Serotype-specific correlates of protection for pneumococcal carriage: an analysis of immunity in 19 countries.

Background: Pneumococcal conjugate vaccines (PCVs) provide direct protection against disease in those vaccinated, and interrupt transmission through the prevention of nasopharyngeal carriage. Methods: We analysed immunogenicity data from 5224 infants who received PCV in prime-boost schedules. We defined any increase in antibody between the one-month post-priming visit and the booster dose as an indication of nasopharyngeal carriage ('seroincidence'). We calculated antibody concentrations using receiver-operator characteristic curves, and used generalised additive models to compute their protective efficacy against seroincidence. To support seroincidence as a marker of carriage, we compared seroincidence in a randomised immunogenicity trial in Nepal with the serotype-specific prevalence of carriage in the same community. Findings: In Nepalese infants, seroincidence of carriage closely correlated with serotype-specific carriage prevalence in the community. In the larger data set, antibody concentrations associated with seroincidence were lowest for serotypes 6B and 23F (0.50 µg/mL and 0.63 µg/mL respectively), and highest for serotypes 19F and 14 (2.54 µg/mL and 2.48 µg/mL respectively). The protective efficacy of antibody at these levels was 62% and 74% for serotypes 6B and 23F, and 87% and 84% for serotypes 19F and 14. Protective correlates were on average 2.15 times higher in low/lower middle income countries than in high/upper middle income countries (GMR 2.15, 95%CI 1.46-3.17, p=0.0024). Interpretation: Antibody concentrations associated with protection vary between serotypes. Higher antibody concentrations are required for protection in low-income countries. These findings are important for global vaccination policy, to interrupt transmission by protecting against carriage

Frequencies and patterns of microbiology test requests from primary care in Oxfordshire, UK, 2008-2018: a retrospective cohort study of electronic health records to inform point of care testing

Objectives: To inform point-of-care test (POCT) development, we quantified the primary care demand for laboratory microbiology tests by describing their frequencies overall, frequencies of positives, most common organisms identified, temporal trends in testing and patterns of cotesting on the same and subsequent dates. Design: Retrospective cohort study. Setting: Primary care practices in Oxfordshire. Participants :393 905 patients (65% female; 49% aged 18–49). Primary and secondary outcome measures The frequencies of all microbiology tests requested between 2008 and 2018 were quantified. Patterns of cotesting were investigated with heat maps. All analyses were done overall, by sex and age categories. Results: 1 596 752 microbiology tests were requested. Urine culture±microscopy was the most common of all tests (n=673 612, 42%), was mainly requested without other tests and was the most common test requested in follow-up within 7 and 14 days. Of all urine cultures, 180 047 (27%) were positive and 172 651 (26%) showed mixed growth, and Escherichia coli was the most prevalent organism (132 277, 73% of positive urine cultures). Antenatal urine cultures and blood tests in pregnancy (hepatitis B, HIV and syphilis) formed a common test combination, consistent with their use in antenatal screening. Conclusions: The greatest burden of microbiology testing in primary care is attributable to urine culture ± microscopy; genital and routine antenatal urine and blood testing are also significant contributors. Further research should focus on the feasibility and impact of POCTs for these specimen types

Post-imaging colorectal cancer or interval cancer rates after computed tomographic colonography: A systematic review and meta-analysis

Background: CT colonography (CTC) is highly sensitive for colorectal cancer, but “interval” or postimaging colorectal cancer (PICRC) rates (diagnosis of cancer after initial negative CTC) are unknown, as are their underlying causes. Methods: We conducted a systematic review and meta-analysis of post-CTC PICRC rates and causes by searching MEDLINE, EMBASE and the Cochrane Register. We included randomised, cohort, cross-sectional or case-control studies published Jan 1994-Feb 2017, using CTC performed according to international consensus standards with aim of detecting cancer or polyps, and reporting PICRC rates or sufficient data to allow their calculation. Two independent reviewers extracted data from the study reports. We used random-effects meta-analysis to estimate pooled PICRC rates, expressed using (a) total number of cancers and (b) total number of CTC scans as denominators, and (c) per 1000 person-years. Primary study authors provided details of retrospective CTC image review and causes for each PICRC. The study is registered (PROSPERO:CRD42016046838). Findings: 2977 articles were screened and 12 analysed. These reported 19,867 patients (18-96 years; of 11,590 with sex data available, 6532 (56·4%) female) from March 2002-May 2015. At mean 34 months’ follow-up (range: 3 to 128·4 months), CTC detected 643 cancers and 29 PICRCs were diagnosed. The pooled PICRC rate was 4·42 PICRCs/100 cancers detected; 95%CI 3·03-6·42, corresponding to 1·61 PICRCs/1000 CTCs (95%CI 1·11-2·33) or 0·64 PICRCs/1000 person-years (95%CI 0·44-0·92). Heterogeneity was low (I2 =0%). Over half (17/28, 61%) of PICRCs were due to perceptual error and visible in retrospect. Interpretation: The 3-year PICRC rate post-CTC is 4·4%, or 0·64 per 1000 person-years, towards the lower end of range reported for colonoscopy. Most arise from perceptual errors. Radiologist training and quality assurance may help reduce PICRC rates. Funding: St Mark’s Hospital Foundation and the UCL/UCLH Biomedical Research Centre

Longer-term use of electronic cigarettes when provided as a stop smoking aid: Systematic review with meta-analyses.

Moderate certainty evidence supports use of nicotine electronic cigarettes to quit smoking combustible cigarettes. However, there is less certainty regarding how long people continue to use e-cigarettes after smoking cessation attempts. We set out to synthesise data on the proportion of people still using e-cigarettes or other study products at 6 months or longer in studies of e-cigarettes for smoking cessation. We updated Cochrane searches (November 2021). For the first time, we meta-analysed prevalence of continued e-cigarette use among individuals allocated to e-cigarette conditions, and among those individuals who had successfully quit smoking. We updated meta-analyses comparing proportions continuing product use among individuals allocated to use nicotine e-cigarettes and other treatments. We included 19 studies (n = 7787). The pooled prevalence of continued e-cigarette use at 6 months or longer was 54% (95% CI: 46% to 61%, I2 86%, N = 1482) in participants assigned to e-cigarette conditions. Of participants who had quit combustible cigarettes overall 70% were still using e-cigarettes at six months or longer (95% CI: 53% to 82%, I2 73%, N = 215). Heterogeneity in direction of effect precluded meta-analysis comparing long-term use of nicotine e-cigarettes with NRT. More people were using nicotine e-cigarettes at longest follow-up compared to non-nicotine e-cigarettes, but CIs included no difference (risk ratio 1.15, 95% CI: 0.94 to 1.41, n = 601). The levels of continued e-cigarette use observed may reflect the success of e-cigarettes as a quitting tool. Further research is needed to establish drivers of variation in and implications of continued use of e-cigarettes

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.Background and purpose: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. Methods: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. Results: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) −0.45), learning and memory (SMD −0.55), complex attention (SMD −0.54) and language (SMD −0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD −0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. Conclusions: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment

Inter-rater reliability of categorical versus continuous scoring of fish vitality: does it affect the utility of the reflex action mortality predictor (RAMP) approach?

Scoring reflex responsiveness and injury of aquatic organisms has gained popularity as predictors of discard survival. Given this method relies upon the individual interpretation of scoring criteria, an evaluation of its robustness is done here to test whether protocol-instructed, multiple raters with diverse backgrounds (research scientist, technician, and student) are able to produce similar or the same reflex and injury score for one of the same flatfish (European plaice, Pleuronectes platessa) after experiencing commercial fishing stressors. Inter-rater reliability for three raters was assessed by using a 3-point categorical scale (‘absent’, ‘weak’, ‘strong’) and a tagged visual analogue continuous scale (tVAS, a 10 cm bar split in three labelled sections: 0 for ‘absent’, ‘weak’, ‘moderate’, and ‘strong’) for six reflex responses, and a 4-point scale for four injury types. Plaice (n = 304) were sampled from 17 research beam-trawl deployments during four trips. Fleiss kappa (categorical scores) and intra-class correlation coefficients (ICC, continuous scores) indicated variable inter-rater agreement by reflex type (ranging between 0.55 and 0.88, and 67% and 91% for Fleiss kappa and ICC, respectively), with least agreement among raters on extent of injury (Fleiss kappa between 0.08 and 0.27). Despite differences among raters, which did not significantly influence the relationship between impairment and predicted survival, combining categorical reflex and injury scores always produced a close relationship of such vitality indices and observed delayed mortality. The use of the continuous scale did not improve fit of these models compared with using the reflex impairment index based on categorical scores. Given these findings, we recommend using a 3-point categorical over a continuous scale. We also determined that training rather than experience of raters minimised inter-rater differences. Our results suggest that cost-efficient reflex impairment and injury scoring may be considered a robust technique to evaluate lethal stress and damage of this flatfish species on-board commercial beam-trawl vessels

Residential traffic exposure and pregnancy-related outcomes: a prospective birth cohort study

Background. The effects of ambient air pollution on pregnancy outcomes are under debate. Previous studies have used different air pollution exposure assessment methods. The considerable traffic-related intra-urban spatial variation needs to be considered in exposure assessment. Residential proximity to traffic is a proxy for traffic-related exposures that takes into account within-city contrasts. Methods. We investigated the association between residential proximity to traffic and various birth and pregnancy outcomes in 7,339 pregnant women and their children participating in a population-based cohort study. Residential proximity to traffic was defined as 1) distance-weighted traffic density in a 150 meter radius, and 2) proximity to a major road. We estimated associations of these exposures with birth weight, and with the risks of preterm birth and small size for gestational age at birth. Additionally, we examined associations with pregnancy-induced hypertension, (pre)eclampsia, and gestational diabetes. Results. There was considerable variation in distance-weighted traffic density. Almost fifteen percent of the participants lived within 50 m of a major road. Residential proximity to traffic was not associated with birth and pregnancy outcomes in the main analysis and in various sensitivity analyses. Conclusions. Mothers exposed to residential traffic had no higher risk of adverse birth outcomes or pregnancy complications in this study. Future studies may be refined by taking both temporal and spatial variation in air pollution exposure into account

The matching distribution

Tom Fanshawe introduces the probability distribution that forms the basis of elementary card games and tests of extra-sensory perceptio

An empirical investigation into the role of subjective prior probability in searching for potentially missing items

There are many examples from the scientific literature of visual search tasks in which the length, scope and success rate of the search have been shown to vary according to the searcher's expectations of whether the search target is likely to be present. This phenomenon has major practical implications, for instance in cancer screening, when the prevalence of the condition is low and the consequences of a missed disease diagnosis are severe. We consider this problem from an empirical Bayesian perspective to explain how the effect of a low prior probability, subjectively assessed by the searcher, might impact on the extent of the search. We show how the searcher's posterior probability that the target is present depends on the prior probability and the proportion of possible target locations already searched, and also consider the implications of imperfect search, when the probability of false-positive and false-negative decisions is non-zero. The theoretical results are applied to two studies of radiologists' visual assessment of pulmonary lesions on chest radiographs. Further application areas in diagnostic medicine and airport security are also discussed