Publications by authors named "Andrew Perkins"

Background: The therapeutic alliance is an important predictor of treatment outcomes but people who use alcohol and other drugs report mixed views of treatment providers. We analysed patients' accounts of inpatient detoxification staff to ascertain whether, and if so how, relationships with them, and thus the therapeutic alliance, might be improved.

Methods: Semi-structured qualitative interviews were conducted (in 2022/2023) with 20 people (14 males; 6 females) who had just completed inpatient detoxification in sixteen different facilities.

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Purpose: Anemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor-naive and -experienced patients.

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Neural tube closure in vertebrates is achieved through a highly dynamic and coordinated series of morphogenic events involving neuroepithelium, surface ectoderm, and neural plate border. Failure of this process in the caudal region causes spina bifida. Grainyhead-like 3 (GRHL3) is an indispensable transcription factor for neural tube closure as constitutive inactivation of the gene in mice leads to fully penetrant spina bifida.

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The SP/KLF family of transcription factors harbour three C-terminal C2H2 zinc fingers interspersed by two linkers which confers DNA-binding to a 9-10 bp motif. Mutations in KLF1, the founding member of the family, are common. Missense mutations in linker two result in a mild phenotype.

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Key Clinical Message: This case suggests using dual orexin receptor antagonists to treat alcohol use disorder and comorbid sleep disorders may be effective, commencing treatment in withdrawal and continuing it to prevent relapse.

Abstract: Effective medications for the treatment of alcohol use disorder are limited. This is partially due to the heterogenous nature of the symptomatology associated with alcohol use disorder and the abundance of presenting comorbidities.

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Article Synopsis
  • Bone marrow fibrosis (BMF) is linked to myelofibrosis and can affect prognosis, but this study explores its relationship with treatment outcomes in patients receiving JAK inhibitors momelotinib and ruxolitinib.
  • In a study of patients with BMF, only momelotinib showed increased transfusion independence and hemoglobin levels, while ruxolitinib showed a decrease in hemoglobin.
  • The findings suggest that changes in BMF do not correlate with clinical improvements or survival benefits, indicating that BMF may not be an effective surrogate marker for assessing the efficacy of JAK inhibitors.
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Article Synopsis
  • - Patients with myelofibrosis suffer from various symptoms due to bone marrow fibrosis and inflammation, and improving these symptoms can enhance their quality of life.
  • - This study analyzed data from two phase III trials of momelotinib (SIMPLIFY-1 and SIMPLIFY-2) to determine a meaningful change threshold (MCT) for symptoms, finding it to be 8 points for treatment-naive patients and 6 points for those previously treated.
  • - Results showed that momelotinib effectively improved patient symptoms, suggesting that the traditional 50% reduction standard used in clinical trials may be too conservative and that momelotinib offers significant benefits compared to other treatments in myelofibrosis patients.
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Background: There is limited provision of inpatient detoxification relative to other treatments for alcohol and other drug (AOD) use. This means people often need to wait prior to detoxifying. However, waiting for healthcare is generally perceived as negative and stressful.

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The Philadelphia-negative myeloproliferative neoplasms (MPN) are a heterogeneous group of overlapping bone marrow disorders defined by characteristic peripheral blood counts and bone marrow morphological findings in conjunction with recurrent somatic mutations. The accurate diagnosis and subclassification of MPN relies upon careful reporting of bone marrow morphology combined with ancillary information in an integrated pathology report. This co-operative trial group study ALLG MPN01 (ANZCTR:12613000138785), led by the Australasian Leukaemia & Lymphoma Group (ALLG), aimed to describe the current approach to diagnosis of MPN in routine practice.

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Article Synopsis
  • Myelofibrosis (MF) is a chronic condition causing severe symptoms, particularly fatigue and anemia, which greatly affect patients' quality of life.
  • The JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib has shown promising results in clinical trials, significantly improving both anemia and overall MF-related symptoms compared to danazol.
  • The phase 3 MOMENTUM trial confirmed these benefits, with patients on momelotinib experiencing faster and lasting symptom relief, particularly in fatigue and physical functioning, as demonstrated by various patient-reported outcome measures.
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NSW Health is implementing genomics as a mainstream component of clinical care. The strategic, holistic approach is considering infrastructure, data governance and management, workforce, education, service planning and delivery. This work is generating insights about how to realise the promise of genomics in healthcare, highlighting the need for strong foundations, real-world application, accessibility and a focus on people using genomic information in clinical care.

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This case describes a young man with an unusual cause of severe osteoporosis and markedly deranged bone microarchitecture resulting in multiple fractures. A potentially pathogenic germline variant in the runt-related transcription factor 1 (RUNX1) gene was discovered by a focused 51-gene myeloid malignancy panel during investigation for his unexplained normochromic normocytic anemia. Further bone-specific genetic testing and a pedigree analysis were declined by the patient.

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Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g.

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Article Synopsis
  • - Congenital fibrinogen disorders (CFDs) vary greatly in how they show up clinically and the genetic causes behind them, making them complex to study.
  • - The relationship between a person's specific genetic makeup (genotype) and how the disorder presents itself (phenotype) is still not well understood.
  • - Future research will focus on improving genetic sequencing technology to better understand these disorders and enhance diagnosis and treatment options for patients.
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Article Synopsis
  • - The MOMENTUM study successfully showed that momelotinib, compared to danazol, provided significant improvements in symptoms, spleen size, and anemia in myelofibrosis patients at the 24-week mark, and this analysis focuses on outcomes from 24 to 48 weeks.
  • - The study involved 107 international sites with adult patients who had a history of myelofibrosis and were treated with a Janus kinase inhibitor, with participants randomly assigned to receive either momelotinib or danazol for 24 weeks.
  • - After 24 weeks, all patients transitioned to open-label momelotinib, and this updated analysis reports on the duration of responses and additional patient results through week 48
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Article Synopsis
  • Myelofibrosis (MF) causes significant health-related quality of life issues, and traditional clinical trials often use a basic measure of symptom improvement, which may not capture the full range of patient experiences.
  • This study used advanced statistical methods to analyze how symptoms change over a 24-week period in patients with MF treated with momelotinib, comparing these changes to a control group.
  • Results showed that both momelotinib and ruxolitinib improved overall symptoms, but momelotinib consistently led to better outcomes, with more patients reporting improvements or stability compared to the control group.
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Article Synopsis
  • Momelotinib, a new treatment for myelofibrosis, shows promise by improving symptoms, spleen size, and anemia, unlike existing JAK inhibitors that primarily address symptoms and spleen enlargement.
  • The MOMENTUM study is a global phase 3 trial comparing momelotinib to danazol in patients with symptomatic myelofibrosis who have previously been treated with JAK inhibitors.
  • Results indicated that a higher percentage of patients treated with momelotinib experienced a significant reduction in their myelofibrosis-related symptoms compared to those on danazol.
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Vertical transmission of Renibacterium salmoninarum has been well-documented in anadromous salmonids but not in hatchery-reared inland trout. We assessed whether the bacterium is vertically transmitted in cutthroat trout (Oncorhynchus clarkii) from a Colorado, USA hatchery, and assessed the rate of transmission from male and female brood fish. Adult brood fish were killed, tested for R.

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A meeting of veterinary school faculty and partners, many associated with shelter medicine and/or community medicine programming, was convened at the 2019 Shelter Medicine Veterinary Educators Conference in Pullman, WA, to discuss challenges with shelter medicine program sustainability and defining the future. The discussion was facilitated by an outside consultant and is summarized in this manuscript. The goal of the meeting was to identify challenges and issues concerning the needs and goals for shelter medicine curricula to have long-term success in academic training.

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Patients with myelofibrosis (MF) who discontinue ruxolitinib due to progression/resistance have poor prognoses. JAK inhibitors control symptoms and reduce spleen volumes with limited impact on underlying disease pathophysiology. Murine double minute 2 (MDM2), a negative regulator of p53, is overexpressed in circulating malignant CD34 MF cells.

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Neural tube closure is a dynamic morphogenic event in early embryonic development. Perturbations of this process through either environmental or genetic factors induce the severe congenital malformations known collectively as neural tube defects (NTDs). Deficiencies in maternal folate intake have long been associated with NTDs, as have mutations in critical neurulation genes that include the Grainyhead-like 3 (Grhl3) gene.

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Stably silenced genes that display a high level of CpG dinucleotide methylation are refractory to the current generation of dCas9-based activation systems. To counter this, we create an improved activation system by coupling the catalytic domain of DNA demethylating enzyme TET1 with transcriptional activators (TETact). We show that TETact demethylation-coupled activation is able to induce transcription of suppressed genes, both individually and simultaneously in cells, and has utility across a number of cell types.

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