Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for ALS.

Background: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to mutations.

Methods: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to mutations.

A qualitative exploration of cardiovascular disease patients' views and experiences with an eHealth cardiac rehabilitation intervention: The PATHway Project.

The aim of this study is to explore participants' views and experiences of an eHealth phase 3 cardiac rehabilitation (CR) intervention: Physical Activity Towards Health (PATHway). Sixty participants took part in the PATHway intervention. Debriefs were conducted after the six-month intervention.

Measuring quality of life in ALS/MND: validation of the WHOQOL-BREF.

The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model.

A Cross-sectional Study of Hospital Performance on ICU Utilization Practices for Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Intensive care unit (ICU) resources are a costly but effective commodity used in the management of critically ill patients with chronic obstructive pulmonary disease (COPD). ICU admission decisions are determined by patient diagnosis and severity of illness, but also may be affected by hospital differences in quality and performance. We investigate the variability in ICU utilization for patients with COPD and its association with hospital characteristics.

Hypersensitivity of bladder low threshold, wide dynamic range, afferent fibres following treatment with the chemotherapeutic drugs cyclophosphamide and ifosfamide.

The cytotoxic drugs cyclophosphamide (CPO) and ifosfamide (IFO) cause toxic urological effects due to the production of urinary metabolites that cause bladder inflammation. This study aimed to identify changes in the bladder afferent system following treatment with these drugs that might explain reported urological adverse effects. Intravesical pressure and afferent nerve activity were recorded during bladder distension and drug administration in isolated bladders from mice, 24 h after intraperitoneal treatment with cyclophosphamide (100 mg/kg), ifosphamide (200 mg/kg) or saline (control).

A Pilot retrospective analysis of alpha-blockers on recurrence in men with localised prostate cancer treated with radiotherapy.

While alpha-blockers are commonly used to reduce lower urinary tract symptoms in prostate cancer patients receiving radiotherapy, their impact on response to radiotherapy remains unknown. Therefore, this pilot study aimed to retrospectively determine if alpha-blockers use, influenced response to radiotherapy for localised prostate cancer. In total, 303 prostate cancer patients were included, consisting of 84 control (alpha-blocker naïve), 72 tamsulosin and 147 prazosin patients.

Disruption of hepatic one-carbon metabolism impairs mitochondrial function and enhances macrophage activity in methionine-choline-deficient mice.

One-carbon metabolism is a collection of metabolic cycles that supports methylation and provides one-carbon bound folates for the de novo synthesis of purine and thymidine nucleotides. The methylation of phosphatidylethanolamine to form choline has been extensively studied in the context of fatty liver disease. However, the role of one-carbon metabolism in supporting nucleotide synthesis during liver damage has not been addressed.

Updates on Selected Emerging Infectious Diseases of Ornamental Fish.

Emerging infectious diseases of ornamental fish are discussed with special focus on clinical relevance, detection, and treatment, where applicable. Important emerging infectious diseases of fish include goldfish herpesvirus, koi herpesvirus, carp edema virus, Erysipelothrix, Edwardsiella ictaluri, Edwardseilla piscicida, and Francisella. Some diseases are more species or genus specific, but many emerging diseases do not seem to have a species preference and affect a variety of species worldwide.

Inflammatory State After Intrathoracic Breast Implant Placement for Postpneumonectomy Syndrome.

We describe a case of a 16-year-old patient who underwent right pneumonectomy for pulmonary vein atresia and developed postpneumonectomy syndrome. She had an 800-cm saline-filled silicone tissue expander placed in the right hemithorax with resolution of her postpneumonectomy syndrome. However, 2 years later, she developed fevers, night sweats, and arthralgias.

Voiding Behavior and Efferent Bladder Function Altered in Mice Following Social Defeat but Not Witness Trauma.

Psychological stress is associated with bladder dysfunction, however, the local bladder mechanisms affected are not well understood. This study aimed to determine how psychological stress, caused by social defeat or witness trauma, affects voiding behavior and bladder function. Pairs of male C57Bl/6J mice were placed in a custom-made plexiglass chamber with an aggressor ARC(S) mouse for 1 h/day for 10 days.

The Association between Chronic Conditions, End-of-Life Health Care Use, and Documentation of Advance Care Planning among Patients with Cancer.

Multiple chronic conditions (MCCs) are associated with increased intensity of end-of-life (EOL) care, but their effect is not well explored in patients with cancer. We examined EOL health care intensity and advance care planning (ACP) documentation to better understand the association between MCCs and these outcomes. Retrospective cohort study.

Needs of Transitionally Housed Young People to Promote Occupational Participation.

This qualitative descriptive study explored what young people who are transitionally housed need to promote occupational participation. Nine young people and four staff members from a transitional living facility participated in interviews and focus groups. Results suggested that the young people need opportunities to practice independent living skills, develop routines to support employment, housing, and education, and receive more individualized support from service providers.

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis.

Objective: In amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology.

Methods: Longitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months).

Feasibility, Acceptability, and Clinical Effectiveness of a Technology-Enabled Cardiac Rehabilitation Platform (Physical Activity Toward Health-I): Randomized Controlled Trial.

Background: Cardiac rehabilitation (CR) is highly effective as secondary prevention for cardiovascular diseases (CVDs). Uptake of CR remains suboptimal (30% of eligible patients), and long-term adherence to a physically active lifestyle is even lower. Innovative strategies are needed to counteract this phenomenon.

The COX-2 inhibitor NS398 selectively sensitizes hypoxic HeLa cells to ionising radiation by mechanisms both dependent and independent of COX-2.

It is widely accepted that the hypoxic nature of solid tumors contribute to their resistance to radiation therapy. There is increasing evidence that cyclooxygenase-2 (COX-2) contributes to increased resistance of tumors to radiation therapy. Several studies demonstrate that combination of COX-2 selective inhibitors with radiation therapy selectively enhances radio responsiveness of tumor cells.

Journeying through the Field of Medicinal Chemistry: Perspectives from Graduate Researchers.

The training of new medicinal chemists is vital to the future of the field, and as graduate students at this critical stage, we are uniquely positioned to comment on our training. Herein, we discuss the perspectives from graduate researchers before, during, and after graduate school by utilizing survey data obtained from five medicinal chemistry programs in the Midwest and recent alumni of the University of Minnesota. We also reflect on the female perspective within the field of medicinal chemistry.

Developing a web-based patient decision aid for gastrostomy in motor neuron disease: a study protocol.

Introduction: Motor neuron disease (MND) is a progressive, incurable disease, characterised by degeneration of the nerves in the brain and spinal cord. Due to the multisystem effects of the disease, patients are faced with many complex, time-sensitive decisions, one of which is the decision on gastrostomy feeding. There are currently no published decision aids (DAs) to support patients making this decision in the UK.

Capture of biologic and biosimilar dispensings in a consortium of U.S.-based claims databases: Utilization of national drug codes and Healthcare Common Procedure Coding System modifiers in medical claims.

Purpose: To assess the capture of biologics (originator and biosimilar) in the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN), with a focus on medical claim National Drug Code (NDC), a new data field, and Healthcare Common Procedure Coding System (HCPCS) modifier.

Methods: We conducted a repeated cross-sectional study among patients with medical and pharmacy benefits enrolled in insurance plans participating in the BBCIC DRN between 1 January 2013 and 30 September 2017. We calculated the proportion of medical claims with ≥1 NDC and identified select biologics using four different approaches: (a) specific HCPCS alone, (b) specific HCPCS and NDC, (c) non-specific HCPCS with NDC, and (d) HCPCS with modifiers (applicable to biosimilars).

Interventions to promote oral nutritional behaviours in people living with neurodegenerative disorders of the motor system: A systematic review.

Background & Aims: Weight loss is common in people with neurodegenerative diseases of the motor system (NDMS), such as Parkinson's disease and Amyotrophic Lateral Sclerosis, and is associated with reduced quality of life, functional ability and survival. This systematic review aims to identify interventions and intervention components (i.e.

Correction to: Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease.

The original version of this article unfortunately contained a mistake. The numbers in the Table 5 appear to have been reproduced wrongly as dates, rather than percentages.

Comparing written and verbal delivery of a treatment regimen to women with overactive bladder: a randomized controlled trial.

Objective: Overactive bladder is a common condition among aging women requiring a multifaceted treatment approach, which is usually communicated by physician to the patient in the clinic setting. The objective of this two-center, randomized controlled trial was to determine if a transcribed list of six management strategies for overactive bladder improves immediate and delayed retention of these recommendations compared with a traditional verbal discussion.

Methods: Between March, 2015 and February, 2019, women newly diagnosed with overactive bladder were randomized to either the intervention group, where they received a transcribed list of six treatment recommendations, or to the control group, where the same six recommendations were communicated verbally by their physician.

Process evaluation and exploration of telehealth in motor neuron disease in a UK specialist centre.

Objectives: To evaluate the processes involved in using a novel digitally enabled healthcare system (telehealth in motor neuron disease (TiM)) in people living with motor neuron disease (MND) and their informal carers. We examined TiM implementation, potential mechanisms of impact and contextual factors that might influence TiM implementation or impact.

Design: An 18-month, single-centre process evaluation within a randomised, pilot and feasibility study.

Using telehealth in motor neuron disease to increase access to specialist multidisciplinary care: a UK-based pilot and feasibility study.

Objectives: Care of patients with motor neuron disease (MND) in a specialist, multidisciplinary clinic is associated with improved survival, but access is not universal. We wanted to pilot and establish the feasibility of a definitive trial of a novel telehealth system (Telehealth in Motor neuron disease, TiM) in patients with MND.

Design: An 18-month, single-centre, mixed-methods, randomised, controlled pilot and feasibility study.