Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial.

Background: Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B treatment, was shown to be superior to treatment with continuous prophylactic factor IX in terms of bleeding protection 18 months after gene therapy in a phase 3 trial. We report post-hoc 24-month efficacy and safety data from this trial to evaluate the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B.

Methods: The phase 3 HOPE-B trial enrolled males aged 18 years or older with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), with a severe bleeding phenotype and who were on stable continuous factor IX prophylaxis.

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials.

Importance: Flortaucipir positron emission tomography (PET) scans, rated with a novel, US Food and Drug Administration-approved, clinically applicable visual interpretation method, provide valuable information regarding near-term clinical progression of patients with Alzheimer disease (AD) or mild cognitive impairment (MCI).

Objective: To evaluate the association between flortaucipir PET visual interpretation and patients' near-term clinical progression.

Design/setting/participants: Two prospective, open-label, longitudinal studies were conducted from December 2014 to September 2019.

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia.

The advent of tau-targeted PET tracers such as flortaucipir (18F) (flortaucipir, also known as 18F-AV-1451 or 18F-T807) have made it possible to investigate the sequence of development of tau in relationship to age, amyloid-β, and to the development of cognitive impairment due to Alzheimer's disease. Here we report a multicentre longitudinal evaluation of the relationships between baseline tau, tau change and cognitive change, using flortaucipir PET imaging. A total of 202 participants 50 years old or older, including 57 cognitively normal subjects, 97 clinically defined mild cognitive impairment and 48 possible or probable Alzheimer's disease dementia patients, received flortaucipir PET scans of 20 min in duration beginning 80 min after intravenous administration of 370 MBq flortaucipir (18F).

Development of an imaging mitigation strategy for patient enrolment in the tanezumab nerve growth factor inhibitor (NGF-ab) program with a focus on eligibility assessment.

Objective: Nerve growth factor antibodies (NGF-ab) have shown promising analgesic efficacy. Aim was to describe reader training efforts and present reliability data focusing on radiographic eligibility in the tanezumab program.

Methods: A multi-step process was used for reader calibration and reliability testing.

Impact of lower body negative pressure induced hypovolemia on peripheral venous pressure waveform parameters in healthy volunteers.

Lower body negative pressure (LBNP) creates a reversible hypovolemia by sequestrating blood volume in the lower extremities. This study sought to examine the impact of central hypovolemia on peripheral venous pressure (PVP) waveforms in spontaneously breathing subjects. With IRB approval, 11 healthy subjects underwent progressive LBNP (baseline, -30, -75, and -90 mmHg or until the subject became symptomatic).

Optimizing radiologist e-prescribing of CT oral contrast agent using a protocoling portal.

Objective: The purpose of this study is to quantify the time expenditure associated with radiologist ordering of CT oral contrast media when using an integrated protocoling portal and to determine radiologists' perceptions of the ordering process.

Subjects And Methods: This prospective study was performed at a large academic tertiary care facility. Detailed timing information for CT inpatient oral contrast orders placed via the computerized physician order entry (CPOE) system was gathered over a 14-day period.

Impact of central hypovolemia on photoplethysmographic waveform parameters in healthy volunteers part 2: frequency domain analysis.

Objective: The photoplethysmographic (PPG) waveforms are modulated by the respiratory, cardiac and autonomic nervous system. Lower body negative pressure (LBNP) has been used as an experimental tool to simulate loss of central blood volume in humans. The aim of our research is to understanding PPG waveform changes during progressive hypovolemia.

Impact of central hypovolemia on photoplethysmographic waveform parameters in healthy volunteers. Part 1: time domain analysis.

Introduction: Our study sought to explore changes in photoplethysmographic (PPG) waveform param- eters, during lower body negative pressure (LBNP) which simulated hypovolemia, in spontaneously breathing volunteers. We hypothesize that during progressive LBNP; there will be a preservation of ear PPG parameters and a decrease in finger PPG parameters.

Methods: With IRB approval, 11 volunteers underwent a LBNP protocol at baseline, 30, 75, and 90 mm Hg (or until the subject became symptomatic).

A novel approach using time-frequency analysis of pulse-oximeter data to detect progressive hypovolemia in spontaneously breathing healthy subjects.

Accurate and early detection of blood volume loss would greatly improve intraoperative and trauma care. This study has attempted to determine early diagnostic and quantitative markers for blood volume loss by analyzing photoplethysmogram (PPG) data from ear, finger and forehead sites with our high-resolution time-frequency spectral (TFS) technique in spontaneously breathing healthy subjects (n = 11) subjected to lower body negative pressure (LBNP). The instantaneous amplitude modulations present in heart rate (AM HR) and breathing rate (AMBR) band frequencies of PPG signals were calculated from the high-resolution TFS.

Tissue Doppler of early mitral filling correlates with simulated volume loss in healthy subjects.

Objectives: The accurate noninvasive assessment of preload in emergency department (ED) patients remains elusive. Point-of-care ultrasound (US) imaging, particularly evaluation of the inferior vena cava (IVC), has been shown to be qualitatively helpful. Doppler and tissue Doppler are now routinely available on ED US equipment, but few studies have looked at the correlation of dynamic changes in these parameters in a controlled model of hypovolemia.

Can emergency medical dispatch systems safely reduce first-responder call volume?

Objectives: Emergency medical dispatch (EMD) protocols are intended to match response resources with patient needs. In a small city that previously sent a first-responder basic life support (BLS) engine company lights-and-siren response to every emergency medical services (EMS) call, regardless of nature or severity, an EMD system was implemented in order to reduce the number of such responses. The study objectives were to determine the effects of the EMD system on first-responder call volume and to assess the safety of the system.

Direct intraosseous pressure monitoring of the femoral head during surgery for slipped capital femoral epiphysis.

Preventing avascular necrosis following surgical management of pediatric slipped capital femoral epiphysis is a critical goal. The direct intraosseous pressure monitor is a readily available and affordable technique that can easily be used by surgeons around the world.

Is there a role for first responders in EMS responses to medical facilities?

Objective: Emergency medical dispatch (EMD) protocols should match response resources with patient needs. We tested a protocol sending only a commercial ambulance, without fire department first responders (FR), to all non-cardiac-arrest EMS calls at a physician-staffed HMO facility. Study objectives were to determine how often FR provided patient care at such facilities and whether EMD implementation could conserve FR resources without compromising patient care.