Recommendations for implementing lung cancer screening with low-dose computed tomography in Europe

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Interaction of nontypable Haemophilus influenzae with human respiratory mucosa in vitro

One laboratory strain (SH9) (n = 12) and five clinical isolates of unencapsulated Haemophilus influenzae replicated from 10(4) to 10(8) cfu/ml over 24 h in an organ culture of human respiratory mucosa in which only the intact mucosal surface is exposed. By transmission electron microscopy (TEM), bacteria were not seen in association with normal respiratory epithelium, even after incubation for 24 h. Histology and TEM morphometry demonstrated patchy and occasionally confluent damage to epithelia at this time, with bacteria associated only with cells that were structurally damaged. Scanning electron microscopy revealed an increased quantity of mucus in infected preparations; H. influenzae were associated with mucus by 14 h of incubation and with damaged epithelial cells by 24 h. Fimbriation of H. influenzae increased buccal cell adherence but did not facilitate association with normal respiratory epithelium and failed to increase epithelial damage or association with damaged cells. Epithelial damage may be prerequisite for association of H. influenzae with respiratory epithelium in vitro.</p

Practical considerations for implementing an evidence-based policing approach in police operations: a case study

Through the lens of a real operation carried out at Greater Manchester Police to protect the business community from burglaries over the Christmas and New Year period in 2017/2018, this paper highlights the practical considerations in implementing an evidence-based approach in policing operations where there is a perceived immediate threat, risk and harm. Operation Guard was a force-wide operation that ran for four months (1st December 2017–30th March 2018 inclusive) across seven districts and eleven wards in Greater Manchester (UK), with the primary mandate of reducing Greater Manchester Police’s (GMP) commercial burglary crime volume. With the operation carrying a second aim of tactical delivery through an evidence-based policing methodology, representing the first of its kind at this scale at GMP, this paper highlights key practical considerations and learning opportunities for future tactical deployment for both police strategic and tactical leaders, as well as policing academics

Cardiovascular disease, associated risk factors, and risk of dementia: An umbrella review of meta-analyses

Introduction: Cardiovascular diseases (CVDs) have been associated with an increased risk of dementia; yet the evidence is mixed. This review critically appraises and synthesises current evidence exploring associations between dementia risk and CVD and their risk factors, including coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and arterial stiffness. Methods: MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews with meta-analyses investigating the association between at least one of the CVDs of interest and dementia risk. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews was used to assess methodological quality. Results: Twenty-five meta-analyses published between 2007 and 2021 were included. Studies largely consisted of cohorts from North America and Europe. Findings were variable, with coronary heart disease, heart failure, and atrial fibrillation consistently associated with increased risk for all-cause dementia, but results were inconsistent for Alzheimer’s disease. Hypertension was more frequently associated with dementia during mid-life compared to late life. Findings concerning cholesterol were complex, and while results were inconsistent for low-density lipoprotein cholesterol and total cholesterol, there appeared to be no associations between triglycerides and high-density lipoprotein cholesterol. All meta-analyses investigating hypercholesterolaemia showed significant increases in dementia risk. There was a paucity of research on the association between arterial stiffness and dementia risk. Conclusion: Targeted CVD dementia prevention strategies could reduce dementia prevalence. Future research should determine the underpinning mechanisms linking heart and brain health to determine the most effective strategies for dementia risk reduction in CVD populations.Jacob Brain, Leanne Greene, Eugene Y. H. Tang, Jennie Louise, Amy Salter, Sarah Beach, Deborah Turnbull, Mario Siervo, Blossom C. M. Stephan, and Phillip J. Tull

How to manage refractory intracranial hypertension?

Intracranial hypertension is one of the major causes of secondary injury in traumatic brain injury leading to a significant burden of morbidity and mortality. We here present a review of available therapies for the treatment of refractory intracranial hypertension that is defined as an intracranial hypertension that does not respond to the firstline therapies. Second-line therapies that are available for the treatment of refractory intracranial hypertension include mild induced hypothermia, inotropes, and vasopressors for the control of cerebral perfusion pressure, transient hyperventilation, barbiturates, and decompressive craniectomy. Apart from decompressive craniectomy, these therapies are supported by the last guidelines published by the Brain Trauma Foundation (BTF). However, the level of evidence supporting them is low to moderate. This is probably partly explained by the fact that traumatic brain injury is extremely heterogeneous and requires multimodal and individualised care, which makes randomised clinical trials difficult to set up. On-going studies like those conducted on induced hypothermia (EUROTHERM3235) and on decompressive craniectomy (RESCUEicp) may lead to new perspectives for the management of patients suffering from refractory intracranial hypertension