (SCC) is the second most common skin cancer, and is becoming increasingly common around the world. Left untreated, it may spread to other parts of the body, and, although the risk is low, it may ultimately lead to death. Surgical excision is the first line of treatment for most skin SCCs, although other forms of treatment are also used depending upon the nature and site of the tumour and individual participant factors. A multi-professional approach is therefore required for the management of people with this condition. OBJECTIVES: To assess the effects of treatments for primary non-metastatic squamous cell carcinoma of the skin. SEARCH STRATEGY: In February 2010 we searched for relevant trials in The Cochrane Skin Group Specialised Register, The Cochrane Library (Issue 1, 2010), MEDLINE, EMBASE, PsycINFO, AMED, LILACS, and the ongoing trials registries. SELECTION CRITERIA: We only included randomised controlled trials (RCTs) of interventions for primary SCC of the skin. Inclusion criteria were: adults with one or more histologically proven primary SCCs of the skin which had not metastasised. The primary outcome measures were time to recurrence one to five years after treatment, and quality of life. Secondary outcomes included early treatment failure within six months, number of adverse events by the end of treatment, aesthetic appearance as assessed by the participant and clinician, discomfort to the participant during and after treatment, and death. DATA COLLECTION AND ANALYSIS: Two authors (LL, FB-H) independently carried out study selection and assessment of methodological quality and data extraction. MAIN RESULTS: One trial involving 65 people was included. This compared the time to recurrence in participants with aggressive skin SCC who were randomised to receive either adjuvant 13-cis-retinoic acid and interferon alpha after surgery with or without radiation treatment, or no adjuvant therapy after their initial treatment. There was no significant difference in time to recurrence of tumour between the two groups (hazard ratio 1.08, 95% confidence intervals 0.43 to 2.72).Most studies identified from the searches were excluded as they were either uncontrolled case series, did not include participants with invasive primary SCC, or included only participants with recurrent or metastatic disease. AUTHORS' CONCLUSIONS: Little evidence from RCTs comparing the efficacy of different interventions for primary cutaneous SCCs exists. There is a clear need for well-designed randomised studies in order to improve the evidence base for the management of this condition.