ABSTRACT
Border disease (BD) was first reported in 1959 in lambs from the border region of England and Wales. The causative virus (BD virus; BDV) has since been identified in several other ruminant species and pigs. The virus is prevalent in sheep flocks of UK, Europe and USA and has potential to inflict substantial economic losses. Natural BDV infection of pigs was first reported in the UK in 1992 from pigs with haemorrhagic lesions and more recently from healthy pigs in Spain and Japan. Here, a persistent problem of poor growth and anaemia in a small proportion of growing pigs on a mixed pig and sheep holding was investigated and tissues were tested in a pan viral microarray. The microarray detected BDV RNA in several tissues which was further confirmed by sequencing, specific BDV PCR and immunohistochemistry. Phylogenetically, the virus clustered with other BDVs in the sub-genotype 1b. This investigation highlights likely interspecies transmission of pestiviruses and their impact on pestivirus detection and eradication programs.
Subject(s)
Border Disease , Border disease virus , Pestivirus , Sheep Diseases , Swine Diseases , Animals , Border Disease/epidemiology , Border disease virus/genetics , Disease Outbreaks/veterinary , Genotype , Pestivirus/genetics , Sheep , Sheep Diseases/epidemiology , Swine , Swine Diseases/epidemiologyABSTRACT
PURPOSE: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. EXPERIMENTAL DESIGN: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. RESULTS: We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. CONCLUSIONS: For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Bridged Bicyclo Compounds, Heterocyclic , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Phosphatidylinositol 3-Kinases , Protein Kinase Inhibitors/adverse effects , Pyrazoles , Pyrimidines , SulfonamidesSubject(s)
Food Contamination/analysis , Lead Poisoning/veterinary , Refuse Disposal/methods , Wood , Animals , Animals, Domestic , Cattle , Cattle Diseases/epidemiology , Cattle Diseases/etiology , Chickens , Lead Poisoning/epidemiology , Lead Poisoning/etiology , Poultry Diseases/epidemiology , Poultry Diseases/etiology , United Kingdom/epidemiologyABSTRACT
OBJECTIVE: The primary purpose of this study was to use an ecological assessment model to obtain a better understanding of difficult situations that home visitors confront when implementing home visitation services. METHOD: A mixed method study was used which included conducting focus groups to identify specific situations faced by home visitors who implement the Healthy Families America model of child abuse and neglect prevention. The results of the focus groups were used to design a survey. The survey had 91 Healthy Families home visitors rate situations according to frequency and difficulty. RESULTS: The results revealed that situations that were ranked most difficult included working with families where there are limited resources, where family mental illness is present (e.g., threatening suicide), where there is substance use in the home, and where families are unmotivated. A factor analysis of the situations produced five factors that reflect the difficulty of doing home visitation: having a lack of clinical skill, addressing family difficulties, addressing parenting difficulties, resolving personal difficulties, and having a lack of experience. CONCLUSION: The situations identified in this study can assist in developing the competencies needed by home visitors. The factor analysis results can be conceptualized into an inventory for staff supervision, with workers completing the inventory to identify individual areas of training needs.
