Calcitonin gene-related peptide (CGRP) is a vasodilatory peptide that has been detected at high levels in the skin, blood, and cerebrospinal fluid (CSF) under a variety of inflammatory and chronic pain conditions, presumably derived from peptidergic C and Aδ innervation. Herein, CGRP immunolabeling (IL) was detected in epidermal keratinocytes at levels that were especially high and widespread in the skin of humans from locations afflicted with postherpetic neuralgia (PHN) and complex region pain syndrome type 1 (CRPS), of monkeys infected with simian immunodeficiency virus, and of rats subjected to L5/L6 spinal nerve ligation, sciatic nerve chronic constriction, and subcutaneous injection of complete Freund's adjuvant. Increased CGRP-IL was also detected in epidermal keratinocytes of transgenic mice with keratin-14 promoter driven overexpression of noggin, an antagonist to BMP-4 signaling. ⋯ Cutaneous peptidergic innervation has been shown to express predominantly the alpha isoform of CGRP. Keratinocytes also express the cognate CGRP receptor components, Calcitonin receptor-like receptor (CRLR), Receptor activity-modifying protein 1 (RAMP1), CGRP-receptor component protein (RCP) consistent with known observations that CGRP promotes several functional changes in keratinocytes, including proliferation and cytokine production. Our results indicate that keratinocyte-derived CGRPβ may modulate epidermal homeostasis through autocrine/paracrine signaling and may contribute to chronic pain under pathological conditions.
Randomized Controlled Trial Multicenter Study Clinical Trial
Why do we need another PPE review?
This review contextualises the PPE issues with their (relatively low quality) evidence base, focusing particularly on anaesthesia given that this is a high-risk occupational group. Coming from both a UK expert and journal, the recommendations should be carefully considered in terms of the UK's severe COVID outbreak and PPE supply issues.
- The significance of airborne transmission, in particular the infectivity of airborne viral particles beyond 1 meter, is uncertain.
- PPE should be seen as an important and essential part of a larger safety system.
- Intubation is a high-risk procedure for aerosol generation. A ventilated negative pressure room and airborne-precaution PPE is recommended. Ventilation (frequency of air-exchange) is likely more important than negative pressure.1 Chinese evidence suggests COVID transmission at intubation is low with appropriate PPE, although there is wide variability in extremes of PPE used along with post-exposure disinfection (eg. showering).
- High-flow nasal oxygen and supraglottic airway (eg. LMA) placement may also be aerosol generating.
- Most risk of transmission from sneezing and coughing is probably droplet and contact, rather than airborne, although the science behind these questions are complex and uncertain. Evidence attempting to answer these questions is often from non-clinical settings.
- Fluid-resistant surgical masks when worn by staff may reduce transmission by at least 80%. Superiority of respirator masks (eg. P2,P3,N95) is not yet reliably supported by evidence.
- Cook highlights two main PPE problems: 1. PPE supply; 2. Inappropriate use of PPE (using higher level than required).
- PPE should be simple to remove (doff) after use, to reduce contamination risk. Cook notes that Canada's SARS experience highlighted increased risk of self contamination with more complex PPE.
On specific levels of PPE
- Contact precautions (gloves & gown) are recommended when in vicinity of COVID positive patient but not within 2 meters.
- Droplet precautions (+ mask & eye protecting) are recommended within 2 meters of patients.
- Airborne precautions (+ FFP3 respirator mask) are only recommended for aerosol generating procedures (AGP). However classification of procedures as AGP or not is only loosely evidence based.
"Public Health England recommends airborne precautions are used in ‘hot spots’ where aerosol generating procedure are regularly performed, if any suspected COVID-19 patients are present – these include intensive care unit, operating theatre, emergency department resuscitation bays and labour wards where mothers are in stage 2 or 3 of labour"
The elephant in the room is that the lack of PPE supply appears to be the main driver of the rapidly-changing PPE recommendations.
PPE choices need to be made in consideration of the spectrum of risk, hazard and cost, acknowledging different risk profiles depending on location, procedure and individual clinicians.
It's worth highlighting that negative pressure confers no protection on those in the room, it's purpose is to prevent escape of contagion to areas outside the room. ↩
Randomized Controlled Trial Comparative Study
Ultrasound (US)-guided subclavian vein (SCV) catheterization via the supraclavicular (SC) or infraclavicular (IC) approaches can be useful in children. The purpose of this study was to compare the efficacy of these approaches. ⋯ During SCV catheterization under US guidance in paediatric patients, the SC approach yielded a shorter puncture time and decreased the incidence of guidewire misplacement when compared with the IC approach.