Risk factors for SARS-CoV-2 infection at a UK electricity-generating company: a test-negative design case-control study.

OBJECTIVES: Identify workplace risk factors for SARS-CoV-2 infection, using data collected by a UK electricity-generating company. METHODS: Using a test-negative design case-control study, we estimated the OR of infection by job category, site, test reason, sex, vaccination status, vulnerability, site outage and site COVID-19 weekly risk rating, adjusting for age, test date and test type. RESULTS: From an original 80 077 COVID-19 tests, there were 70 646 included in the final analysis. Most exclusions were due to being visitor tests (5030) or tests after an individual first tested positive (2968).Women were less likely to test positive than men (OR=0.71; 95% CI 0.58 to 0.86). Test reason was strongly associated with positivity and although not a cause of infection itself, due to differing test regimes by area, it was a strong confounder for other variables. Compared with routine tests, tests due to symptoms were highest risk (94.99; 78.29 to 115.24), followed by close contact (16.73; 13.80 to 20.29) and broader-defined work contact 2.66 (1.99 to 3.56). After adjustment, we found little difference in risk by job category, but some differences by site with three sites showing substantially lower risks, and one site showing higher risks in the final model. CONCLUSIONS: In general, infection risk was not associated with job category. Vulnerable individuals were at slightly lower risk, tests during outages were higher risk, vaccination showed no evidence of an effect on testing positive, and site COVID-19 risk rating did not show an ordered trend in positivity rates.

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study.

BACKGROUND: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. METHODS: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993-95), ISAAC Phase III (2001-03), or both. We included individuals from two age groups (children aged 6-7 years and adolescents aged 13-14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. FINDINGS: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993-2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (-0·37, 95% CI -0·69 to -0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (-1·37, -2·47 to -0·27], in children and -1·67, -2·70 to -0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. INTERPRETATION: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. FUNDING: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III.

The burden of asthma, hay fever and eczema in adults in 17 countries: GAN Phase I study.

AIMS: Asthma, hay fever and eczema are three common chronic conditions. There have been no recent multi-country data on the burden of these three conditions in adults; the aims of this study are to fill this evidence gap. METHODS: The Global Asthma Network Phase I is a multi-country cross-sectional population-based study using the same core methodology as the International Study of Asthma and Allergies in Childhood Phase III. It provides data on the burden of asthma, hay fever and eczema in children and adolescents, and, for the first time, in their parents/guardians. RESULTS: Data were available from 193 912 adults (104 061 female; mean±sd age 38±7.5 years) in 43 centres in 17 countries. The overall prevalence (range) of symptoms was 6.6% (0.9-32.7%) for current wheeze, 4.4% (0.9-29.0%) for asthma ever, 14.4% (2.8-45.7%) for hay fever ever and 9.9% (1.6-29.5%) for eczema ever. Centre prevalence varied considerably both between countries and within countries. There was a moderate correlation between hay fever ever and asthma ever, and between eczema ever and hay fever ever at the centre level. There were moderate to strong correlations between indicators of the burden of disease reported in adults and the two younger age groups. CONCLUSION: We found evidence for a substantial burden of asthma, hay fever ever and eczema ever in the countries examined, highlighting the major public health importance of these diseases. Prevention strategies and equitable access to effective and affordable treatments for these three conditions would help mitigate the avoidable morbidity they cause.

The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study.

AIMS: There have been no worldwide standardised surveys of prevalence and severity of asthma, rhinoconjunctivitis and eczema in school children for 15 years. The present study aims to provide this information. METHODS: Following the exact International Study of Asthma and Allergies in Childhood (ISAAC) methodology (cross-sectional questionnaire-based survey), Global Asthma Network (GAN) Phase I was carried out between 2015 and 2020 in many centres worldwide. RESULTS: The study included 157 784 adolescents (13-14 years of age) in 63 centres in 25 countries and 101 777 children (6-7 years of age) in 44 centres in 16 countries. The current prevalence of symptoms, respectively, was 11.0% and 9.1% for asthma, 13.3% and 7.7% for rhinoconjunctivitis and 6.4% and 5.9% for eczema. The prevalence of asthma ever was 10.5% and 7.6%, hay fever ever was 15.2% and 11.1% and eczema ever was 10.6% and 13.4%, respectively. Centres in low or lower middle gross national income countries (LICs or LMICs) had significantly lower prevalence of the three disease symptoms and diagnoses (except for hay fever). In children, the prevalence of asthma and rhinoconjunctivitis symptoms was higher in boys, while the reverse occurred among adolescents. For eczema, while the prevalence among female adolescents was double that of males, there was no sex difference among children. Centre accounted for non-negligible variability in all disease symptoms (10-20%). CONCLUSION: The burdens of asthma, rhinoconjunctivitis and eczema vary widely among the limited number of countries studied. Although symptom prevalence is lower in LICs and LMICs, it represents a considerable burden everywhere studied.

Worldwide time trends in prevalence of symptoms of rhinoconjunctivitis in children: Global Asthma Network Phase I.

BACKGROUND: The Global Asthma Network (GAN), by using the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, has updated trends in prevalence of symptoms of childhood allergic diseases, including non-infective rhinitis and conjunctivitis ('rhinoconjunctivitis'), which is reported here. METHODS: Prevalence and severity of rhinoconjunctivitis were assessed by questionnaire among schoolchildren in GAN Phase I and ISAAC Phase I and III surveys 15-23 years apart. Absolute rates of change in prevalence were estimated for each centre and modelled by multi-level linear regression to compare trends by age group, time period and per capita national income. RESULTS: Twenty-seven GAN centres in 14 countries surveyed 74,361 13- to 14-year-olds ('adolescents') and 45,434 6- to 7-year-olds ('children'), with average response proportions of 90% and 79%, respectively. Many centres showed highly significant (p < .001) changes in prevalence of rhinoconjunctivitis in the past year ('current rhinoconjunctivitis') compared with ISAAC. The direction and magnitude of centre-level trends varied significantly (p < .001) both within and between countries. Overall, current rhinoconjunctivitis prevalence decreased slightly from ISAAC Phase III to GAN: -1.32% per 10 years, 95% CI [-2.93%, +0.30%] among adolescents; and -0.44% [-1.29%, +0.42%] among children. Together, these differed significantly (p < .001) from the upward trend within ISAAC. Among adolescents, centre-level trends in current rhinoconjunctivitis were highly correlated with those for eczema symptoms (rho = 0.72, p < .0001) but not with centre-level trends in asthma symptoms (rho = 0.15, p = .48). Among children, these correlations were positive but not significant. CONCLUSION: Symptoms of non-infective rhinoconjunctivitis among schoolchildren may no longer be on the increase globally, although trends vary substantially within and between countries.

Decline in renal function following intestinal transplant: is the die cast at 3 months?

INTRODUCTION: This study reports the incidence of chronic kidney disease (CKD) after intestinal transplant (IT) at a single, adult center in the United Kingdom. METHODS: A retrospective review of IT was undertaken. Methods of renal function assessment pre-transplant were compared. Post-transplant renal function and renal sparing strategies were analyzed. RESULTS: There was a 30% variation (p < .001) in estimated glomerular filtration rate (eGFR) and normalized GFR at assessment. In the first 3 months post-transplant, there was a 40% decline in eGFR which was irreversible. Liver inclusion was not protective with similar eGFR at 3 months (60 ml/min/1.73 m2 ) compared with IT (55 ml/min/1.73 m2 ). The rate of decline in the first 2 months was less in multivisceral transplant (MVT; 21%) than IT (52%) suggesting surgical magnitude did not contribute. Thirty percentage of recipients had acute cellular rejection post-transplant; 58% of these were in the first 3 months with a higher proportion in MVT (64%) than IT (27%). Tacrolimus exposure did not correlate with decline in renal function over the first 3 months post-transplant. CONCLUSION: We demonstrated a 40% decline in renal function within 3 months post-IT which was irreversible despite renal sparing strategies. Early intervention should be considered in patients with an acute decline in this post-transplant period.

Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation?

BACKGROUND: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication. OBJECTIVE: To explore the role of reverse causation in risk factors of asthma symptoms. METHODS: We compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels. RESULTS: There were 131 924 children aged 6-7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97-2.16), early life antibiotic use (1.65; 1.58-1.73) and open fire cooking (1.44; 1.26-1.65). In school level analyses, these risk factors again showed increased risks. There were 238 586 adolescents aged 13-14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75-1.86), cooking on an open fire (1.32; 1.22-1.43) and maternal tobacco use (1.23; 1.18-1.27). In school level analyses, these risk factors again showed increased risks. CONCLUSIONS & CLINICAL RELEVANCE: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation.

Potential asthma risk factors do not account for global asthma symptom prevalence patterns and time trends in children and adolescents.

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) and the Global Asthma Network (GAN) conducted a series of global asthma prevalence surveys, between 1990 and 2020, in adolescents aged 13-14 and children aged 6-7 years. We used them to assess whether potential asthma risk factors explain global asthma symptom prevalence trends over this period. Method: We fitted mixed-effects linear regression models to estimate associations between centre-level risk factor prevalence and both the mid-point asthma symptom prevalence and the change per decade. We also estimated the 2019 asthma symptom prevalence across all included centres. Results: For adolescents, across 50 centres in 26 countries there was weak evidence that decreasing asthma prevalence over time was associated with regular fast-food consumption and frequent television viewing. However, frequent television viewing, along with heavy truck traffic, were associated with higher prevalence of asthma symptoms at the study mid-point. For children, across 41 centres in 21 countries, no risk factors were associated with time trends in asthma symptom prevalence, but truck traffic and paracetamol in the first year of life were associated with higher mid-point prevalence.We estimated the 2019 asthma symptom prevalence, across a total of 124 centres, to be 12.8% (11.4%, 14.2%) with little evidence of a difference by age. Low-income countries had lower prevalence (children 5.2% [2.5%, 7.8%], adolescents 5.3% [2.8%, 7.8%]), than lower-middle-, upper-middle- and high-income countries (all approximately 14-15%). Including risk factors in the models did not change the estimates. Conclusion: Potential asthma risk factors do not seem to explain the global prevalence patterns or time trends. Country income accounts for some of the differences, but the unexplained variation is very high.

Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.

Background: Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. Methods: We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Results: Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. Conclusions: ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.

A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

Exploring regression dilution bias using repeat measurements of 2858 variables in ≤49 000 UK Biobank participants.

BACKGROUND: Measurement error in exposures and confounders can bias exposure-outcome associations but is rarely considered. We aimed to assess random measurement error of all continuous variables in UK Biobank and explore approaches to mitigate its impact on exposure-outcome associations. METHODS: Random measurement error was assessed using intraclass correlation coefficients (ICCs) for all continuous variables with repeat measures. Regression calibration was used to correct for random error in exposures and confounders, using the associations of red blood cell distribution width (RDW), C-reactive protein (CRP) and 25-hydroxyvitamin D [25(OH)D] with mortality as illustrative examples. RESULTS: The 2858 continuous variables with repeat measures varied in sample size from 109 to 49 121. They fell into three groups: (i) baseline visit [529 variables; median (interquartile range) ICC = 0.64 (0.57, 0.83)]; (ii) online diet by 24-h recall [22 variables; 0.35 (0.30, 0.40)] and (iii) imaging measures [2307 variables; 0.85 (0.73, 0.94)]. Highest ICCs were for anthropometric and medical history measures, and lowest for dietary and heart magnetic resonance imaging.The ICCs (95% confidence interval) for RDW, CRP and 25(OH)D were 0.52 (0.51, 0.53), 0.29 (0.27, 0.30) and 0.55 (0.54, 0.56), respectively. Higher RDW and levels of CRP were associated with higher risk of all-cause mortality, and higher concentration of 25(OH)D with lower risk. After correction for random measurement error in the main exposure, the associations all strengthened. Confounder correction did not influence estimates. CONCLUSIONS: Random measurement error varies widely and is often non-negligible. For UK Biobank we provide relevant statistics and adaptable code to help other researchers explore and correct for this.

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

Women in gastroenterology: the UK trainee experience.

Introduction: Compared with other medical specialties, there are lower numbers of female trainees and lower rates of flexible working in gastroenterology. This study aims to examine the experience of male and female trainees to understand specialty demographics and the experience of training. Methods: Gastroenterology training data were obtained from the British Society of Gastroenterology (BSG) trainee surveys from 2014, 2018 and 2020, and from the Royal College of Physicians Medical Workforce unit between 2011 and 2019. Data on endoscopy measures from 2011 to 2021 were obtained from the Joint Advisory Group (JAG) on gastrointestinal endoscopy, including the JAG Endoscopy training system and the National Endoscopy Database. Data were segregated and compared by gender. Results: The percentage of female gastroenterology trainees remains at around 40%, largely unchanged over the previous decade. From the BSG trainee survey, 29.5% of women have flexible working patterns compared with 2.6% of men (p<0.001), which is lower than other medical specialties. Less than half of female trainees felt confident about their job prospects once they qualify. A greater proportion of male than female trainees achieved provisional colonoscopy certification during training (55% vs 45%, p=0.005) and female trainees took longer to certify than male trainees (63 months vs 56 months, p=0.004). The total length of training time from primary medical qualification to consultancy was the same for men and women. Conclusion: Changes must be addressed from a national and institutional level to address equitable access to national training programmes and equality of outcome for male and female trainees.

Global Asthma Network Phase I Surveillance: Geographical Coverage and Response Rates.

Background-The Global Asthma Network (GAN) Phase I is surveying school pupils in high-income and low- or middle-income countries using the International Study of Asthma and Allergies in Childhood (ISAAC) methodology. Methods-Cross-sectional surveys of participants in two age groups in randomly selected schools within each centre (2015-2020). The compulsory age group is 13-14 years (adolescents), optionally including parents or guardians. Six to seven years (children) and their parents are also optional. Adolescents completed questionnaires at school, and took home adult questionnaires for parent/guardian completion. Children took home questionnaires for parent/guardian completion about the child and also adult questionnaires. Questions related to symptoms and risk factors for asthma and allergy, asthma management, school/work absence and hospitalisation. Results-53 centres in 20 countries completed quality checks by 31 May 2020. These included 21 centres that previously participated in ISAAC. There were 132,748 adolescents (average response rate 88.8%), 91,802 children (average response rate 79.1%), and 177,622 adults, with >97% answering risk factor questions and >98% answering questions on asthma management, school/work absence and hospitalisation. Conclusion-The high response rates achieved in ISAAC have generally been maintained in GAN. GAN Phase I surveys, partially overlapping with ISAAC centres, will allow within-centre analyses of time-trends in prevalence.

Comparison of individual-level and population-level risk factors for rhinoconjunctivitis, asthma, and eczema in the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three.

BACKGROUND: Symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in children cluster at both the individual and population levels. OBJECTIVES: To assess individual-level and school-level risk factors for symptoms of rhinoconjunctivitis and compare them to corresponding associations with symptoms of asthma and eczema in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: We studied 116,863 children aged 6-7 years from 2163 schools in 59 centres and 22 countries and 224,436 adolescents aged 13-14 years from 2037 schools in 97 centres in 41 countries. Multilevel logistic regression models were fitted with random intercepts for school, centre, and country, adjusting for sex and maternal education at the child level. Associations between symptoms and a range of lifestyle and environmental risk factors were assessed for both the child's exposure and mean exposure at the school. Models were fitted for rhinoconjunctivitis, asthma, and eczema singly (unimorbidity) and for combinations of these conditions (multimorbidity). RESULTS: Generally, associations between symptoms and exposures at the school level were similar in direction and magnitude to those at the child level. Associations with multimorbidity were stronger than for unimorbidity, particularly in individuals with symptoms of all three diseases, but risk factor associations found in conventional single disease analyses persisted among children with only one condition, after excluding multimorbid groups.Comparisons of individuals with only one disease showed that many risk factor associations were consistent across the three conditions. More strongly associated with asthma were low birthweight, cat exposure in infancy, and current maternal smoking. Current paracetamol use was more strongly associated with asthma and rhinoconjunctivitis than eczema. Breastfeeding was more strongly associated with eczema than asthma or rhinoconjunctivitis.The direction and magnitude of most risk factor associations were similar in affluent and non-affluent countries, although notable exceptions include farm animal contact in infancy and larger sibships, which were associated with increased risk of rhinoconjunctivitis in non-affluent countries but reduced risk in affluent countries. In both age groups, current paracetamol use increased risk of each disease to a greater extent in affluent countries than in non-affluent countries. Effects of paracetamol and antibiotics in infancy were more consistent between richer and poorer settings. CONCLUSIONS: Most of the environmental and lifestyle correlates of rhinoconjunctivitis, asthma and eczema in childhood display similarity across the three conditions, even in less affluent settings where allergic sensitisation is less likely to explain the concordant epidemiological patterns. TRIAL REGISTRATION: Not applicable.

Simultaneous Intestinal and Kidney Transplantation in Adults.

Aim of the study: Intestinal transplantation (IT) is a life-saving procedure for carefully selected patients with intestinal failure. We evaluated patients who had undergone simultaneous intestinal and kidney transplantation (SIKT) to determine whether UK guidelines for inclusion of a renal allograft (dialysis dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m2) are justified. Methods: A single centre analysis was undertaken of adults undergoing IT at the Cambridge Transplant Centre between December 2007 and January 2016. A prospectively maintained database was used to identify SIKT recipients and determine outcomes. Results: Over this period, 63 intestinal transplants were performed. Seven (11.1%) recipients received a SIKT. Five were pre-dialysis (median eGFR 29 ml/min/1.73 m2, range 16-36 ml/min/1.73 m2). One recipient was on dialysis, and one needed bilateral nephrectomy at transplant. There were no primary kidney allograft failures and at three months, the median eGFR (55 ml/min/1.73 m2 range 39-124) was similar to recipients of IT alone (median eGFR 56 ml/min/1.73 m2 range 17-143 ml/min/1.73 m2). Two recipients required dialysis due to sepsis related kidney injury and died from multi-organ failure (20 and 63 months). Two died with a functioning renal transplant (10 and 15 months). The remaining three patients are alive at follow up (12-96 months) with an eGFR of 20-45 ml/min/1.73 m2. Conclusion: Patients with significant renal impairment (eGFR <45 ml/min/1.73 m2), and receiving dialysis may benefit from SIKT. Patient survival and renal function are broadly comparable to those undergoing IT alone. Further studies are required to justify allocation of a kidney to this complex high risk group.

Are Environmental Factors for Atopic Eczema in ISAAC Phase Three due to Reverse Causation?

Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6-7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37-1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10-2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34-1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21-1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00-1.82 and OR = 0.94, 95% CI = 0.69-1.28, respectively). At ages 13-14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51-1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33-1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84-3.59 and OR = 2.38, 95% CI = 1.52-3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27-1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07-1.82). Most individual- and school-level effects were consistent, tending to exclude reverse causation.

Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review.

Introduction: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. Presentation of case: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. Discussion: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. Conclusion: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor.