On 11 June 2009, the World Health Organisation (WHO) raised the influenza pandemic alert to Level 6 (defined as ‘sustained community level outbreaks in at least one other country in another WHO ...region’) because of the emergence of a novel influenza A/H1N1 subtype. 1 Australia’s first laboratory confirmed case of pandemic (H1N1) 2009 virus, a NSW woman who had visited Los Angeles, was reported in the second week of May 2009. The National Institute for Occupational Safety and Health (NIOSH) regulates the testing and certification of respiratory protection equipment. 2 The NIOSH tests filters for the effects of loading (particle burden), temperature, and relative humidity and requires a minimum filtration efficiency of 95%, 99% or 99·97% using neutralized 0·075‐mm count median diameter solid aerosols at 85 l/min. Jefferson and colleagues concluded that more experimental studies were needed to identify the effectiveness of wearing face masks or respirators in reducing exhaled infectious viral particles. 7 In 2009, we reported the first prospective cluster‐randomized trial comparing surgical masks, non‐fit‐tested P2 masks (N95 equivalent) and no masks in prevention of influenza‐like illness (ILI) in households. 10 Intention to treat analysis showed no significant difference in the relative risk of ILI in the mask groups compared with the control group.
The “2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation” provides recommendations to guide clinicians in the treatment of patients with atrial ...fibrillation.
A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the “2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation” and the “2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation” have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.
Abstract Purpose The aim of this study was to compare the frequency and liability costs associated with radiology malpractice claims relative to other medical services and to evaluate the clinical ...context and case disposition associated with radiology malpractice claims. Methods This HIPAA-compliant study was exempted from institutional review board approval. The Comparative Benchmarking System database, a repository of more than 300,000 medical malpractice cases in the United States, was queried for closed claims over a five-year period (2008-2012). Claims were categorized by the medical service primarily responsible for the claim and the paid total loss. For all cases in which radiology was the primary responsible service, the case abstracts were evaluated to determine injury severity, claimant type by setting, claim allegation, process of care involved, case disposition, modality involved, and body section. Intracategory comparisons were made on the basis of the frequency of indemnity payment and total indemnity payment for paid cases, using χ2 and Wilcoxon rank-sum tests. Results Radiology was the eighth most likely responsible service to be implicated in a medical malpractice claim, with a median total paid loss (indemnity payment plus defense cost plus administrative expense) per closed case of $30,091 (mean, $205,619 ± $508,883). Radiology claims were most commonly associated with high- and medium-severity injuries (93.3% 820 of 879; 95% confidence interval CI, 91.7%-94.95%), the outpatient setting (66.3% 581 of 876; 95% CI, 63.0%-69.2%), and diagnosis-related allegations (ie, failure to diagnose or delayed diagnosis) (57.3% 504 of 879; 95% CI, 54.0%-60.6%). A high proportion of claims pertained to cancer diagnoses (44.0% 222 of 504; 95% CI, 39.7%-48.3%). A total of 62.3% (548 of 879; 95% CI, 59.1%-65.5%) of radiology claims were closed without indemnity payments; 37.7% (331 of 879; 95% CI, 34.5%-40.9%) were closed with a median indemnity payment of $175,000 (range, $112-$6,691,762; mean $481,094 ± $727,636). Conclusions Radiology malpractice claims most commonly involve diagnosis-related allegations in the outpatient setting, particularly cancer diagnoses, with approximately one-third of claims resulting in payouts to the claimants.
The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without ...albuminuria have not been well studied.
We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, ≥7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m
of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding.
Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval CI, 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo.
In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo but was associated with adverse events. (Funded by Sanofi and Lexicon Pharmaceuticals; SCORED ClinicalTrials.gov number, NCT03315143.).
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can ...adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibroblasts and macrophages causing collagen deposition, TGFβ production and induction of senescence in surrounding cholangiocytes and hepatocytes. Finally, we study how inhibition of TGFβ-signalling disrupts the transmission of senescence and restores liver function. We identify cellular senescence as a detrimental mechanism in the development of biliary injury. Our results identify TGFβ as a potential therapeutic target to limit senescence-dependent aggravation in human cholangiopathies.
We introduce MultiPiles, a visualization to explore time‐series of dense, weighted networks. MultiPiles is based on the physical analogy of piling adjacency matrices, each one representing a single ...temporal snapshot. Common interfaces for visualizing dynamic networks use techniques such as: flipping/animation; small multiples; or summary views in isolation. Our proposed ‘piling’ metaphor presents a hybrid of these techniques, leveraging each one's advantages, as well as offering the ability to scale to networks with hundreds of temporal snapshots. While the MultiPiles technique is applicable to many domains, our prototype was initially designed to help neuroscientists investigate changes in brain connectivity networks over several hundred snapshots. The piling metaphor and associated interaction and visual encodings allowed neuroscientists to explore their data, prior to a statistical analysis. They detected high‐level temporal patterns in individual networks and this helped them to formulate and reject several hypotheses.
During allogeneic hematopoietic cell transplantation (alloHCT), nonhematopoietic cell interleukin-33 (IL-33) is augmented and released by recipient conditioning to promote type 1 alloimmunity and ...lethal acute graft-versus-host disease (GVHD). Yet, IL-33 is highly pleiotropic and exhibits potent immunoregulatory properties in the absence of coincident proinflammatory stimuli. We tested whether peri-alloHCT IL-33 delivery can protect against development of GVHD by augmenting IL-33–associated regulatory mechanisms. IL-33 administration augmented the frequency of regulatory T cells (Tregs) expressing the IL-33 receptor, suppression of tumorigenicity-2 (ST2), which persist following total body irradiation. ST2 expression is not exclusive to Tregs and IL-33 expands innate immune cells with regulatory or reparative properties. However, selective depletion of recipient Foxp3+ cells concurrent with peri-alloHCT IL-33 administration accelerated acute GVHD lethality. IL-33–expanded Tregs protected recipients from GVHD by controlling macrophage activation and preventing accumulation of effector T cells in GVHD-target tissue. IL-33 stimulation of ST2 on Tregs activates p38 MAPK, which drives expansion of the ST2+ Treg subset. Associated mechanistic studies revealed that proliferating Tregs exhibit IL-33–independent upregulation of ST2 and the adoptive transfer of st2+ but not st2− Tregs mediated GVHD protection. In total, these data demonstrate the protective capacity of peri-alloHCT administration of IL-33 and IL-33–responsive Tregs in mouse models of acute GVHD. These findings provide strong support that the immunoregulatory relationship between IL-33 and Tregs can be harnessed therapeutically to prevent GVHD after alloHCT for treatment of malignancy or as a means for tolerance induction in solid organ transplantation.
•Peri-alloHCT IL-33 delivery prevents acute GVHD through MAPK-dependent expansion of radiation-resistant recipient ST2+ Tregs.•IL-33–expanded Tregs regulate myeloid cell differentiation and activation, and limit effector T-cell accumulation in GVHD-target tissue.
Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse ...transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1 notifications in the state over this period. Phylogenetic analysis was performed to identify subtype-specific transmission clusters. Subtype B and non-B infections differed across all demographics analysed (
< 0.001). We found a strong positive association for infections among females, individuals not born in Australia or reporting heterosexual transmission being of non-B origin. Further, we found an overall increase in non-B infections among men who have sex with men from 50 to 79% in the last 10 years. However, we also found differences between non-B subtypes; heterosexual transmission was positively associated with subtype C only. In addition, the majority of subtype B infections were associated with clusters, while the majority of non-B infections were singletons. However, we found seven non-B clusters (≥5 sequences) indicative of local ongoing transmission. In conclusion, we present how the HIV-1 epidemic has changed over time in NSW, becoming more heterogeneous with distinct subtype-specific demographic associations.
Marine species and ecosystems are widely affected by anthropogenic stressors, ranging from pollution and fishing to climate change. Comprehensive assessments of how species and ecosystems are ...impacted by anthropogenic stressors are critical for guiding conservation and management investments. Previous global risk or vulnerability assessments have focused on marine habitats, or on limited taxa or specific regions. However, information about the susceptibility of marine species across a range of taxa to different stressors everywhere is required to predict how marine biodiversity will respond to human pressures. We present a novel framework that uses life‐history traits to assess species' vulnerability to a stressor, which we compare across more than 44,000 species from 12 taxonomic groups (classes). Using expert elicitation and literature review, we assessed every combination of each of 42 traits and 22 anthropogenic stressors to calculate each species' or representative species group's sensitivity and adaptive capacity to stressors, and then used these assessments to derive their overall relative vulnerability. The stressors with the greatest potential impact were related to biomass removal (e.g., fisheries), pollution, and climate change. The taxa with the highest vulnerabilities across the range of stressors were mollusks, corals, and echinoderms, while elasmobranchs had the highest vulnerability to fishing‐related stressors. Traits likely to confer vulnerability to climate change stressors were related to the presence of calcium carbonate structures, and whether a species exists across the interface of marine, terrestrial, and atmospheric realms. Traits likely to confer vulnerability to pollution stressors were related to planktonic state, organism size, and respiration. Such a replicable, broadly applicable method is useful for informing ocean conservation and management decisions at a range of scales, and the framework is amenable to further testing and improvement. Our framework for assessing the vulnerability of marine species is the first critical step toward generating cumulative human impact maps based on comprehensive assessments of species, rather than habitats.
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