Pre-specification of statistical analysis approaches in published clinical trial protocols was inadequate

OBJECTIVES: Results from randomized trials can depend on the statistical analysis approach used. It is important to prespecify the analysis approach in the trial protocol to avoid selective reporting of analyses based on those which provide the most favourable results. We undertook a review of published trial protocols to assess how often the statistical analysis of the primary outcome was adequately prespecified. METHODS: We searched protocols of randomized trials indexed in PubMed in November 2016. We identified whether the following aspects of the statistical analysis approach for the primary outcome were adequately prespecified: (1) analysis population; (2) analysis model; (3) use of covariates; and (4) method of handling missing data. RESULTS: e identified 99 eligible protocols. Very few protocols adequately prespecified the analysis population (8/99, 8%), analysis model (27/99, 27%), covariates (40/99, 40%), or approach to handling missing data (10/99, 10%). Most protocols did not adequately predefine any of these four aspects of their statistical analysis approach (39%) or predefined only one aspect (36%). No protocols adequately predefined all four aspects of the analysis. CONCLUSION: The statistical analysis approach is rarely prespecified in published trial protocols. This may allow selective reporting of results based on different analyses

ETHICAL: Ethnic Disparities In COVID-19 Admissions in east London

This study aims to assess whether there is a difference in age and sex adjusted outcomes in different ethnicities of patients with confirmed COVID 19 admitted to Barts Health. The study will test the hypothesis that there is an association between health outcomes; in terms of need for ITU admission and mortality; and ethnicity in COVID-19 positive patients admitted to Barts Health; with patients of Black, Asian and other Minority Ethnicities having poorer outcomes as compared to patients of White ethnicity

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

PURPOSE: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. METHODS: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10–5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. CONCLUSIONS: We did not identify any survival benefit from critical care admission following surgery

Prevalence of diabetic retinopathy in Indigenous and non-Indigenous Australians: a systematic review and meta-analysis

TOPIC: This systematic review and meta-analysis summarises evidence relating to the prevalence of diabetic retinopathy (DR) among Indigenous and non-Indigenous Australians. CLINICAL RELEVANCE: Indigenous Australians suffer disproportionately from diabetes-related complications. Exploring ethnic variation in disease is important for equitable distribution of resources and may lead to identification of ethnic-specific modifiable risk factors. Existing DR prevalence studies comparing Indigenous and non-Indigenous Australians have shown conflicting results. METHODS: This study was conducted following Joanna Briggs Institute guidance on systematic reviews of prevalence studies (PROSPERO ID: CRD42022259048). We performed searches of Medline (Ovid), EMBASE, and Web of Science until October 2021, using a strategy designed by an information specialist. We included studies reporting DR prevalence among diabetic patients in Indigenous and non-Indigenous Australian populations. Two independent reviewers performed quality assessments using a 9-item appraisal tool. Meta-analysis and meta-regression were performed using double arcsine transformation and a random-effects model comparing Indigenous and non-Indigenous subgroups. RESULTS: Fifteen studies with 8219 participants met criteria for inclusion. The Indigenous subgroup scored lower on the appraisal tool compared to the non-Indigenous subgroup (mean score 50% vs 72%, p=0.04). In the unadjusted meta-analysis, DR prevalence in the Indigenous subgroup (30.2% [95%CI: 24.9-25.7]) did not differ significantly (p=0.17) from the non-Indigenous subgroup (23.7% (95%CI: 16.8-31.4]). After adjusting for age and for quality, DR prevalence was higher in the Indigenous subgroup (p-values<0.01), with prevalence ratio point estimates ranging between 1.72-2.58, depending on the meta-regression model. For the secondary outcomes, prevalence estimates were higher in the Indigenous subgroup for diabetic macular oedema (8.7% vs 2.7%, p=0.02) and vision-threatening DR (8.6% vs 3.0%, p=0.03), but not for proliferative DR (2.5% vs 0.8%, p=0.07). CONCLUSION: Indigenous studies scored lower for methodological quality, raising the possibility that systematic differences in research practices may be leading to underestimation of disease burden. After adjusting for age and for quality, we found a higher DR prevalence in the Indigenous subgroup. This contrasts with a previous review which reported the opposite finding of lower DR prevalence using unadjusted pooled estimates. Future epidemiological work exploring DR burden in Indigenous communities should aim to address methodological weaknesses identified by this review

CT methods for measuring glenoid bone loss are inaccurate, and not reproducible or interchangeable.

AIMS: Glenoid bone loss is a significant problem in the management of shoulder instability. The threshold at which the bone loss is considered "critical" requiring bony reconstruction has steadily dropped and is now approximately 15%. This necessitates accurate measurement in order that the correct operation is performed. CT scanning is the most commonly used modality and there are a number of techniques described to measure the bone loss however few have been validated. The aim of this study was to assess the accuracy of the most commonly used techniques for measuring glenoid bone loss on CT. METHODS: Anatomically accurate models with known glenoid diameter and degree of bone loss were used to determine the mathematical and statistical accuracy of six of the most commonly described techniques (relative diameter, linear ipsilateral circle of best fit (COBF), linear contralateral COBF, Pico, Sugaya, and circle line methods). The models were prepared at 13.8%, 17.6%, and 22.9% bone loss. Sequential CT scans were taken and randomized. Blinded reviewers made repeated measurements using the different techniques with a threshold for theoretical bone grafting set at 15%. RESULTS: At 13.8%, only the Pico technique measured under the threshold. At 17.6% and 22.9% bone loss all techniques measured above the threshold. The Pico technique was 97.1% accurate, but had a high false-negative rate and poor sensitivity underestimating the need for grafting. The Sugaya technique had 100% specificity but 25% of the measurements were incorrectly above the threshold. A contralateral COBF underestimates the area by 16% and the diameter by 5 to 7%. CONCLUSION: No one method stands out as being truly accurate and clinicians need to be aware of the limitations of their chosen technique. They are not interchangeable, and caution must be used when reading the literature as comparisons are not reliable

Plasma plume effects on the conductivity of amorphous-LaAlO₃/SrTiO₃ interfaces grown by pulsed laser deposition in O₂ and Ar

Amorphous LaAlO3/SrTiO3 interfaces exhibit metallic conductivity similarto those found for the extensively studied crystalline-LaAlO3/SrTiO3 interfaces. Here, we investigate the conductivity of the amorphous-LaAlO3/SrTiO3 interfaces grown in different pressures of O2 and Ar background gases. During the deposition, the LaAlO3 ablation plume is also studied, in situ, by fast photography and space-resolved optical emission spectroscopy. An interesting correlation between interfacial conductivity and kinetic energy of the Al atoms in the plume is observed: to assure conducting interfaces of amorphous-LaAlO3/SrTiO3, the kinetic energy of Al should be higher than 1 eV. Our findings add further insights on mechanisms leading to interfacial conductivity in SrTiO3-based oxide heterostructures

No association between ambient particulate matter exposure during pregnancy and stillbirth risk in the north of England, 1962–1992

Objectives: Research evidence suggests that exposure to ambient air pollutants can adversely affect the growth and development of the foetus and infant survival. Much less is known regarding the potential for an association between black smoke air pollution and stillbirth risk. This potential association was examined using data from the historical cohort UK Particulate Matter and Perinatal Events Research (PAMPER) study. Methods: Using data from paper-based neonatal records from the two major maternity hospitals in Newcastle upon Tyne (UK), a birth record database of all singletons born during 1961–1992 to mothers resident in the city was constructed. Weekly black smoke levels were obtained from routine data recorded at 20 air pollution monitoring stations over the study period. A two-stage statistical modelling strategy was used, incorporating temporally and spatially varying covariates to estimate black smoke exposure during each trimester and for the whole pregnancy period for each individual pregnancy. Conditional logistic regression models, with stratification on year of birth, were used to assess potential associations between black smoke exposures in pregnancy and stillbirth risk. Results: The PAMPER database consists of 90,537 births, between 1962 and 1992, with complete gestational age and residential address information, of which 812 were stillborn. There was no association between black smoke exposures in any trimester or across whole pregnancy and risk of stillbirth. Adjustment for potential confounders did not alter these results. Conclusions: While black smoke in pregnancy is likely to be related to other pregnancy outcomes, our findings do not suggest that black smoke air pollution exposure during pregnancy increases the risk of stillbirth

Biological nitrification inhibition by Brachiaria humidicola roots varies with soil type and inhibits nitrifying bacteria, but not other major soil microorganisms

The tropical pasture grass Brachiaria humidiola (Rendle) Schweick releases nitrification inhibitory compounds from its roots, a phenomenon termed 'biological nitrification inhibition' (BNI). We investigated the influence of root exudates of B. humidicola on nitrification, major soil microorganisms and plant growth promoting microorganisms using two contrasting soil types, Andosol and Cambisol. The addition of root exudates (containing BNI activity that is expressed in Allylthiourea unit (ATU)) was standardized in a bioassay against a synthetic inhibitor of nitrification, allylthiourea, and their function in soil was compared to inhibition caused by the synthetic nitrification inhibitor dicyandiamide. At 30 and 40 ATU g-1 soil, root exudates inhibited nitrification by 95% in fresh Cambisol after 60 days. Nitrification was also similarly inhibited in rhizosphere soils of Cambisol where B. humidicola was grown for 6 months. Root exudates did not inhibit other soil microorganisms, including gram-negative bacteria, total cultivable bacteria and fluorescent pseudomonads. Root exudates, when added to pure cultures of Nitrosomonas europaea, inhibited their growth, but did not inhibit the growth of several plant growth promoting microorganisms, Azospirillum lipoferum, Rhizobium leguminosarum and Azotobacter chroococcum. Our results indicate that the nitrification inhibitors released by B. humidicola roots inhibited nitrifying bacteria, but did not negatively affect other major soil microorganisms and the effectiveness of the inhibitory effect varied with soil type

Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

INTRODUCTION Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. METHODS Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria. RESULTS One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult. CONCLUSIONS An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven