Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Recurrence-free survival after total thyroidectomy and lobectomy in patients with papillary thyroid microcarcinoma.

PURPOSE: The incidence of papillary thyroid microcarcinoma is increasing. We evaluated the recurrence-free survival following total thyroidectomy and lobectomy to identify the optimal surgical choice. METHODS: A meta-analysis was performed using the National Library of Medicine and the National Institutes of Health PubMed database to identify eligible studies. Summary 5- and 10-year RFS estimates after TT versus LT were calculated using random effects models. RESULTS: The literature search yielded 1117 studies (1990-2019). Nine studies met the inclusion criteria comprising 10,186 total thyroidectomy and 11,408 lobectomy patients. The 5-year recurrence-free survival was 98% [95% confidence interval (CI) 97-99%] after total thyroidectomy and 97% (95% CI 96-99%) after lobectomy, based on eight studies (9421 total thyroidectomy and 11,283 lobectomy patients); the 10-year recurrence-free survival was 95% (95% CI 92-98%) after total thyroidectomy and 92% (95% CI 86-96%) after lobectomy, based on eight studies (total thyroidectomy = 10,100, lobectomy = 11,389 patients). CONCLUSION: The present meta-analysis demonstrates excellent, long-term recurrence-free survival following both total thyroidectomy and lobectomy surgery in patients with papillary thyroid microcarcinoma. The analysis also suggests that patients undergoing total thyroidectomy trended toward a slightly better long-term 10-year recurrence-free survival in comparison to patients undergoing lobectomy, a finding of potential, clinical significance in the management decision-making process.

Indoor tanning prevalence after the International Agency for Research on Cancer statement on carcinogenicity of artificial tanning devices: systematic review and meta-analysis.

BACKGROUND: Exposure to artificial tanning devices is carcinogenic to humans, and government regulations to restrict or ban indoor tanning appear to be increasing. OBJECTIVES: We evaluated changes in the international prevalence of indoor tanning among adolescents and adults after artificial tanning devices were classified as carcinogenic by the International Agency for Research on Cancer (IARC) in 2009. METHODS: Systematic searches in PubMed and Web of Science databases were undertaken. Overall, 43 studies reporting 'ever' or 'past-year' indoor tanning exposure after 2009 were identified. We used metaregression analysis to evaluate the prevalence of indoor tanning over time. Random effects meta-analysis was used to summarize the prevalence of indoor tanning in adolescents and adults according to sex, region and presence of age prohibitions. RESULTS: Global prevalence of indoor tanning in adolescents for 2013-2018 was 6·5% [95% confidence interval (CI) 3·3-10·6], 70% lower than the 22·0% (95% CI 17·2-26·8) prevalence for 2007-2012. Among adults, the prevalence was 10·4% (95% CI 5·7-16·3) for 2013-2018, a decrease of 35% from 18·2% for 2007-2012. Since 2009, the overall past-year prevalence among adolescents was 6·7% (95% CI 4·4-9·6) and 12·5% (95% CI 9·5-15·6) among adults. The prevalence of tanning indoors in the past year was similar in North America (adults, 12·5%; adolescents, 7·6%) and Europe (adults, 11·1%; adolescents, 5·1%). In 2009, three countries had regulations restricting indoor tanning, compared with 26 countries today. CONCLUSIONS: Prevalence of indoor tanning has declined substantially and significantly in adolescents and adults since the 2009 IARC statement, reflecting the rise in regulations that limit this source of unnecessary exposure to carcinogenic ultraviolet radiation. What is already known about this topic? Indoor tanning is associated with an increased risk of melanoma. A meta-analysis of worldwide indoor tanning prevalence for 1986-2012 found a past-year prevalence of 18% in adolescents and 14% in adults, with higher prevalences during the period 2007-2012. Policies to regulate indoor tanning began to be implemented across the globe in 2009. Only one study carried out in the U.S.A. has evaluated the efficacy of such policies in reducing indoor tanning prevalence. What does this study add? For the period 2013-2018, we found indoor tanning prevalences of 6·7% in adolescents and 11·9% in adults. This implies a reduction in indoor tanning use of 70% in adolescents and 35% in adults during the last 10 years. Our study encourages policy makers to strengthen indoor tanning regulations that reduce sunbed use among the general population in order to produce maximum public health benefit.

Human health in relation to exposure to solar ultraviolet radiation under changing stratospheric ozone and climate.

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.

Delay from symptom onset to treatment start among tuberculosis patients in England, 2012-2015.

Improving access to tuberculosis (TB) care and ensuring early diagnosis are two major aims of the WHO End TB strategy and the Collaborative TB Strategy for England. This study describes risk factors associated with diagnostic delay among TB cases in England. We conducted a retrospective cohort study of TB cases notified to the Enhanced TB Surveillance System in England between 2012 and 2015. Diagnostic delay was defined as more than 4 months between symptom onset and treatment start date. Multivariable logistic regression was used to identify demographic and clinical factors associated with diagnostic delay. Between 2012 and 2015, 22 422 TB cases were notified in England and included in the study. A third (7612) of TB cases had a diagnostic delay of more than 4 months. Being female, aged 45 years and older, residing outside of London and having extra-pulmonary TB disease were significantly associated with a diagnostic delay in the multivariable model (aOR = 1.2, 1.2, 1.2, 1.3, 1.8, respectively). This study identifies demographic and clinical factors associated with diagnostic delay, which will inform targeted interventions to improve access to care and early diagnosis among these groups, with the ultimate aim of helping reduce transmission and improve treatment outcomes for TB cases in England.

Online market research panel members as controls in case-control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK.

Established methods of recruiting population controls for case-control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case-control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.

Investigation of a national outbreak of STEC Escherichia coli O157 using online consumer panel control methods: Great Britain, October 2014.

In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2-92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0-157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.

Impact of an outright ban on the availability of commercial tanning services in Victoria, Australia.

Australian states have introduced an outright ban on commercial artificial tanning sunbeds. This was based on evidence from systematic reviews affirming a strong association between tanning bed use and increased risk of melanoma. The implementation of the ban provides an opportunity to assess the effectiveness of the legislation in preventing access to artificial UV radiation. Compliance with the ban has been enforced and monitored by government departments. We additionally monitored online tanning bed advertisements before and after the ban, showing a decline over time in the number of sunbeds advertised for sale on gumtree.com.au and ebay.com.au, from a peak of 115 advertisements in May 2014 to 50 or fewer per month from February 2015. There was also an increase in advertised price, with the percentage of sunbeds offered in Victoria on gumtree.com.au at higher than $2 000 increasing from around 25% between January and June 2014 to 65% in the quarter following the introduction of the ban. Advertisements on gumtree.com.au from individuals wishing to access a sunbed in a private home in Victoria increased from only isolated instances in the months immediately prior to the ban, to between 25 and 77 advertisements per month in the quarter following the ban. In summary, the introduction of an outright ban of commercial sunbeds has achieved a dramatic reduction in the availability of harmful artificial UV radiation sources in Australia. Long-term benefits to the health of the population and a reduction in costs to the health system are expected to result.

Cutaneous Mycobacterium chelonae infection in Edinburgh and the Lothians, South-East Scotland, U.K.

BACKGROUND: We reviewed all cases of Mycobacterium chelonae infection seen in our department between 1 January 2008 and 31 December 2012. OBJECTIVES: To review the epidemiology, clinical features and management of cutaneous M. chelonae in South-East Scotland, and to compare prevalence data with the rest of Scotland. METHODS: The Scottish Mycobacteria Reference Laboratory database was searched for all cases of cutaneous mycobacterial infections. RESULTS: One hundred and thirty-four cases of cutaneous mycobacterial infection were recorded. Sixty-three were tuberculous; of the remaining 71, M. chelonae was the most common nontuberculous organism (27 cases). National Health Service (NHS) Lothian Health Board was the area with highest incidence in the Scotland (12 cases). Three main groups of patients in the NHS Lothian Health Board contracted M. chelonae: immunosuppressed patients (n = 6); those who had undergone tattooing (n = 4); and others (n = 2). One case is, we believe, the first report of M. chelonae cutaneous infection associated with topical corticosteroid immunosuppression. The majority of patients were treated with clarithromycin monotherapy. CONCLUSION: The most prevalent nontuberculous cutaneous mycobacterial organism in Scotland is M. chelonae. The prevalence of M. chelonae in Edinburgh and the Lothians compared with the rest of Scotland is disproportionately high, possibly owing to increased local awareness and established facilities for mycobacterial studies. Immunosuppression with prednisolone appears to be a major risk factor. The first outbreak of tattoo-related M. chelonae infection in the U.K. has been reported. Clinicians should be aware of mycobacterial cutaneous infection and ensure that diagnostic skin samples are cultured at the optimal temperatures.

Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014.

In January to February 2014, 16 hand, foot and mouth disease (HFMD) cases were identified in Edinburgh, United Kingdom. All presented with atypical features, with most (n=13) resembling eczema herpeticum or chickenpox. Coxsackievirus A6 (CV-A6) was identified in all the typed cases (n=11). As atypical forms of HFMD associated with CV-A6 are likely to emerge throughout Europe, clinicians should be alert to unusual clinical presentations of HFMD and virologists aware of effective diagnostic testing and enterovirus typing methods.

Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle.

Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies.

MRI may provide treatment outcome measures in neuromuscular conditions. The authors assessed MRI magnetisation transfer ratios (MTRs) in lower-limb musculature as markers of pathology in peripheral neuropathies and compared the findings with associated clinical data. Ten patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were compared with 10 healthy subjects. The MTR in the calf muscles was significantly lower than controls in the two patient groups (both p<0.001). The median MTRs (IQR) were 50.5(1.6) percentage units (p.u.) (control), 41.5(10.6) p.u. (CMT1A) and 39.3(8.7) p.u. (CIDP). Moreover, anterior lower leg MTR correlated strongly with strength of ankle dorsiflexion, measured with the Medical Research Council scale, in CIDP (ρ=0.88, p<0.001) and also in CMT1A (ρ=0.50, p<0.05), where MTR also showed an association with disease duration (ρ=-0.86, p<0.001). Short tau inversion recovery MRI of the same muscles showed abnormalities associated with regions of reduced MTR (p<0.001), and MTR was also reduced in other muscles otherwise deemed normal appearing (p<0.001), indicating that MTR may be more sensitive to muscle damaged by denervation than conventional MRI. The significant reductions in muscle MTR in peripheral neuropathies and the associated correlations with clinical measures indicate that MTR has potential as an imaging outcome measure in future therapeutic trials.

Running behind a tourist: leisure-related skin cancer prophylaxis.

The most important risk factor in the development of skin cancer is exposure to ultraviolet (UV) radiation. Cumulative lifetime UV radiation exposure has been shown to be most important in the pathogenesis of squamous cell carcinoma, whereas intermittent high-dose UV radiation exposure in childhood and adolescence may be more important in the aetiology of basal cell carcinoma and cutaneous malignant melanoma. Using established methodology and best available estimates on UV-related mortality and morbidity, it has been estimated that annually around 1·5 million disability-adjusted life years are lost through excessive exposure to UV radiation. Skin cancer is a significant health problem and its burden is such that it causes the health system more to treat than any other forms of cancer. Prevention is the key action in managing skin cancer at a population level. Investment in prevention programmes such as SunSmart encourages protective behaviours that will reduce the human and financial costs of skin cancer.

MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies.

Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot-Marie-Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm(2) for the CIDP group, 135.9 (46.5) mm(2) for the CMT1A group and 43.3 (19.9) mm(2) for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm(2). Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.

Double tensile twinning in a Mg-8Al-0.5Zn alloy.

The presence of deformation twinning in magnesium introduces significant challenges for predicting the bulk response of the material. In this work, we present results showing the presence of tensile twins formed within pre-existing tensile twins in samples deformed in compression at 77 K. Such double twins mirror the observation of double compression-tension twins previously observed. It is argued that the observed double twinning occurs due to the difficulty of non-basal slip at the low test temperature.

A Radiologic Grading System for Assessing the Radiographic Outcome of Treatment in Lymphatic and Lymphatic-Venous Malformations of the Head and Neck.

BACKGROUND AND PURPOSE: Two-thirds of lymphatic malformations in children are found in the head and neck. Although conventionally managed through surgical resection, percutaneous sclerotherapy has gained popularity. No reproducible grading system has been designed to compare sclerotherapy outcomes on the basis of radiologic findings. We propose an MR imaging-based grading scale to assess the response to sclerotherapy and present an evaluation of its interrater reliability. MATERIALS AND METHODS: A grading system was developed to stratify treatment outcomes on the basis of interval changes observed on MR imaging. By means of this system, 56 consecutive cases from our institution with formally diagnosed head and neck lymphatic malformations treated by sclerotherapy were retrospectively graded. Each patient underwent pre- and posttreatment MR imaging. Each study was evaluated by 3 experienced neuroradiologists. Interrater reliability was assessed using the Krippendorff α statistic, intraclass coefficient, and 2-way Spearman ρ correlation. RESULTS: The overall Krippendorff α statistic was 0.93 (95% CI, 0.89-0.95), denoting excellent agreement among raters. Intraclass coefficients with respect to consistency and absolute agreements were both 0.97 (95% CI, 0.96-0.98), illustrating low variability. Every combination of individual rater pairs demonstrated statistically significant (P < .01) linear Spearman ρ correlations, with values ranging from 0.90 to 0.95. CONCLUSIONS: The proposed radiographic grading scale demonstrates excellent interrater reliability. Adoption of this new scale can standardize reported outcomes following sclerotherapy for head and neck lymphatic malformation and may aid in the investigation of future questions regarding optimal management of these lesions.

Epidemiology of injuries among U18, U19, U21 and senior elite netball players.

Background: Despite a substantial body of literature on injuries among elite netball players in South Africa, no study reports on the timing and type of injuries and the reason for injuries. Objective: To determine the epidemiology of injuries in U18, U19, U21 and senior netball players in the Free State (FS), South Africa, over two consecutive netball seasons (2017/2018). Methods: An injury questionnaire was used to collect data on 96 eligible players. Results: A total of 48 injuries were reported. The profile of injuries revealed that 58% (n=28) of the injuries occurred during matches, 29% (n=14) during practice and 13% (n=6) during preseason training. Acute injuries accounted for 54% (n=26) of the total, while 46% (n=22) were overuse injuries. A third of all the injuries were re-injuries. The centre (C) position had the highest incidence of injuries in players (n=14; 29%). The ankle was the most frequently injured body part (n=18; 36%), followed by the lower leg and Achilles tendon (n=6; 13%) thus largely the ligaments and muscles. The overall incidence rate of injuries during match play was 33.9 injuries per 1 000 hours of match play. Conclusion: Preventative strategies should consist of ankle and lower leg strengthening and neuromuscular balance techniques. The focus should be on correct landing techniques, results of abrupt change of direction movements and short bursts of speed.

Physical and physiological profile of U18, U19, U21 and senior elite netball players.

Background: Physical and physiological profile data for elite netball players in South Africa and internationally are limited but are necessary for conditioning programme information. Objective: To determine the physical and physiological profiles of U18, U19, U21 and senior level elite netball players at provincial level in the Free State, South Africa. The information provided is by age group and playing position. The fitness of the players for South African and New Zealand netball is also given using the fitness normative data (norms). Methods: This cross-sectional, descriptive study consisted of 77 elite South African netball players. Anthropometric measurements were taken according to international standards. Fitness tests included the Star Execution Balance Test, standing broad jump, double- and single-leg vertical jump, Yo-Yo Intermittent Recovery Level 1(IR1) test, sprints over 5, 10 and 40 m, horizontal pull-ups and press-ups, the prone bridge test and anaerobic Octorepeater tests with 10 m and 20 m repeated shuttle sprints. In keeping with the descriptive nature of the study, descriptive statistics were calculated for numerical data by age group and playing position. Results: Players generally did not meet the accepted fitness standards in the following areas: press-ups (all age groups), horizontal pull-ups (senior and U21), standing broad jump (senior and U21), vertical squat jump (senior and U21), 5 m and 10 m sprints (senior and U21); anaerobic Octorepeater (senior players), and the aerobic Yo-Yo IR1 test (all age groups). Conclusion: Strength and conditioning coaches should develop training programmes to address fitness areas where players do not meet the international standards.