Native T1 mapping: inter-study, inter-observer and inter-center reproducibility in hemodialysis patients

Background Native T1 mapping is a cardiovascular magnetic resonance (CMR) technique that associates with markers of fibrosis and strain in hemodialysis patients. The reproducibility of T1 mapping in hemodialysis patients, prone to changes in fluid status, is unknown. Accurate quantification of myocardial fibrosis in this population has prognostic potential. Methods Using 3 Tesla CMR, we report the results of 1) the inter-study, inter-observer and intra-observer reproducibility of native T1 mapping in 10 hemodialysis patients; 2) inter-study reproducibility of left ventricular (LV) structure and function in 10 hemodialysis patients; 3) the agreement of native T1 map and native T1 phantom analyses between two centres in 20 hemodialysis patients; 4) the effect of changes in markers of fluid status on native T1 values in 10 hemodialysis patients. Results Inter-study, inter-observer and intra-observer variability of native T1 mapping were excellent with co-efficients of variation (CoV) of 0.7, 0.3 and 0.4% respectively. Inter-study CoV for LV structure and function were: LV mass = 1%; ejection fraction = 1.1%; LV end-diastolic volume = 5.2%; LV end-systolic volume = 5.6%. Inter-centre variability of analysis techniques were excellent with CoV for basal and mid-native T1 slices between 0.8–1.2%. Phantom analyses showed comparable native T1 times between centres, despite different scanners and acquisition sequences (centre 1: 1192.7 ± 7.5 ms, centre 2: 1205.5 ± 5 ms). For the 10 patients who underwent inter-study testing, change in body weight (Δweight) between scans correlated with change in LV end-diastolic volume (ΔLVEDV) (r = 0.682;P = 0.03) representing altered fluid status between scans. There were no correlations between change in native T1 between scans (ΔT1) and ΔLVEDV or Δweight (P > 0.6). Linear regression confirmed ΔT1 was unaffected by ΔLVEDV or Δweight (P > 0.59). Conclusions Myocardial native T1 is reproducible in HD patients and unaffected by changes in fluid status at the levels we observed. Native T1 mapping is a potential imaging biomarker for myocardial fibrosis in patients with end-stage renal disease

Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19–a data-driven retrospective cohort study

Objectives: To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths. Design: An EHR-based, retrospective cohort study. Setting: Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE). Participants: In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively. Main outcome measures: One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021. Results: From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31–4.38) and IR was 6.27% (95% CI, 6.26–6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. Conclusions: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions

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La prefazione colloca il testo nella fortuna critica che è andata maturandosi dagli anni Ottanta ad oggi sull'argomento a soggetto del volume, un laboratorio di sperimentazione video degli anni Settanta. Inoltre nella prefazione si rende conto della struttura proposta nel libro e nella sua suddivisione in due parti divise da un atlante di immagin

Association between Parkinson’s Disease and Cigarette Smoking, Rural Living, Well-Water Consumption, Farming and Pesticide Use: Systematic Review and Meta-Analysis

<div><p>Objective</p><p>Bradford Hill’s viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson’s disease (PD) and rural living, farming and pesticide use. The results were compared with an assessment based upon meta-analysis. For comparison, we also evaluated the association between PD and cigarette smoking as a “positive control” because a strong inverse association has been described consistently in the literature.</p><p>Methods</p><p>PubMed was searched systematically to identify all published epidemiological studies that evaluated associations between Parkinson’s disease (PD) and cigarette smoking, rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat. Studies were categorized into two study quality groups (Tier 1 or Tier 2); data were abstracted and a forest plot of relative risks (RRs) was developed for each risk factor. In addition, when available, RRs were tabulated for more highly exposed individuals compared with the unexposed. Summary RRs for each risk factor were calculated by meta-analysis of Tier 1, Tier 2 and all studies combined, with sensitivity analyses stratified by other study characteristics. Indices of between-study heterogeneity and evidence of reporting bias were assessed. Bradford Hill’s viewpoints were used to determine if a causal relationship between PD and each risk factor was supported by the weight of the evidence.</p><p>Findings</p><p>There was a consistent inverse (negative) association between current cigarette smoking and PD risk. In contrast, associations between PD and rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat were less consistent when assessed quantitatively or qualitatively.</p><p>Conclusion</p><p>The weight of the evidence and meta-analysis support the conclusion that there is a causal relationship between PD risk and cigarette smoking, or some unknown factor correlated with cigarette smoking. There may be risk factors associated with rural living, farming, pesticide use or well-water consumption that are causally related to PD, but the studies to date have not identified such factors. To overcome the limitations of research in this area, future studies will have to better characterize the onset of PD and its relationship to rural living, farming and exposure to pesticides.</p></div

Association between ever use (Panel a) or high use (Panel b) of paraquat and Parkinson’s disease.

<p>The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.g001" target="_blank">Fig 1</a> for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref018" target="_blank">18</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref055" target="_blank">55</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref057" target="_blank">57</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref059" target="_blank">59</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref068" target="_blank">68</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref069" target="_blank">69</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref081" target="_blank">81</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref092" target="_blank">92</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref114" target="_blank">114</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref132" target="_blank">132</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref135" target="_blank">135</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref154" target="_blank">154</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref156" target="_blank">156</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref160" target="_blank">160</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref165" target="_blank">165</a>].</p

Association between high herbicide (Panel a), high fungicide (Panel b) or high insecticide use (Panel c) and Parkinson’s disease.

<p>The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.g001" target="_blank">Fig 1</a> for instructions on how to interpret forest plots). RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref055" target="_blank">55</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref081" target="_blank">81</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref098" target="_blank">98</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref115" target="_blank">115</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref121" target="_blank">121</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref130" target="_blank">130</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref135" target="_blank">135</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref143" target="_blank">143</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref150" target="_blank">150</a>].</p

Heterogeneity estimates for each risk factor based on between-study variance (τ²) among Tier 1, Tier 2 or Tiers 1&2 studies combined.

<p>Heterogeneity estimates for each risk factor based on between-study variance (τ²) among Tier 1, Tier 2 or Tiers 1&2 studies combined.</p

Bradford Hill viewpoints.

<p>Bradford Hill viewpoints.</p

Association between rural living and Parkinson’s disease.

<p>The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.g001" target="_blank">Fig 1</a> for instructions on how to interpret forest plots). RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref054" target="_blank">54</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref056" target="_blank">56</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref058" target="_blank">58</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref059" target="_blank">59</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref064" target="_blank">64</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref076" target="_blank">76</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref098" target="_blank">98</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref100" target="_blank">100</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref102" target="_blank">102</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref104" target="_blank">104</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref114" target="_blank">114</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref130" target="_blank">130</a>].</p

Association between the heavy or long-term cigarette smoking and Parkinson’s disease.

<p>The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.g001" target="_blank">Fig 1</a> for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval, M & F = males and females, PD = Parkinson’s disease. Citations for studies appearing in this figure can be found here: [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref018" target="_blank">18</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref055" target="_blank">55</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref059" target="_blank">59</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref062" target="_blank">62</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref064" target="_blank">64</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref066" target="_blank">66</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref068" target="_blank">68</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref070" target="_blank">70</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref071" target="_blank">71</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref074" target="_blank">74</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref075" target="_blank">75</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref077" target="_blank">77</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref080" target="_blank">80</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref082" target="_blank">82</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref084" target="_blank">84</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref088" target="_blank">88</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref090" target="_blank">90</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref091" target="_blank">91</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref093" target="_blank">93</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref095" target="_blank">95</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151841#pone.0151841.ref111" target="_blank">111</a>].</p