Targeted sequencing of candidate gene regions for myelofibrosis in dogs.

BACKGROUND: Myelofibrosis often lacks an identifiable cause in dogs. In humans, most primary myelofibrosis cases develop secondary to driver mutations in JAK2, CALR, or MPL. OBJECTIVES: To determine the prevalence of variants in JAK2, CALR, or MPL candidate regions in dogs with myelofibrosis and in healthy dogs. ANIMALS: Twenty-six dogs with myelofibrosis that underwent bone marrow biopsy between 2010 and 2018 and 25 control dogs matched for age, sex, and breed. METHODS: Cross-sectional study. Amplicon sequencing of JAK2 exons 12 and 14, CALR exon 9, and MPL exon 10 was performed on formalin-fixed, decalcified, paraffin-embedded bone marrow (myelofibrosis) or peripheral blood (control) DNA. Somatic variants were categorized as likely-benign or possibly-pathogenic based on predicted impact on protein function. Within the myelofibrosis group, hematologic variables and survival were compared by variant status (none, likely-benign only, and ≥1 possibly-pathogenic). The effect of age on variant count was analyzed using linear regression. RESULTS: Eighteen of 26 (69%) myelofibrosis cases had somatic variants, including 9 classified as possibly-pathogenic. No somatic variants were detected in controls. Within the myelofibrosis group, hematologic variables and survival did not differ by variant status. The number of somatic variants per myelofibrosis case increased with age (estimate, 0.69; SE, 0.29; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Somatic variants might initiate or perpetuate myelofibrosis in dogs. Our findings suggest the occurrence of clonal hematopoiesis in dogs, with increasing incidence with age, as observed in humans.

Emerging models and trends in mental health crisis care in England: a national investigation of crisis care systems.

BACKGROUND: Inpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day units; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature. We therefore aimed to describe the types and distribution of crisis care models across England through a national survey. METHODS: We carried out comprehensive mapping of crisis resolution teams (CRTs) using previous surveys, websites and multiple official data sources. Managers of CRTs were invited to participate as key informants who were familiar with the provision and organisation of crisis care services within their catchment area. The survey could be completed online or via telephone interview with a researcher, and elicited details about types of crisis care delivered in the local catchment area. RESULTS: We mapped a total of 200 adult CRTs and completed the survey with 184 (92%). Of the 200 mapped adult CRTs, there was a local (i.e., within the adult CRT catchment area) children and young persons CRT for 84 (42%), and an older adults CRT for 73 (37%). While all but one health region in England provided CRTs for working age adults, there was high variability regarding provision of all other community crisis service models and system configurations. Crisis cafes, street triage teams and separate crisis assessment services have all proliferated since a similar survey in 2016, while provision of acute day units has reduced. CONCLUSIONS: The composition of catchment area crisis systems varies greatly across England and popularity of models seems unrelated to strength of evidence. A group of emerging crisis care models with varying functions within service systems are increasingly prevalent: they have potential to offer greater choice and flexibility in managing crises, but an evidence base regarding impact on service user experiences and outcomes is yet to be established.

Evaluating the accuracy of the XVI dual registration tool compared with manual soft tissue matching to localise tumour volumes for post-prostatectomy patients receiving radiotherapy.

INTRODUCTION: Cone beam computerised tomography (CBCT) enables soft tissue visualisation to optimise matching in the post-prostatectomy setting, but is associated with inter-observer variability. This study assessed the accuracy and consistency of automated soft tissue localisation using XVI's dual registration tool (DRT). METHODS: Sixty CBCT images from ten post-prostatectomy patients were matched using: (i) the DRT and (ii) manual soft tissue registration by six radiation therapists (RTs). Shifts in the three Cartesian planes were recorded. The accuracy of the match was determined by comparing shifts to matches performed by two genitourinary radiation oncologists (ROs). A Bland-Altman method was used to assess the 95% levels of agreement (LoA). A clinical threshold of 3 mm was used to define equivalence between methods of matching. RESULTS: The 95% LoA between DRT-ROs in the superior/inferior, left/right and anterior/posterior directions were -2.21 to +3.18 mm, -0.77 to +0.84 mm, and -1.52 to +4.12 mm, respectively. The 95% LoA between RTs-ROs in the superior/inferior, left/right and anterior/posterior directions were -1.89 to +1.86 mm, -0.71 to +0.62 mm and -2.8 to +3.43 mm, respectively. Five DRT CBCT matches (8.33%) were outside the 3-mm threshold, all in the setting of bladder underfilling or rectal gas. The mean time for manual matching was 82 versus 65 s for DRT. CONCLUSIONS: XVI's DRT is comparable with RTs manually matching soft tissue on CBCT. The DRT can minimise RT inter-observer variability; however, involuntary bladder and rectal filling can influence the tools accuracy, highlighting the need for RT evaluation of the DRT match.