Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the ...development of strategies to address this common disease.
The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months.
The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma.
This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.
This comprehensive meta-analysis was conducted to answer the question as to which procedure, pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) is more beneficial to malignant ...pleural mesothelioma patients' outcome.
Original research studies that evaluated long-term outcomes of P/D versus EPP were identified, from January 1990 to January 2014. The combined percent perioperative and 2-year mortality, and median survival were calculated according to both a fixed and a random effect model. The Q statistics and I(2) statistic were used to test for heterogeneity between the studies.
There were 24 distinct data sets, for a total of 1,512 patients treated with P/D, and 1,391 treated with EPP. There was a significantly higher proportion of short-term deaths in the EPP group versus the P/D group (percent mortality meta estimate; 4.5% vs 1.7%; p < 0.05). There was no statistically significant difference in 2-year mortality between the 2 groups, but there was significant heterogeneity.
The reanalysis of the large number of studies comparing P/D to EPP suggests that P/D is associated with a 2 ½-fold lower short-term mortality (perioperatively and within 30 days) than EPP. Pleurectomy decortication should therefore be preferred when technically feasible.
Morbidity from undiagnosed atrial fibrillation (AF) may be preventable with early detection. Many consumer wearables contain optical photoplethysmography (PPG) sensors to measure pulse rate. ...PPG-based software algorithms that detect irregular heart rhythms may identify undiagnosed AF in large populations using wearables, but minimizing false-positive detections is essential.
We performed a prospective remote clinical trial to examine a novel PPG-based algorithm for detecting undiagnosed AF from a range of wrist-worn devices. Adults aged ≥22 years in the United States without AF, using compatible wearable Fitbit devices and Android or iOS smartphones, were included. PPG data were analyzed using a novel algorithm that examines overlapping 5-minute pulse windows (tachograms). Eligible participants with an irregular heart rhythm detection (IHRD), defined as 11 consecutive irregular tachograms, were invited to schedule a telehealth visit and were mailed a 1-week ambulatory ECG patch monitor. The primary outcome was the positive predictive value of the first IHRD during ECG patch monitoring for concurrent AF.
A total of 455 699 participants enrolled (median age 47 years, 71% female, 73% White) between May 6 and October 1, 2020. IHRDs occurred for 4728 (1%) participants, and 2070 (4%) participants aged ≥65 years during a median of 122 (interquartile range, 110-134) days at risk for an IHRD. Among 1057 participants with an IHRD notification and subsequent analyzable ECG patch monitor, AF was present in 340 (32.2%). Of the 225 participants with another IHRD during ECG patch monitoring, 221 had concurrent AF on the ECG and 4 did not, resulting in an IHRD positive predictive value of 98.2% (95% CI, 95.5%-99.5%). For participants aged ≥65 years, the IHRD positive predictive value was 97.0% (95% CI, 91.4%-99.4%).
A novel PPG software algorithm for wearable Fitbit devices exhibited a high positive predictive value for concurrent AF and identified participants likely to have AF on subsequent ECG patch monitoring. Wearable devices may facilitate identifying individuals with undiagnosed AF.
URL: https://www.
gov; Unique identifier: NCT04380415.
Cognition and personality: an analysis of an emerging field Griffin, Andrea S.; Guillette, Lauren M.; Healy, Susan D.
Trends in ecology & evolution (Amsterdam),
April 2015, 2015-Apr, 2015-04-00, 20150401, Letnik:
30, Številka:
4
Journal Article
Recenzirano
•We question whether variation in personality relates to variation in cognition.•We propose ways to establish whether cognitive abilities are consistent.•We suggest possible shapes of a relationship ...between personality and cognition.•We point to two key challenges in addressing personality–cognition relationships.
It is now well established that individuals can differ consistently in their average levels of behaviour across different contexts. There have recently been calls to apply the same adaptive framework to interindividual differences in cognition. These calls have culminated in the suggestion that variation in personality and cognition should correlate. We suggest that both these appealing notions are conceptually and logistically problematic. We identify the first crucial step for establishing any cognition–personality relationship. This is to determine the degree to which cognitive abilities yield consistent task performance. We then suggest how to establish whether such consistency exists. Finally, we discuss why formulating predictions about how cognition might be related to personality is much more difficult than is currently realised.
Artificial intelligence (AI)-enabled analysis of 12-lead ECGs may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful ...and generalizable improvement in predictive accuracy beyond clinical risk factors for AF.
We trained a convolutional neural network (ECG-AI) to infer 5-year incident AF risk using 12-lead ECGs in patients receiving longitudinal primary care at Massachusetts General Hospital (MGH). We then fit 3 Cox proportional hazards models, composed of ECG-AI 5-year AF probability, CHARGE-AF clinical risk score (Cohorts for Heart and Aging in Genomic Epidemiology-Atrial Fibrillation), and terms for both ECG-AI and CHARGE-AF (CH-AI), respectively. We assessed model performance by calculating discrimination (area under the receiver operating characteristic curve) and calibration in an internal test set and 2 external test sets (Brigham and Women's Hospital BWH and UK Biobank). Models were recalibrated to estimate 2-year AF risk in the UK Biobank given limited available follow-up. We used saliency mapping to identify ECG features most influential on ECG-AI risk predictions and assessed correlation between ECG-AI and CHARGE-AF linear predictors.
The training set comprised 45 770 individuals (age 55±17 years, 53% women, 2171 AF events) and the test sets comprised 83 162 individuals (age 59±13 years, 56% women, 2424 AF events). Area under the receiver operating characteristic curve was comparable using CHARGE-AF (MGH, 0.802 95% CI, 0.767-0.836; BWH, 0.752 95% CI, 0.741-0.763; UK Biobank, 0.732 95% CI, 0.704-0.759) and ECG-AI (MGH, 0.823 95% CI, 0.790-0.856; BWH, 0.747 95% CI, 0.736-0.759; UK Biobank, 0.705 95% CI, 0.673-0.737). Area under the receiver operating characteristic curve was highest using CH-AI (MGH, 0.838 95% CI, 0.807 to 0.869; BWH, 0.777 95% CI, 0.766 to 0.788; UK Biobank, 0.746 95% CI, 0.716 to 0.776). Calibration error was low using ECG-AI (MGH, 0.0212; BWH, 0.0129; UK Biobank, 0.0035) and CH-AI (MGH, 0.012; BWH, 0.0108; UK Biobank, 0.0001). In saliency analyses, the ECG P-wave had the greatest influence on AI model predictions. ECG-AI and CHARGE-AF linear predictors were correlated (Pearson
: MGH, 0.61; BWH, 0.66; UK Biobank, 0.41).
AI-based analysis of 12-lead ECGs has similar predictive usefulness to a clinical risk factor model for incident AF and the approaches are complementary. ECG-AI may enable efficient quantification of future AF risk.
: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of ...expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.
: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.
: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations:
) a strong recommendation for the use of long-acting β
-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance;
) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year;
) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year;
) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy;
) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and
) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.
: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.
Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract is the principal determinant of lethality following allogeneic bone marrow transplantation (BMT). Here, we examined the mechanisms ...that initiate GVHD, including the relevant antigen-presenting cells. MHC class II was expressed on intestinal epithelial cells (IECs) within the ileum at steady state but was absent from the IECs of germ-free mice. IEC-specific deletion of MHC class II prevented the initiation of lethal GVHD in the GI tract. MHC class II expression on IECs was absent from mice deficient in the TLR adaptors MyD88 and TRIF and required IFNγ secretion by lamina propria lymphocytes. IFNγ responses are characteristically driven by IL-12 secretion from myeloid cells. Antibiotic-mediated depletion of the microbiota inhibited IL-12/23p40 production by ileal macrophages. IL-12/23p40 neutralization prevented MHC class II upregulation on IECs and initiation of lethal GVHD in the GI tract. Thus, MHC class II expression by IECs in the ileum initiates lethal GVHD, and blockade of IL-12/23p40 may represent a readily translatable therapeutic strategy.
Display omitted
•The microbiota influences MHC class II expression on IECs in the ileum•MHC class II expression on IECs requires an IL-12-IFNγ cytokine axis•MHC class II+ IECs present antigen, activate CD4+ T cells, and initiate lethal gut GVHD•IL-12/23p40 neutralization pretransplant prevents the initiation of lethal GVHD
Graft-versus-host disease in the gastrointestinal tract is the principal determinant of lethality following allogeneic bone marrow transplantation. Koyama et al. find that MHC class II-dependent antigen presentation by ileal intestinal epithelial cells (IECs) is critical for the initiation of lethal GVHD in the gut, define the requirements for IEC MHC class II expression, and propose IL-12 neutralization as a therapeutic strategy for GVHD.
Display omitted
Early detection of atrial fibrillation or flutter (AF) may enable prevention of downstream morbidity. Consumer wrist-worn wearable technology is capable of detecting AF by identifying ...irregular pulse waveforms using photoplethysmography (PPG). The validity of PPG-based software algorithms for AF detection requires prospective assessment.
The Fitbit Heart Study (NCT04380415) is a single-arm remote clinical trial examining the validity of a novel PPG-based software algorithm for detecting AF. The proprietary Fitbit algorithm examines pulse waveform intervals during analyzable periods in which participants are sufficiently stationary. Fitbit consumers with compatible wrist-worn trackers or smartwatches were invited to participate. Enrollment began May 6, 2020 and as of October 1, 2020, 455,699 participants enrolled. Participants in whom an irregular heart rhythm was detected were invited to attend a telehealth visit and eligible participants were then mailed a one-week single lead electrocardiographic (ECG) patch monitor. The primary study objective is to assess the positive predictive value of an irregular heart rhythm detection for AF during the ECG patch monitor period. Additional objectives will examine the validity of irregular pulse tachograms during subsequent heart rhythm detections, self-reported AF diagnoses and treatments, and relations between irregular heart rhythm detections and AF episode duration and time spent in AF.
The Fitbit Heart Study is a large-scale remote clinical trial comprising a unique software algorithm for detection of AF. The study results will provide critical insights into the use of consumer wearable technology for AF detection, and for characterizing the nature of AF episodes detected using consumer-based PPG technology.
Modified vaccinia virus Ankara (MVA) is the leading poxvirus vector for development of vaccines against diverse infectious diseases. This distinction is based on high expression of proteins and good ...immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety. Nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s). The search for host-range factors is exacerbated by the large number of deletions, truncations and mutations that occurred during the long passage history of MVA in chicken embryo fibroblasts. By whole genome sequencing of a panel of recombinant host-range extended (HRE) MVAs generated by marker rescue with 40 kbp segments of vaccinia virus DNA, we identified serine protease inhibitor 1 (SPI-1) as one of several candidate host-range factors present in those viruses that gained the ability to replicate in human cells. Electron microscopy revealed that the interruption of morphogenesis in human cells infected with MVA occurred at a similar stage as that of a vaccinia virus strain WR SPI-1 deletion mutant. Moreover, the introduction of the SPI-1 gene into the MVA genome led to more than a 2-log enhancement of virus spread in human diploid MRC-5 cells, whereas deletion of the gene diminished the spread of HRE viruses by similar extents. Furthermore, MRC-5 cells stably expressing SPI-1 also enhanced replication of MVA. A role for additional host range genes was suggested by the restoration of MVA replication to a lower level relative to HRE viruses, particularly in other human cell lines. Although multiple sequence alignments revealed genetic changes in addition to SPI-1 common to the HRE MVAs, no evidence for their host-range function was found by analysis thus far. Our finding that SPI-1 is host range factor for MVA should simplify use of high throughput RNAi or CRISPR/Cas single gene methods to identify additional viral and human restriction elements.
PDF
