Acid-suppression medications and bacterial gastroenteritis:a population-based cohort study

AIMS: To investigate whether acid suppression medicines (ASMs) increase the risk of bacterial gastroenteritis. METHODS: A population-based, propensity-score matched cohort study using a record-linkage database in Tayside, Scotland. The study consisted of 188,323 exposed to ASMs [proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RA)] and 376,646 controls (a propensity-score matched cohort from the rest of population who were not exposed to ASMs) between 1999 and 2013. The main outcome measure was a positive stool test for C. difficile, Campylobacter, Salmonella, Shigella or Escherichia coli O157. The association between ASMs and risk of bacterial gastroenteritis was assessed by a Cox regression model. RESULTS: There were 22,705 positive test results (15,273 Clostridium difficile (toxin positive), 6,590 Campylobacter, 852 Salmonella, 129 Shigella and 193 Escherichia coli O157, not mutually exclusive) with a total of 5,729,743 person-years follow up time in Tayside, 1999-2013. The adjusted hazard ratios (HRs) for culture positive diarrhoea for the PPIs and H2RA exposed vs unexposed cohort were 2.72 [95% confidence interval (CI) 2.33, 3.17] during follow up time for samples submitted from the community and 1.28 (95% CI 1.08, 1.52) for samples submitted from hospitals. Compared with the unexposed cohort, patients in the exposed group had increased risks of C. difficile and Campylobacter [adjusted HRs of 1.70 (95% CI 1.28, 2.25), 3.71 (95% CI 3.04, 4.53) for community samples, and 1.42 (95% CI 1.17, 1.71), 4.53 (95% CI 1.75, 11.8) for hospital samples, respectively]. CONCLUSIONS: The results suggest that community prescribed ASMs were associated with increased rates of C. difficile and Campylobacter positive gastroenteritis in both the community and hospital settings

Factors associated with timeliness of post-primary care referral, diagnosis and treatment for lung cancer: population-based, data-linkage study

BACKGROUND: The NHS Cancer Plan for England set waiting time targets for cancer referral (14 days from GP referral to first hospital appointment) and treatment (31 days from diagnosis, 62 days from urgent GP referral). Interim diagnostic intervals can also be calculated. The factors that influence timely post-primary care referral, diagnosis and treatment for lung cancer are not known. METHODS: Northern and Yorkshire Cancer Registry, Hospital Episode Statistics and lung cancer audit data sets were linked. Logistic regression was used to investigate the factors (socioeconomic position, age, sex, histology, co-morbidity, year of diagnosis, stage and performance status (PS)) that may influence the likelihood of referral, diagnosis and treatment within target, for 28 733 lung cancer patients diagnosed in 2006–2010. RESULTS: Late-stage, poor PS and small-cell histology were associated with a higher likelihood of post-primary care referral, diagnosis and treatment within target. Older patients were significantly less likely to receive treatment within the 31-day (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.69–0.91) and 62-day target (OR=0.80, 95% CI 0.67–0.95) compared with younger patients. CONCLUSIONS: Older patients waited longer for treatment and this may be unjustified. Patients who appeared ill were referred, diagnosed and treated more quickly and this ‘sicker quicker’ effect may cancel out system socioeconomic inequalities that might result in longer time intervals for more deprived patients

The relation between socioeconomic and demographic factors and tumour stage in women diagnosed with breast cancer in Denmark, 1983–1999

The authors investigated the association between socioeconomic position and stage of breast cancer at the time of diagnosis in a nationwide Danish study. All 28 765 women with a primary invasive breast cancer diagnosed between 1983 and 1999 were identified in a nationwide clinical database and information on socioeconomic variables was obtained from Statistics Denmark. The risk of being diagnosed with a high-risk breast cancer, that is size >20 mm, lymph-node positive, ductal histology/high histologic grade and hormone receptor negative, was analysed by multivariate logistic regression. The adjusted odds ratio (OR) for high-risk breast cancer was reduced with longer education with a 12% reduced risk (95% confidence interval (CI), 0.80,0.96) in women with higher education and increased with reduced disposable income (low income group: OR, 1.22; 95% CI, 1.10,1.34). There was an urban–rural gradient, with higher risk among rural women (OR 1.10; 95 % CI, 1.02, 1.18) and lower risk among women in the capital suburbs (OR, 0.85; 95% CI, 0.78, 0.93) and capital area (OR, 0.93; 95% CI, 0.84–1.02). These factors were significant only for postmenopausal women, although similar patterns were observed among the premenopausal women, suggesting a subgroup of aggressive premenopausal breast cancers less influenced by socioeconomic factors

Seaview Survey Photo-quadrat and Image Classification Dataset

The primary scientific dataset arising from the XL Catlin Seaview Survey project is the “Seaview Survey Photo-quadrat and Image Classification Dataset”, consisting of: (1) over one million standardised, downward-facing “photo-quadrat” images covering approximately 1m2 of the sea floor; (2) human-classified annotations that can be used to train and validate image classifiers;\ua0(3) benthic cover data arising from the application of machine learning classifiers to the photo-quadrats; and\ua0(4)\ua0the triplets of raw images (covering 360o) from which the photo-quadrats were derived.Photo-quadrats were collected between 2012 and 2018 at 860 transect locations around the world, including: the Caribbean and Bermuda, the Indian Ocean (Maldives, Chagos Archipelago), the Coral Triangle (Indonesia, Philippines, Timor-Leste, Solomon Islands), the Great Barrier Reef, Taiwan and Hawaii.For additional information regarding methodology, data structure, organization and size, please see attached document “Dataset documentation”

Evasion of IFN-γ Signaling by Francisella novicida Is Dependent upon Francisella Outer Membrane Protein C

Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. An outer membrane protein (FTT0918) of F. tularensis subsp. tularensis has been identified as a virulence factor. We generated a F. novicida (F. tularensis subsp. novicida) FTN_0444 (homolog of FTT0918) fopC mutant to study the virulence-associated mechanism(s) of FTT0918.The ΔfopC strain phenotype was characterized using immunological and biochemical assays. Attenuated virulence via the pulmonary route in wildtype C57BL/6 and BALB/c mice, as well as in knockout (KO) mice, including MHC I, MHC II, and µmT (B cell deficient), but not in IFN-γ or IFN-γR KO mice was observed. Primary bone marrow derived macrophages (BMDM) prepared from C57BL/6 mice treated with rIFN-γ exhibited greater inhibition of intracellular ΔfopC than wildtype U112 strain replication; whereas, IFN-γR KO macrophages showed no IFN-γ-dependent inhibition of ΔfopC replication. Moreover, phosphorylation of STAT1 was downregulated by the wildtype strain, but not the fopC mutant, in rIFN-γ treated macrophages. Addition of NG-monomethyl-L-arginine, an NOS inhibitor, led to an increase of ΔfopC replication to that seen in the BMDM unstimulated with rIFN-γ. Enzymatic screening of ΔfopC revealed aberrant acid phosphatase activity and localization. Furthermore, a greater abundance of different proteins in the culture supernatants of ΔfopC than that in the wildtype U112 strain was observed.F. novicida FopC protein facilitates evasion of IFN-γ-mediated immune defense(s) by down-regulation of STAT1 phosphorylation and nitric oxide production, thereby promoting virulence. Additionally, the FopC protein also may play a role in maintaining outer membrane stability (integrity) facilitating the activity and localization of acid phosphatases and other F. novicida cell components

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2)

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.</p