Menin Inhibition With Revumenib for -Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with -rearranged () acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) acute leukemia.

Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.

Targeting RARA overexpression with tamibarotene, a potent and selective RARα agonist, is a novel approach in AML.

A superenhancer at the retinoic acid receptor alpha (RARA) gene is associated with RARA mRNA overexpression in ∼30% of non-acute promyelocytic leukemia acute myeloid leukemia (AML) and in ∼50% of myelodysplastic syndromes (MDS). RARA overexpression is an actionable target for treatment with tamibarotene, an oral potent and selective RARα agonist. Sensitivity to the RARα agonist tamibarotene was demonstrated in RARA-high but not RARA-low preclinical AML models.

Elevated average maximum intrabolus pressure on high-resolution manometry is associated with esophageal dysmotility and delayed esophageal emptying on timed barium esophagram.

Background: Intrabolus pressure (IBP) recorded by high-resolution manometry (HRM) portrays the compartmentalized force on a bolus during esophageal peristalsis. HRM may be a reliable screening tool for esophageal dysmotility in patients with elevated average maximum IBP (AM-IBP). Timed barium esophagram (TBE) is a validated measure of esophageal emptying disorders, such as esophagogastric junction outflow obstruction and achalasia.

Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens.

Background And Aims: Most patients with small intestinal bacterial overgrowth (SIBO) produce hydrogen by fermentation of dietary carbohydrates; however, ∼30% of patients with SIBO are colonized with Archaea, anaerobic organisms that produce methane. SIBO is associated with a plethora of symptoms and conditions, but their diagnostic significance is unclear. We aimed to determine if specific symptoms and conditions are associated with methanogenic SIBO.

A qualitative study exploring personal recovery meaning and the potential influence of clinical recovery status on this meaning 20 years after a first-episode psychosis.

Purpose: Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.

Food Insecurity Is an Independent Risk Factor for Depressive Symptoms in Survivors of Digestive Cancers.

Background: Colorectal and other digestive cancer survivors are at increased risk of depression, which can negatively affect health outcomes. Food insecurity (FI), the lack of consistent access to enough food, can also contribute to these health complications. The objective of this study was to determine the relationship between FI and depressive symptoms within this population.

Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-Results of the phase 1 inhibitor cohort.

Background: Fitusiran, an investigational small interfering RNA therapy, reduces antithrombin production to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors.

Objectives: To evaluate the safety and efficacy of fitusiran treatment for people with moderate/severe hemophilia A or B with inhibitors.

Patients/methods: In this open-label phase 1, part D study, 17 males with hemophilia A or B with inhibitors received three once-monthly subcutaneous injections of fitusiran 50 mg (n = 6) or 80 mg (n = 11); followed for up to 112 days.

Antegrade Therapy for Management of Choledocholithiasis through Endoscopic Ultrasound-Guided Hepaticogastrostomy in a Patient with Surgically Altered Gastrointestinal Anatomy.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HG) is a technique used to access the biliary tree in patients with surgically altered anatomy. Additionally, development of EUS-HG fistula permits intraductal therapy, thereby preventing patients from requiring surgery or percutaneous transhepatic biliary drainage (PTBD), thus decreasing morbidity. This clinical vignette describes an 83-year-old man with a history of gangrenous cholecystitis requiring cholecystectomy, partial gastrectomy, and Roux-en-Y gastrojejunostomy who presented to an outside hospital with abdominal pain and fever and found to have cholangitis and choledocholithiasis.

Thrombin generation in plasma of patients with haemophilia A and B with inhibitors: Effects of bypassing agents and antithrombin reduction.

Antithrombin (AT) reduction has been shown to improve thrombin generation (TG) in haemophilia with or without inhibitors. As treatment with bypassing agents (BPAs) may be required in patients with breakthrough bleeding while receiving AT-lowering therapy, we assessed TG in platelet-poor plasma samples from haemophilia patients in the presence of BPA (recombinant activated factor VII [rFVIIa; 1.25 or 2.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

Objectives: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure.

Design: Prospective cohort study.

Setting: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital.

The iHOPE-20 study: mortality in first episode psychosis-a 20-year follow-up of the Dublin first episode cohort.

Purpose: Increased mortality rates have been found in those with a diagnosis of psychosis; studies suggest a shortened life expectancy of up to 20 years less than that of the general population. This study aimed to investigate the mortality of a first episode psychosis cohort at 20-year follow-up, compare it to that of the general Irish population, and explore whether the mortality gap has changed over time.

Methods: 171 individuals diagnosed with a first episode psychosis identified between 1995 and 1999 in a community mental health service were traced.

The iHOPE-20 study: Relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis.

Objective: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measure and compare outcomes reflecting modern clinical practice, mental health policy and research agendas. Our study aimed to address this gap.

Method: iHOPE-20 is a prospective 20-year follow-up study of a FEP incidence cohort ( = 171) conducted between 2014 and 2017 in Ireland.

A randomized study of a smartphone application compared with booklet to improve service user's knowledge of their legal rights.

Background: The Mental Health Act 2001 has introduced significant changes to the process of admission to hospital for individuals affected by mental health disorders. This study aimed to determine whether a newly designed smartphone application could result in an improvement in service users' knowledge of their rights compared with the paper booklet.

Methods: This was a randomized study conducted in an outpatient and day-hospital in North Dublin.

Service users' perspective of their admission: a report of study findings.

Objectives: The 'Service Users' Perspective of their Admission' study examined voluntarily and involuntarily admitted services users' perception of coercion during the admission process and whether this was associated with factors such as the therapeutic alliance, satisfaction with services, functioning and quality of life. This report aims to collate the findings of the study.

Methods: The study was undertaken across three community mental health services in Ireland.

'Recovery' in the Real World: Service User Experiences of Mental Health Service Use and Recommendations for Change 20 Years on from a First Episode Psychosis.

Little is known about how recovery oriented policy and legislative changes influence service users' perceptions of mental health care over time. Although the recovery approach is endorsed in many countries, qualitative research examining its impact on service use experiences has been lacking. This study aimed to explore this impact as well as experiences of service utilisation and suggestions for change with people diagnosed with a First Episode Psychosis between 1995 and 1999.

Clozapine Use in a Cohort of First-Episode Psychosis.

Purpose/background: For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducing psychotic symptoms.

Methods/procedures: Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 (N = 171).

Caregiver burden and distress following the patient's discharge from psychiatric hospital.

Caring for someone with a mental illness is increasingly occurring within the community. As a result, family members who fulfil a caregiving role may experience substantial levels of burden and psychological distress. This study investigates the level of burden and psychological distress reported by caregivers after the patient's admission.

Feasibility of a psychosis information intervention to improve mental health literacy for professional groups in contact with young people.

The aim of this study was to assess the feasibility of a psychosis information intervention for professionals in contact with young people in Ireland. A quasi-experimental pre- and post-intervention design was used. One thousand and thirty-two professionals received an information intervention designed to improve mental health literacy (MHL) and confidence in providing help to people with psychosis.

The prognostic value of formal thought disorder following first episode psychosis.

Background: Formal thought disorder (FTD) is associated with poor outcome in established psychotic illnesses and it can be assessed as a categorical or dimensional variable. However, its influence on functional outcome and hospitalisation patterns in early psychosis has not been investigated. We evaluated the relationship between FTD and these outcomes in a first episode psychosis (FEP) sample.

Neighbourhood characteristics and the incidence of first-episode psychosis and duration of untreated psychosis.

Background: The incidence of psychotic disorders varies between geographical areas and it has been hypothesized that neighbourhood-level factors may influence this variation. It is also plausible that the duration of untreated psychosis (DUP) is associated with neighbourhood characteristics. The aims of this study were to determine whether the incidence of first-episode psychosis (FEP) and the DUP are associated with the level of social deprivation, fragmentation, social capital and population density.