Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.

BACKGROUND: Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases. OBJECTIVES: 1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs. METHODS: We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity). RESULTS: 8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved. CONCLUSIONS: ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.

A SARS-CoV-2 outbreak in a plastics manufacturing plant.

BACKGROUND: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England. METHODS: Between 23rd March and 13th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors. RESULTS: While ventilation, indicated using real-time CO2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure. CONCLUSIONS: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted.

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Transmission and Control of SARS-CoV-2 in the Food Production Sector: A Rapid Narrative Review of the Literature.

This review aimed to provide an overview of the literature assessing the extent of COVID-19 transmission in the food processing sector along with the risk factors associated with COVID-19 infection/mortality rates in this setting, and the preventive measures used to reduce transmission. An electronic search was conducted using scientific databases, including Web of Science, OVID, PubMed and MedRxiv. The search strategy identified 26 papers that met the inclusion criteria. Six of these studies were based in the UK and the country with the most papers was the USA, with a total of nine papers. Findings showed some evidence of a high transmission level of SARS-CoV-2 within some areas of the food production sector. Risk factors associated with the spread included ethnicity, poor ventilation, lack of social distancing and lack of sick pay. The preventative measures included/recommended were social distancing, testing, adequate ventilation, cleaning regimes and access to PPE. Additional research focusing on the food production sector could show the potential variations in transmission and risk between each sub-sector. Future research focusing on the application of various preventative measures and their efficacy by sub-sector would be beneficial, while further qualitative research could help provide in-depth information regarding knowledge gaps.

Duration of protection of CoronaVac plus heterologous BNT162b2 booster in the Omicron period in Brazil.

To date, no information has been published on the effectiveness of inactivated whole-virus COVID-19 vaccines plus heterologous booster against symptomatic infection and severe outcomes (hospitalization or death) during the dominance of the SARS-CoV-2 Omicron variant period. We evaluated the vaccine effectiveness (VE) of CoronaVac plus BNT162b2 booster during the period of dominance of the Omicron variant in Brazil (January to April 2022). Using a test-negative design, we analysed data for 2,471,576 individuals tested during the Omicron variant's dominant period using a nationally linked database from Brazil. Compared to unvaccinated, vaccinees maintained protection against severe outcomes, with an estimated VE of 84.1% (95% CI:83.2-84.9) at more than 120 days after BNT162b2 booster. Furthermore, while we detected a high level of protection against severe outcomes for individuals up to 79 years old, waning was observed for individuals aged ≥80 years, with VE decreasing from 81.3% (95% CI:77.9-84.2) at 31-60 days to 72.9% (95% CI:70.6-75.1) at 120 days or more after the booster dose. However, no significant protection against symptomatic infection was observed at this time period. In conclusion, except for individuals aged ≥80 years, CoronaVac plus a BNT162b2 booster dose offered high and durable protection against severe outcomes due to Omicron.

Association Between Common Infections and Incident Post-Stroke Dementia: A Cohort Study Using the Clinical Practice Research Datalink.

PURPOSE: To investigate the association between common infections and post-stroke dementia in a UK population-based cohort. MATERIALS AND METHODS: A total of 60,392 stroke survivors (51.2% male, median age 74.3 years, IQR 63.9-82.4 years) were identified using primary care records from the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) with no history of dementia. Primary exposure was any GP-recorded infection (lower respiratory tract infection (LRTI), urinary tract infection (UTI) requiring antibiotics, skin and soft tissue infection requiring antibiotics) occurring after stroke. The primary outcome was incident all-cause dementia recorded in primary care records. In sensitivity analyses, we restricted to individuals with linked hospital records and expanded definitions to include ICD-10 coded hospital admissions. We used multivariable Cox regression to investigate the association between common infections and dementia occurring from 3 months to 5 years after stroke. RESULTS: Of 60,392 stroke survivors, 20,969 (34.7%) experienced at least one infection and overall 4512 (7.5%) developed dementia during follow-up. Early dementia (3 months to 1-year post-stroke) risk was increased in those with at least one GP-recorded infection (HR 1.44, 95% CI 1.21-1.71), with stronger associations when hospitalised infections were included (HR 1.84, 95% CI 1.58-2.14). Late dementia (1-5 years) was only associated with hospitalised, but not with GP-recorded, infections. CONCLUSION: There was evidence of an association between common infections and post-stroke dementia, strongest in the 3-12 months following stroke. Better understanding of this relationship could help inform knowledge of pathways to dementia post-stroke and targeting of preventive interventions.

Clinical profile of predefined asthma phenotypes in a large cohort of UK primary care patients (Clinical Practice Research Datalink).

BACKGROUND: Distinct asthma phenotypes have previously been suggested, including benign asthma, atopic asthma and obese non-eosinophilic asthma. This study aims to establish if these phenotypes can be identified using data recorded in primary care clinical records and reports on patient characteristics and exacerbation frequency. METHODS: A population-based cohort study identified 193,999 asthma patients in UK primary care from 2007 to 2017. We used linked primary and secondary care data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Patients were classified into predefined phenotypes or included in an asthma "not otherwise specified" (NOS) group. We used negative binomial regression to calculate the exacerbation rates and adjusted rate ratios. Rate ratios were further stratified by asthma treatment step. RESULTS: In our cohort, 3.9% of patients were categorized as benign asthma, 28.6% atopic asthma and 4.8% obese non-eosinophilic asthma. About 62.7% of patients were asthma NOS, including asthma NOS without treatment (10.4%), only on short-acting beta agonist (6.1%) and on maintenance treatment (46.2%). Crude severe exacerbation rates per 1,000 person-years were lowest for benign asthma (106.8 [95% CI: 101.2-112.3]) and highest for obese non-eosinophilic asthma (469.0 [451.7-486.2]). Incidence rate ratios for all phenotype groups decreased when stratified by treatment step but remained raised compared to benign asthma. CONCLUSION: Established phenotypes can be identified in a general asthma population, although many patients did not fit into the specific phenotypes which we studied. Phenotyping patients and knowledge of asthma treatment step could help anticipate clinical course and therefore could aid clinical management but is only possible in a minority of primary care patients based on current phenotypes and electronic health records (EHRs).

Global prevention and control of NCDs: Limitations of the standard approach.

The five-target '25 × 25' strategy for tackling the emerging global epidemic of non-communicable diseases (NCDs) focuses on four diseases (CVD, diabetes, cancer, and chronic respiratory disease), four risk factors (tobacco, diet and physical activity, dietary salt, and alcohol), and one cardiovascular preventive drug treatment. The goal is to decrease mortality from NCDs by 25 per cent by the year 2025. The 'standard approach' to the '25 × 25' strategy has the benefit of simplicity, but also has major weaknesses. These include lack of recognition of: (i) the fundamental drivers of the NCD epidemic; (ii) the 'missing NCDs', which are major causes of morbidity; (iii) the 'missing causes' and the 'causes of the causes'; and (iv) the role of health care and the need for integration of interventions.

IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

Which factors account for the ethnic inequalities in stage at diagnosis and cervical cancer survival in New Zealand?

OBJECTIVE: There are substantial ethnic inequalities in stage at diagnosis and cervical cancer survival in New Zealand. We assessed what proportions of these differences were due to screening history (for the analyses of late stage diagnosis), stage at diagnosis (for the analyses of survival), comorbid conditions (for the analyses of survival), and travel time to the nearest General Practitioner and cancer centre. METHODS: The study involved 1594 cervical cancer cases registered during 1994-2005. We used G-computation to assess the validity of the estimates obtained by standard logistic regression methods. RESULTS: Maori women had a higher risk of late stage diagnosis compared with 'Other' (mainly European) women (odds ratio (OR) = 2.71; 95% confidence interval 1.98, 3.72); this decreased only slightly (OR 2.39; 1.72, 3.30) after adjustment for screening history, and travel time to the nearest General Practitioner and cancer centre. In contrast, the (non-significantly) elevated risk in Pacific women (1.39; 0.76, 2.54) disappeared almost completely when adjusted for the same factors (1.06; 0.57, 1.96). The hazard ratio of mortality for cervical cancer for Maori women was 2.10 (1.61, 2.73) and decreased to 1.45 (1.10, 1.92) after adjustment for stage at diagnosis, comorbid conditions, and travel time to the nearest General Practitioner and cancer centre; the corresponding estimates for Pacific women were 1.96 (1.23, 3.13) and 1.55 (0.93, 2.57). The G-computation analyses gave similar findings. CONCLUSIONS: The excess relative risk of late stage diagnosis in Maori women remains largely unexplained, while more than half of the excess relative risk of mortality in Maori and Pacific women is explained by differences in stage at diagnosis and comorbid conditions.

Pure laparoscopic en bloc left hemihepatectomy and caudate lobe resection in patients with intrahepatic cholangiocarcinoma.

INTRODUCTION: There is an ongoing debate on whether it is safe to push the boundaries and widen the indications of laparoscopic liver surgery after careful patient selection. We report 2 cases of pure laparoscopic en bloc left hemihepatectomy and caudate lobe resection for intrahepatic cholangiocarcinoma (ICC). METHODS: The first patient (a 79-year old) had an ICC affecting segments 2, 3, and 4 of the liver with dilatation of segment 1 ducts at preoperative imaging. The second patient (an 81-year old) had an ICC affecting segments 2, 3 with local invasion of segment 1. Both patients underwent pure laparoscopic left hemihepatectomy and caudate lobe resection. RESULTS: The first patient's operative time was 360 minutes and blood loss was 390 mL. Postoperative hospital stay was 8 days. The definitive histology was as follows: pT1 ICC (25 mm in maximal diameter), with 20 mm free resection margin. The second patient's operative time was 310 minutes and blood loss was 300 mL. Postoperative hospital stay was 4 days. The definitive histology was as follows: T1 ICC (49 mm in maximal diameter) with 10 mm free resection margin. The first patient was disease free 12 months after surgery. The second patient died 11 months after surgery of metastatic disease. CONCLUSION: Pure laparoscopic left hemihepatectomy and caudate lobectomy for ICC may be feasible and safe. This is, however, a very complex procedure requiring extensive experience in laparoscopic liver surgery and careful patient selection to optimize surgical outcome. To our knowledge, this is the first systematic description of a pure laparoscopic en bloc left hemihepatectomy and caudate lobe resection for ICC.

Can bacterial endotoxin exposure reverse atopy and atopic disease?

Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to downregulate pre-existing airway eosinophilia and hyperreactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema.