Should we be concerned when COVID-19-positive patients take opioids to control their pain? Insights from a pharmacological point of view

Objective: The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches. Materials and methods: Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language. Results: Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters. Conclusions: Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder

Coupled plasma filtration and adsorption in septic shock: a multicentric experience

Introduction Recently extracorporeal removal of mediators and endotoxins improved haemodynamics, organ dysfunction and mortality in patients with abdominal sepsis [1]. Coupled plasma filtration and adsorption (CPFA), too, may improve haemodynamics, respiratory function and mortality through removal of proinfl ammatory mediator. The aim of this multicentric study is to evaluate the haemodynamic response and the respiratory function, and to evaluate the reduction of infl ammatory markers during CPFA.Methods Fifty-fi ve septic patients were enrolled in this study. Every patient had four CPFA treatments (LINDA; Bellco-Mirandola, Italy) for 8 hours with Qb = 200 ml/minute, Qultrafi ltration = 30 ml/kg/hour and Qplasma = 20% of Q b. At T0 (basal), T1 (after fi rst cycle), T2 (after second cycle), T3 (after third cycle)and T4 (after fourth cycle) we evaluated haemodynamic parameters, norepinephrine dosage, PaO2/FiO 2 ratio, plasma IL-6, and procalcitonin (PCT). The ANOVA test was used to compare changes during times study. P <0.05 was considered statistically significant. Results Patients enrolled in the study have been submitted to 256 CPFA treatments for 2,650 hours. Table 1 presents the main results of the study. IV quartile of IL-6 is shown in Table 1Conclusions In this large multicentric study, CPFA may improve haemodynamic status and respiratory function. Plasma fi ltration and adsorption of proinfl ammatory mediators may explain this improvement. Larger randomized controlled trials are indicated to confi rm these data. Reference 1.Cruz D, et al.: JAMA 2009, 23:2445-2452

The Influence of Age at Pediatric-Onset Spinal Cord Injury and Years of Wheelchair Use on Shoulder Complex Joint Dynamics During Manual Wheelchair Propulsion

Objective To assess the association of age at pediatric-onset spinal cord injury (SCI) and years of manual wheelchair use with shoulder dynamics. Design Upper extremity kinematics and hand-rim kinetics were obtained during manual wheelchair propulsion. An inverse dynamics model computed three-dimensional acromioclavicular, sternoclavicular, and glenohumeral joint dynamics. Linear mixed effects models evaluated the association of age at injury onset and years of wheelchair use with shoulder dynamics. Setting Motion laboratory within a children\u27s hospital. Participants Seventeen manual wheelchair users (N=17; 6 female, 11 male; mean age: 17.2 years, mean age at SCI onset: 11.5 years) with pediatric-onset SCI (levels: C4-T11) and International Standards for Neurological Classification of SCI grades: A (11), B (3), C (2), and N/A (2). Interventions Not applicable. Main Outcome Measures Acromioclavicular, sternoclavicular, and glenohumeral angles and ranges of motion, and glenohumeral forces and moments. Results We observed a decrease in maximum acromioclavicular upward rotation (ß [95% confidence interval {CI}]=3.02 [0.15,5.89], P=.039) and an increase in acromioclavicular downward/upward rotation range of motion (ß [95% CI]=0.44 [0.08,0.80], P=.016) with increasing age at SCI onset. We found interactions between age at onset and years of use for maximum glenohumeral abduction (ß [95% CI]=0.16 [0.03,0.29], P=.017), acromioclavicular downward/upward rotation range of motion (ß [95% CI]=-0.05 [-0.09,-0.01], P=.008), minimum acromioclavicular upward rotation (ß [95% CI]=-0.34 [-0.64,-0.04], P=.026). A decrease in glenohumeral internal rotation moment (ß [95% CI]=-0.09 [-0.17,-0.009], P=.029) with increasing years of use was found. Conclusions Age at injury and the years of wheelchair use are associated with shoulder complex biomechanics during wheelchair propulsion. These results are noteworthy, as both age at SCI onset and years of wheelchair use are considered important factors in the incidence of shoulder pain. These results suggest that investigations of biomechanical changes over the lifespan are critical

“Salus Populi Suprema Lex”: Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis

Incidence of pneumomediastinum in COVID-19: A single-center comparison between 1st and 2nd wave

In this study, we compared the incidence of pneumomediastinum in coronavirus disease (COVID-19) patients during the ascending phases of the 1st and 2nd epidemic waves. Crude incidence was higher during the 2nd wave at a quasi-significant level (0.68/1000 vs. 2.05/1000 patient-days, p = 0.05). When restricting the analysis to patients who developed pneumomediastinum during noninvasive ventilation, the difference became clearly significant (0.17/1000 vs 1.36/1000 patient-days, p = 0.039). At logistic regression, predisposing factors (p = 0.031), and COVID-19 radiological severity (p = 0.019) were independently associated with pneumomediastinum. Mortality in patients with pneumomediastinum was 87.5%. However, pneumomediastinum seemed to be related to a generally worse disease presentation in hospitalized patients during the 2nd wave, rather than to a separate pattern of disease. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved

The combined use of VIGl@ct (R) (bioMerieux) and fluorescent amplified length fragment polymorphisms in the investigation of potential outbreaks

Even with good surveillance programmes, hospital-acquired infections (HAls) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAls, based on the use of a real-time epidemiological information system called VIGI@ct (R) (bioMerieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total, of 306 suspicious HAls. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the tatter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESPL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct (R) and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gramnegative bacteria and yeasts. (C) 2007 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved