Objective
To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE).
...Methods
We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model.
Results
Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC—mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (
n
= 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio OR 3.1 95%CI 2.1–14.5;
p
= 0.002). Mortality with severe (19.0%; OR 5.1 95%CI 1.4–17.9;
p
= 0.011), moderate (11.2%; OR 2.7 95%CI 1.1–6.8;
p
= 0.031), and mild CAC (12.6%; OR 3.1 95%CI 1.4–6.9;
p
= 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0–7.1;
p
= 0.050) and 2.6 (95%CI 0.9–7.1;
p
= 0.069) for the overall model. PE-related mortality was 4.0% (
n
= 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 95%CI 1.1–10.7;
p
= 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 95%CI 1.0–34.0;
p
= 0.049), with moderate CAC 6.7% (OR 4.0 95%CI 1.1–14.6;
p
= 0.033), and with mild 4.9% (OR 2.9 95%CI 0.8–9.9;
p
= 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9–20.7;
p =
0.074) and 3.4 (95%CI 0.7–17.4;
p
= 0.141) for the overall model. Patients with sub-massive PE showed similar results.
Conclusion
CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients.
Key Points
• Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism.
• Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism.
• Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.
We develop methods for estimating the size of hard-to-reach populations from data collected using network-based questions on standard surveys. Such data arise by asking respondents how many people ...they know in a specific group (e.g., people named Michael, intravenous drug users). The Network Scale up Method (NSUM) is a tool for producing population size estimates using these indirect measures of respondents' networks. Killworth et al. Soc. Netw. 20 (1998a) 23-50, Evaluation Review 22 (1998b) 289-308 proposed maximum likelihood estimators of population size for a fixed effects model in which respondents' degrees or personal network sizes are treated as fixed. We extend this by treating personal network sizes as random effects, yielding principled statements of uncertainty. This allows us to generalize the model to account for variation in people's propensity to know people in particular subgroups (barrier effects), such as their tendency to know people like themselves, as well as their lack of awareness of or reluctance to acknowledge their contacts' group memberships (transmission bias). NSUM estimates also suffer from recall bias, in which respondents tend to underestimate the number of members of larger groups that they know, and conversely for smaller groups. We propose a data-driven adjustment method to deal with this. Our methods perform well in simulation studies, generating improved estimates and calibrated uncertainty intervals, as well as in back estimates of real sample data. We apply them to data from a study of HIV/AIDS prevalence in Curitiba, Brazil. Our results show that when transmission bias is present, external information about its likely extent can greatly improve the estimates. The methods are implemented in the NSUM R package.
Calmodulin (CaM) is a highly conserved mediator of calcium (Ca2+)‐dependent signalling and modulates various cardiac ion channels. Genotyping has revealed several CaM mutations associated with long ...QT syndrome (LQTS). LQTS patients display prolonged ventricular recovery times (QT interval), increasing their risk of incurring life‐threatening arrhythmic events. Loss‐of‐function mutations to Kv7.1 (which drives the slow delayed rectifier potassium current, IKs, a key ventricular repolarising current) are the largest contributor to congenital LQTS (>50% of cases). CaM modulates Kv7.1 to produce a Ca2+‐sensitive IKs, but little is known about the consequences of LQTS‐associated CaM mutations on Kv7.1 function. Here, we present novel data characterising the biophysical and modulatory properties of three LQTS‐associated CaM variants (D95V, N97I and D131H). We showed that mutations induced structural alterations in CaM and reduced affinity for Kv7.1, when compared with wild‐type (WT). Using HEK293T cells expressing Kv7.1 channel subunits (KCNQ1/KCNE1) and patch‐clamp electrophysiology, we demonstrated that LQTS‐associated CaM variants reduced current density at systolic Ca2+ concentrations (1 μm), revealing a direct QT‐prolonging modulatory effect. Our data highlight for the first time that LQTS‐associated perturbations to CaM's structure impede complex formation with Kv7.1 and subsequently result in reduced IKs. This provides a novel mechanistic insight into how the perturbed structure–function relationship of CaM variants contributes to the LQTS phenotype.
Key points
Calmodulin (CaM) is a ubiquitous, highly conserved calcium (Ca2+) sensor playing a key role in cardiac muscle contraction.
Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS), a life‐threatening cardiac arrhythmia syndrome.
LQTS‐associated CaM variants (D95V, N97I and D131H) induced structural alterations, altered binding to Kv7.1 and reduced IKs.
Our data provide a novel mechanistic insight into how the perturbed structure–function relationship of CaM variants contributes to the LQTS phenotype.
figure legend LQTS‐CaM proteins displayed structural differences, with CaM variants undergoing less Ca2+‐induced conformational change when compared with CaM‐WT. These alternative conformations contribute to a reduced binding affinity of CaM to the C‐terminus of Kv7.1 (KCNQ1), more particularly in the presence of Ca2+. In cells, this translates to a reduction in IKs for LQTS‐associated CaM variants, and subsequently the prolongation of the ventricular action potential (QT interval). These findings highlight how the perturbed structure–function relationship of CaM variants and Kv7.1 contributes to the LQTS phenotype.
To assess the association between computed tomography pulmonary angiography (CTPA) atrial measurements and both 30-day pulmonary embolism (PE)-related adverse events and mortality, and non-PE-related ...mortality, and to identify the best predictors of these outcomes by comparing atrial measurements and widely used clinical and imaging variables.
Retrospective single-center pilot study. Acute PE patients diagnosed on CTPA who also had a transthoracic echocardiogram, electrocardiogram, and troponin T were included. CTPA left atrial (LA) and right atrial (RA) volume and short-axis diameter were measured and compared between outcome groups, along with right ventricular/left ventricular diameter ratio, interventricular septal bowing, tricuspid annular plane systolic excursion, electrocardiogram, and troponin T.
A total of 350 patients. LA volume and diameter were associated with PE-related adverse events (P≤0.01). LA volume was the only atrial measurement associated with PE-related mortality (P=0.03), with no atrial measurements associated with non-PE-related mortality. Troponin was most associated with PE-related adverse events and mortality (both area under the curve AUC=0.77). On multivariate analysis, combination models did not greatly improve PE-related adverse events prediction compared with troponin alone. For PE-related mortality, the best models were the combination of troponin, age, and either LA volume (AUC=0.86) or diameter (AUC=0.87).
Among patients with acute PE, CTPA LA volume is the only imaging parameter associated with PE-related mortality and is the best imaging predictor of this outcome. Reduced CTPA LA volume and diameter, along with increased RA/LA volume and diameter ratios, are significantly associated with 30-day PE-related adverse events, but not with non-PE-related mortality.
In their study, Clark et al.1 did not acknowledge 85 research papers produced by many different researchers (56 lead authors and more than 180 co-authors from more than 90 institutions) that have ...reported significant effects of elevated levels of CO2 on the behaviour of fish from coral reefs and other habitats, including at least 8 papers that were written by the authors of Clark et al.1 (Supplementary Table 1). ...Clark et al.1 did not use the same life stages and ecological histories of the fish species used in previous studies. ...the only species that Clark et al.1 collected in light traps had not previously been tested for CO2 sensitivity, and variation between different species in behavioural sensitivity to ocean acidification is already well known2,11. Increased temperature is known to diminish or reverse the effects of elevated CO2 on risk-assessment behaviour14, and A. polyacanthus is one of the most thermally sensitive coral reef fish species, which could explain the absence of significant effects for this species in 2016, whereas they observed significant effects in 2014.
Objective
To determine patient experience and perception following a diagnosis of non‐muscle‐invasive bladder cancer (NMIBC).
Patient and methods
Patients were part of a prospective multicentre ...observational study recruiting patients with NMIBC for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mixed‐methods approach comprising: (i) the Brief Illness Perception Questionnaire (Brief‐IPQ) and (ii) semi‐structured interviews to explore patients’ experience of having haematuria, and initial and subsequent experience with a NMIBC diagnosis. Both assessments were completed at 6 months after NMIBC diagnosis.
Results
A total of 213 patients completed the Brief‐IPQ. Patients felt that they had minimal symptoms (median interquartile range, IQR score 2 0–5) and were not particularly affected emotionally (median IQR score 3 1–6) with a minimal effect to their daily life (median IQR score 2 0–5). However, they remained concerned about their cancer diagnosis (median IQR score 5 3–8) and felt that they had no personal control over the cancer (median IQR score 2 2–5) and believed that their illness would affect them for some time (median IQR score 6 3–10). A significant association with a lower personal control of the disease (P < 0.05) and a poorer understanding of the management of NMIBC (P < 0.05) was seen in patients aged >70 years. Many patients were uncertain about the cause of bladder cancer. Qualitative analysis found that at initial presentation of haematuria, most patients were not aware of the risk of bladder cancer. Patients were most anxious and psychologically affected between the interval of cystoscopy diagnosis and transurethral resection of bladder tumour (TURBT). Following TURBT, most patients were positive about their cancer prognosis.
Conclusion
Patients with NMIBC have a poor perception of disease control and believe that their disease will continue over a prolonged period of time. This is particularly more pertinent in the elderly. Patients are most psychologically affected during the interval between cancer diagnosis following cystoscopy and TURBT. Health awareness about bladder cancer remained poor with a significant number of patients unaware of the causes of bladder cancer. Psychological support and prompt TURBT following bladder cancer diagnosis would help improve the mental health of patients with NMIBC.
Background. Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 ...Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs. Methods. Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities. Results. Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case. Conclusions. Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources.
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