153 research outputs found
Spatializing sociocultural research : a reading of mediation and meaning as third spaces
Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England
: Background: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. Methods: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. Results: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. Conclusions: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes
The fifth adaptor protein complex.
Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia
Performance of point-of-care HbA1c test devices: implications for use in clinical practice – a systematic review and meta-analysis
Regular monitoring of glycated hemoglobin subfraction A1c (HbA1c) in people with diabetes and treatment with glucose-lowering medications to improve glycaemic control can reduce the risk of developing complications [1]. In 2011, a World Health Organization consultation concluded that HbA1cat a threshold of 6.5% (48 mmol/mol) can be used as a diagnostic test for diabetes [2]. HbA1c monitoring often requires the patient to attend the health center twice: once to have blood taken and then returning to get test results and receive adjustments to medication. Point-of-care (POC) analysers are bench-top instruments that use a finger-prick blood sample and are designed for use in a treatment room or at the bed-side. They provide a test result within a few minutes allowing clinical decisions and medication changes to take place immediately. The suitability of many of these devices for the accurate measurement of HbA1c has been questioned, with some POC HbA1c test devices reported not to meet accepted accuracy and precision criteria [3]. Ideal imprecision goals for HbA1c should be coefficient of variation (CV) of <2% for HbA1c reported in % units (or <3% in SI units, mmol/mol) [4], [5], [6]. Most evaluations of POC HbA1c devices have taken place in laboratory settings [7], [8]; fewer studies have assessed device performance in a POC setting or with clinicians performing the tests [9], [10]. The only published review that has attempted to combine data from accuracy studies identified five studies covering three devices and compared correlation coefficients [11]. Systematically reporting and pooling data estimates of bias and precision between POC HbA1c devices and laboratory measurements would enable end users to assess which analysers best meet their analytical performance needs. This may be of particular importance for clinicians in primary care settings where much of the management of diabetes patients takes place. The comparison of accuracy between devices over the entire therapeutic range would need to be carried out by combining data on measurement error (bias) between POC and laboratory tests [12]. The aim of this study was to compare accuracy and precision of POC HbA1c devices with the local laboratory method based on data from published studies and discuss the clinical implications of the findings
Impact of patient and public involvement on enrolment and retention in clinical trials: Systematic review and meta-analysis
© Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Objective To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. Design Systematic review and meta-analysis. Data sources Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. Eligibility criteria Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). Data extraction and analysis Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. Results 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). Conclusions These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. Systematic review registration PROSPERO CRD42016043808
Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population
BACKGROUND
The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care.
CONTENT
MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values.
SUMMARY
Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR
Multivariate proteomic profiling identifies novel accessory proteins of coated vesicles.
Despite recent advances in mass spectrometry, proteomic characterization of transport vesicles remains challenging. Here, we describe a multivariate proteomics approach to analyzing clathrin-coated vesicles (CCVs) from HeLa cells. siRNA knockdown of coat components and different fractionation protocols were used to obtain modified coated vesicle-enriched fractions, which were compared by stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative mass spectrometry. 10 datasets were combined through principal component analysis into a "profiling" cluster analysis. Overall, 136 CCV-associated proteins were predicted, including 36 new proteins. The method identified >93% of established CCV coat proteins and assigned >91% correctly to intracellular or endocytic CCVs. Furthermore, the profiling analysis extends to less well characterized types of coated vesicles, and we identify and characterize the first AP-4 accessory protein, which we have named tepsin. Finally, our data explain how sequestration of TACC3 in cytosolic clathrin cages causes the severe mitotic defects observed in auxilin-depleted cells. The profiling approach can be adapted to address related cell and systems biological questions
Change in glomerular filtration rate over time in the Oxford Renal Cohort Study:observational study
Background: Decline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age. Aim: To determine the proportion of participants with a decline in estimated glomerular filtration rate (eGFR), identify determinants of decline, and determine proportions with chronic kidney disease (CKD) remission. Design and setting: Observational cohort study in UK primary care. Method: Data were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73 m2/year, improvement as eGFR increase >5 ml/min/1.73 m2/year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline. Results: There was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement, and 82 of 394 (21%) meeting CKD stage 1-4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure, and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function. Conclusion: This study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care.</p
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