Adapting nitric oxide: A review of its foundation, uses in austere medical conditions, and emerging applications.

Nitric oxide was first identified as a novel and effective treatment for persistent pulmonary hypertension of the newborn (PPHN), and has since been found to be efficacious in treating acute respiratory distress syndrome (ARDS) and pulmonary hypertension. Physicians and researchers have also found it shows promise in resource-constrained settings, both within and outside of the hospital, such as in high altitude pulmonary edema (HAPE) and COVID-19. The treatment has been well tolerated in these settings, and is both efficacious and versatile when studied across a variety of clinical environments.

A Geographical Analysis of Access to Trauma Centers from US National Parks in 2018.

Introduction: Millions of people visit US national parks annually to engage in recreational wilderness activities, which can occasionally result in traumatic injuries that require timely, high-level care. However, no study to date has specifically examined timely access to trauma centers from national parks. This study aimed to examine the accessibility of trauma care from national parks by calculating the travel time by ground and air from each park to its nearest trauma center.

Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients.

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator and mild bronchodilator that has been shown to improve systemic oxygenation, but has rarely been administered in the Emergency Department (ED). In addition to its favorable pulmonary vascular effects, in-vitro studies report that NO donors can inhibit replication of viruses, including SARS Coronavirus 2 (SARS-CoV-2). This study evaluated the administration of high-dose iNO by mask in spontaneously breathing emergency department (ED) patients with respiratory symptoms attributed to Coronavirus disease 2019 (COVID-19).

Siamit: A Novel Academic-Tribal Health Partnership in Northwest Alaska.

Problem: American Indians and Alaska Natives hold a state-conferred right to health, yet significant health and health care disparities persist. Academic medical centers are resource-rich institutions committed to public service, yet few are engaged in responsive, equitable, and lasting tribal health partnerships to address these challenges.

Approach: Maniilaq Association, a rural and remote tribal health organization in Northwest Alaska, partnered with Massachusetts General Hospital and Harvard Medical School to address health care needs through physician staffing, training, and quality improvement initiatives.

PF-06881894, a Proposed Biosimilar to Pegfilgrastim, Versus US-Licensed and EU-Approved Pegfilgrastim Reference Products (Neulasta): Pharmacodynamics, Pharmacokinetics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers.

Introduction: PF-06881894 is a proposed biosimilar to pegfilgrastim (Neulasta). This study evaluated the pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of PF-06881894 vs pegfilgrastim reference products (US- and EU-Neulasta) in healthy volunteers.

Methods: A phase 1, open-label, randomized, crossover study was conducted to assess the pharmacologic equivalence and safety of a single 6-mg dose of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU.

Incidence of Mild Cognitive Impairment with Ascending Altitude.

This study aimed to longitudinally quantify the prevalence of mild cognitive impairment (MCI) in individual trekkers at three different ascending altitudes (Site 1: ∼3500 m, Site 2: ∼4400 m, and Site 3: ∼5100 m). We correlated these findings with the presence of acute mountain sickness (AMS). We performed serial assays using the environmental quick mild cognitive impairment (eQMCI) score on 103 English-speaking 18- to 65-year-old volunteers trekking to Everest Base Camp in Nepal during spring 2016.

Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of High Altitude Headache and Acute Mountain Sickness.

Introduction: High altitude headache (HAH) and acute mountain sickness (AMS) are common pathologies at high altitudes. There are similarities between AMS and migraine headaches, with nausea being a common symptom. Several studies have shown ibuprofen can be effective for AMS prophylaxis, but few have addressed treatment.

A Phase 1, Randomized, Open-Label, Safety, Tolerability, and Comparative Bioavailability Study of Intranasal Dihydroergotamine Powder (STS101), Intramuscular Dihydroergotamine Mesylate, and Intranasal DHE Mesylate Spray in Healthy Adult Subjects.

Objective: To investigate and compare the safety and the pharmacokinetics of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), intranasal DHE spray (Migranal ), and intramuscular (IM) DHE injection in healthy subjects.

Methods: This was a 2-part, active-controlled, 3-period crossover study over 3 weeks, separated by 1-week washout periods. In part 1, 3 ascending dosage strengths of STS101 (1.

British Heart Rhythm Society Clinical Practice Guidelines on the Management of Patients Developing QT Prolongation on Antipsychotic Medication.

The British Heart Rhythm Society's are written for heart rhythm consultants, primary care physicians, specialist registrars, nurses and physiologists who may be requested to review ECGs or advise on cases where antipsychotic-induced QT prolongation is suspected or proven. The guidance is adapted from the latest Maudsley Prescribing Guidelines in Psychiatry, published in 2018.

Efficacy of late line pertuzumab with trastuzumab and chemotherapy in HER2-positive metastatic breast cancer: An Australian case series.

Background: Pertuzumab, when combined with trastuzumab and chemotherapy, is a highly active human epidermal growth factor receptor 2 (HER2), targeting agent in the neoadjuvant, adjuvant and first-line metastatic HER2-positive breast cancer setting. The efficacy of late-line (after first/second-line) pertuzumab in combination with trastuzumab and chemotherapy is unknown.

Aims: To establish pertuzumab efficacy by performing an audit of patients who received pertuzumab after first-line HER2 directed therapy.

Ultrasound in Austere Environments.

Ultrasonography is a noninvasive, reliable, repeatable, and inexpensive technology that has dramatically changed the practice of medicine. The clinical use of portable ultrasound devices has grown tremendously over the last 10 years in the fields of intensive care, emergency medicine, and anesthesiology. In this review we present the various ways that handheld portable ultrasound devices can be used in austere environments.

The use of a single chamber leadless pacemaker for the treatment of cardioinhibitory vasovagal syncope.

Background: The use of pacemakers in the treatment of cardioinhibitory vasovagal syncope is controversial with a mixed message from the limited evidence base. Single chamber leadless pacemakers have been shown to be an effective alternative option to conventional pacemakers.

Objective: This study examines the use of leadless pacemakers in a cardioinhibitory vasovagal population in the United Kingdom.

PF-06881893 (Nivestym™), a Filgrastim Biosimilar, Versus US-Licensed Filgrastim Reference Product (US-Neupogen): Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers.

Background: Three comparative clinical studies assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of PF-06881893 (filgrastim-aafi; Nivestym™), a filgrastim biosimilar, versus US-licensed reference product (filgrastim; US-Neupogen) in healthy volunteers (HVs).

Methods: Two separate open-label, crossover-design PK/PD studies were conducted: a single-dose study (n = 24) and a multiple-dose study (n = 60). In each study, HVs were randomized to Nivestym followed by US-Neupogen, or vice versa.

Recurrence in early breast cancer: Analysis of data from 3,765 Australian women treated between 1997 and 2015.

Background: Evidence suggests recent improvements in outcome in early breast cancer (EBC).

Aim: To analyse recurrence in women with EBC from our region from 1997 to 2015.

Methods: We analysed recurrence in 3,765 women with EBC.

A Thorough QT/QTc Study of Clobazam in Healthy Volunteers.

Purpose: A thorough QT study was conducted to assess the proarrhythmic potential of clobazam and its active metabolite, N-desmethylclobazam (N-CLB).

Methods: In this Phase I, single-site, randomized, double-blind, double-dummy, parallel-group study, healthy participants were randomized to 1 of 4 treatment groups: clobazam 40 mg/d (maximum therapeutic dosage), clobazam 160 mg/d (supratherapeutic dosage), placebo, or moxifloxacin 400 mg (active control).

Findings: Of 280 enrolled participants (n = 70 per treatment arm), 250 (92%) completed the study; 194 were included in the pharmacokinetics population (clobazam 40 mg/d, n = 66; clobazam 160 mg/d, n = 62; and moxifloxacin, n = 66).

Trends in Skin and Soft Tissue-Related Injuries in NOLS Wilderness Expeditions from 1984 to 2012.

Objective: Wilderness expeditions inevitably involve risk to participants. Understanding of expedition-related illnesses and injuries allows institutions and individuals to develop strategies to mitigate risk. We describe findings and trends in soft tissue injuries, the second-most common type of injury, among participants in the National Outdoor Leadership School expeditions from 1984 to 2012.

Vigabatrin Lacks Proarrhythmic Potential: Results from a Thorough QT/QTc Study in Healthy Volunteers.

Purpose: A thorough QT study was performed to assess the proarrhythmic potential of vigabatrin, an antiepileptic drug approved in the United States for the treatment of infantile spasms and refractory complex partial seizures.

Methods: In this Phase I, randomized, double-blind, placebo- and active-controlled (moxifloxacin), 4-sequence, crossover study conducted at a single center, healthy participants received 1 of 4 randomly assigned treatments: 3.0g vigabatrin solution (therapeutic dose) and 1 moxifloxacin placebo tablet; 6.

Effects of a New Hospital-Wide Surgical Consultation Protocol in Patients with Clostridium difficile Colitis.

Background: Fulminant Clostridium difficile colitis (fCDC) occurs in 2%-8% of patients with CDC and carries a high death rate. Prompt operation may reduce death. Our aim was to determine whether a standardized hospital-wide protocol for surgical referral in CDC would result in earlier surgical consultation, earlier identification of patients who could benefit from surgical therapy, and reduced deaths from fCDC.