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Journal For Immunotherapy of Cancer May 2021COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute...
COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.
Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; COVID-19; Cytokine Release Syndrome; Humans; Immunization, Passive; Immunotherapy; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-6; Nitriles; Pyrazoles; Pyrimidines; SARS-CoV-2; Tumor Necrosis Factor-alpha; COVID-19 Serotherapy; COVID-19 Drug Treatment
PubMed: 33986127
DOI: 10.1136/jitc-2021-002392 -
European Review For Medical and... Apr 2021Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs)...
OBJECTIVE
Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs) are the treatment of choice. The objective of this study was to identify potential interactions between DMARDs and the drugs most frequently prescribed in dentistry in order to avoid adverse reactions.
MATERIALS AND METHODS
This literature review sets out to define possible adverse reactions provoked by pharmacological interactions between DMARDs and the drugs commonly prescribed in dentistry. A search was conducted in PubMed by searching the names of drugs used in dentistry, "drug interactions," "rheumatoid arthritis," and "dentistry", "hydroxychloroquine", "leflunomide", "methotrexate", "sulfasalazine", "adalimumab", "anakinra", "etanercept", "abatacept", "infliximab" and "rituximab".
RESULTS
It was found that most DMARDs show potential interactions with many drugs used in dentistry, including various antibiotics, analgesics, anesthetics, antifungals, and corticosteroids.
CONCLUSIONS
It is clinically important for oral health clinicians to be aware of possible drug interactions between DMARDs and the drugs commonly prescribed in dentistry to prevent potential adverse reactions and avoid endangering the patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Interactions; Humans
PubMed: 33877648
DOI: 10.26355/eurrev_202104_25536 -
Annals of the Rheumatic Diseases Jun 2021To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.
OBJECTIVE
To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.
METHODS
As part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools.
RESULTS
Of the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vilobelimab. Glucocorticoids were able to reduce mortality in specific subsets of patients, while conflicting data were available about tocilizumab. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials on some other compounds provided interesting, although preliminary, results.
CONCLUSION
Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.
Topics: COVID-19; Glucocorticoids; Humans; Hydroxychloroquine; Immunization, Passive; Interleukin 1 Receptor Antagonist Protein; Rheumatic Diseases; SARS-CoV-2; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33589438
DOI: 10.1136/annrheumdis-2020-219725 -
Mediators of Inflammation 2021We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary... (Meta-Analysis)
Meta-Analysis
METHODS
We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary artery disease patients. We searched the electronic database until March 2020 for relevant studies.
RESULTS
Nineteen trials examining the efficacy of eight anti-inflammatory medications (pexelizumab, anakinra, colchicine, darapladib, varespladib, canakinumab, inclacumab, and losmapimod) were selected for analysis. Overall, there is no statistically significant difference in all-cause mortality, cardiovascular mortality, revascularization, and major cardio and cerebrovascular events (MACCE) with the use of anti-inflammatory drugs. However, we found the use of colchicine significantly reduces the odds of developing stroke by approximately 75% (OR 0.26, CI 0.10-0.63). Colchicine use was also associated with a lower risk of revascularization and MACCE compared to the other agents. Our subgroup analyses comparing the timing of medication initiation (within 7 days vs. >7 days) and clinical presentation (ACS vs. non-ACS) revealed a significant reduction in the risk of recurrent MI in the group that received medication after seven days (OR 0.92, CI 0.86-0.99) and the non-ACS group (OR 0.88, CI 0.80-0.98).
CONCLUSION
Although many anti-inflammatory medications have failed to reduce adverse cardiovascular outcomes in the CAD population, selected medications show promise among subgroups of patients without ACS or after the first week following an acute ischemic event. Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted.
Topics: Adult; Aged; Anti-Inflammatory Agents; Colchicine; Comparative Effectiveness Research; Coronary Circulation; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 33510581
DOI: 10.1155/2021/5160728 -
Psychopharmacology Feb 2021Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management...
RATIONALE
Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics.
EVIDENCE REVIEW
Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted.
RESULTS
The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone.
CONCLUSIONS
Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.
Topics: Antipsychotic Agents; Antiviral Agents; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Long QT Syndrome; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 33410987
DOI: 10.1007/s00213-020-05716-4 -
PLoS Medicine Dec 2020Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective.
METHODS AND FINDINGS
We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527).
CONCLUSIONS
In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Azithromycin; COVID-19; Critical Illness; Hospitalization; Humans; Hydroxychloroquine; Immunization, Passive; Network Meta-Analysis; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33378357
DOI: 10.1371/journal.pmed.1003501 -
Laryngoscope Investigative... Dec 2020The study systematically reviewed the existing literature on the management of autoimmune inner ear disease (AIED). (Review)
Review
OBJECTIVES
The study systematically reviewed the existing literature on the management of autoimmune inner ear disease (AIED).
STUDY DESIGN
Systematic review.
METHODS
We performed a literature search of Embase, NCBI, Cochrane, and Web of Science databases from April 1990 to April 2020. Inclusion criteria included studies that were retrospective or prospective in nature evaluating the treatment of AIED with audiometric data measuring hearing outcomes during treatment. Hearing improvement was the primary study outcome and improvement in vestibular symptoms was the secondary study outcome.
RESULTS
Sixteen of 412 candidate articles were included in our study. Systemic steroid treatment is most commonly described. Alternative treatment modalities included intratympanic steroid treatment, methotrexate, cyclophosphamide, azathioprine, infliximab, etanercept, adalimumab, golimumab, methylprednisolone, rituximab, and anakinra.
CONCLUSION
Systemic corticosteroids are the first line treatment of AIED. Intratympanic steroids are a potential adjuvant or alternative treatment for patients who cannot tolerate or become refractory to steroid treatment. Steroid nonresponders may benefit from biologic therapy. Alternative treatment modalities including nonsteroidal immunosuppressants and biologics have been studied in small cohorts of patients with varying results. Prospective studies investigating the efficacy of biologic and nonsteroidal therapy are warranted.
LEVEL OF EVIDENCE
2.
PubMed: 33364414
DOI: 10.1002/lio2.508 -
Scientific Reports Dec 2020Plant-based diets like vegetarian or vegan diets might influence circulating levels of inflammatory biomarkers, thereby reducing the risk of chronic diseases. This... (Comparative Study)
Comparative Study Meta-Analysis
Plant-based diets like vegetarian or vegan diets might influence circulating levels of inflammatory biomarkers, thereby reducing the risk of chronic diseases. This systematic review and meta-analysis aimed to investigate the associations of veganism and vegetarianism with circulating inflammatory biomarkers in comparison to omnivores. Literature search was conducted in Pubmed and EMBASE until April 2020 and mean differences of biomarkers were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1 receptor antagonist (IL-1 RA), tumor necrosis factor-alpha (TNF-ɑ), E-selectin, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), adiponectin, omentin-1 and resistin. Of initially identified 1073 publications, 21 cross-sectional studies met the inclusion criteria and were included in the systematic review and meta-analysis. Vegan diet was associated with lower levels of CRP compared to omnivores [mean difference - 0.54 mg/l, 95%-CI: - 0.79 to - 0.28, p < 0.0001]. This association was less pronounced in vegetarians [mean difference - 0.25 mg/l, 95%-CI: - 0.49 to 0.00, p = 0.05]. In patients with impaired kidney function, the association between vegetarian nutrition and CRP was much stronger with - 3.91 mg/l (95%-CI: - 5.23 to - 2.60; p < 0.0001). No substantial effects were observed for all other inflammatory biomarkers. Despite strong associations between CRP and a vegan or vegetarian diet were seen, further research is needed, as most inflammatory biomarkers were investigated only in single studies so far.
Topics: Biomarkers; C-Reactive Protein; Chronic Disease; Diet, Vegan; Diet, Vegetarian; Inflammation; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-18; Interleukin-6
PubMed: 33303765
DOI: 10.1038/s41598-020-78426-8 -
Drugs Dec 2020Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19...
BACKGROUND
Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated.
OBJECTIVES
The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported.
METHODS
The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020.
RESULTS
After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive.
CONCLUSIONS
Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Biological Products; COVID-19; Cytokines; Dexamethasone; Drug Therapy, Combination; Humans; Inflammation Mediators; Intensive Care Units; Pandemics; Retrospective Studies; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33068263
DOI: 10.1007/s40265-020-01421-w -
Cardiology in ReviewInflammation of the pericardium (pericarditis) is characterized by excruciating chest pain. This systematic literature review summarizes clinical, humanistic, and...
Inflammation of the pericardium (pericarditis) is characterized by excruciating chest pain. This systematic literature review summarizes clinical, humanistic, and economic burdens in acute, especially recurrent, pericarditis, with a secondary aim of understanding United States treatment patterns and outcomes. Short-term clinical burden is well characterized, but long-term data are limited. Some studies report healthcare resource utilization and economic impact; none measure health-related quality-of-life. Pericarditis is associated with infrequent but potentially life-threatening complications, including cardiac tamponade (weighted average: 12.7% across 10 studies), constrictive pericarditis (1.84%; 9 studies), and pericardial effusion (54.7%; 16 studies). There are no approved pericarditis treatments; treatment guidelines, when available, are inconsistent on treatment course or duration. Most recommend first-line use of conventional treatments, for example, nonsteroidal antiinflammatory drugs with or without colchicine; however, 15-30% of patients experience recurrence. Second-line therapy may involve conventional therapies plus long-term utilization of corticosteroids, despite safety issues and the difficulty of tapering or discontinuation. Other exploratory therapies (eg, azathioprine, immunoglobulin, methotrexate, anakinra) present steroid-sparing options, but none are supported by robust clinical evidence, and some present tolerability challenges that may impact adherence. Pericardiectomy is occasionally pursued in treatment-refractory patients, although data are limited. This lack of an evidence-based treatment pathway for patients with recurrent disease is reflected in readmission rates, for example, 12.2% at 30 days in 1 US study. Patients with continued recurrence and inadequate treatment response need approved, safe, accessible treatments to resolve pericarditis symptoms and reduce recurrence risk without excessive treatment burden.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chest Pain; Humans; Pericardial Effusion; Pericarditis; United States
PubMed: 32956167
DOI: 10.1097/CRD.0000000000000356