Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory ...syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab's therapeutic effects in patients with life-threatening SARS-CoV-2 infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the ...short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO
clearance after 2 h of treatment.
We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO
≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO
from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO
at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes.
Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO
reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO
reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO
reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis.
HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO
after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD.
The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).
To identify emerging mental health problems, strategies to address them, and opportunities to reform mental health systems during the COVID-19 pandemic in South America.
An online questionnaire was ...sent to mental health decision-makers of ministries of health in 10 South American countries in mid-April 2020. The semi-structured questionnaire had 12 questions clustered into three main sections: emerging challenges in mental health, current and potential strategies to face the pandemic, and key elements for mental health reform. We identified keywords and themes for each section through summative content analysis.
Increasing mental health burden and needs were reported as direct and indirect consequences of the COVID-19 pandemic. National lockdowns challenge the delivery and access to mental health treatment and care. Strategies to meet mental health needs rely heavily on timely and adequate responses by strengthened mental health governance and systems, availability of services, virtual platforms, and appropriate capacity-building for service providers. Short- and medium-term strategies focused on bolstering community-based mental health networks and telemedicine for high-risk populations. Opportunities for long-term mental health reform entail strengthening legal frameworks, redistribution of financial resources, and collaboration with local and international partners.
Mental health and psychosocial support have been identified as a priority area by South American countries in the COVID-19 response. The pandemic has generated specific needs that require appropriate actions, including implementing virtual interventions, orienting capacity-building toward protecting users and health providers, strengthening evidence-driven decision-making, and integrating mental health and psychosocial support in high-level mechanisms guiding the response to COVID-19.
Abstract
Background
Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. ...To date, little is known about the clearance effects of oscillating devices on patients with acute respiratory failure undergoing iMV. This study aimed to assess (1) the effects of high-frequency chest wall oscillation (HFCWO) on lung aeration and ventilation distribution, as assessed by electrical impedance tomography (EIT), and (2) the effect of the association of HFCWO with recruitment manoeuvres (RM).
Methods
Sixty critically ill patients, 30 classified as normosecretive and 30 as hypersecretive, who received ≥ 48 h of iMV, underwent HFCWO; patients from both subgroups were randomized to receive RM or not, according to two separated randomization sequences. We therefore obtained four arms of 15 patients each. After baseline record (T0), HFCWO was applied for 10 min. At the end of the treatment (T1) or after 1 (T2) and 3 h (T3), EIT data were recorded. At the beginning of each step, closed tracheobronchial suctioning was performed. In the RM subgroup, tracheobronchial suctioning was followed by application of 30 cmH
2
O to the patient’s airway for 30 s. At each step, we assessed the change in end-expiratory lung impedance (ΔEELI) and in tidal impedance variation (ΔTIV), and the center of gravity (COG) through EIT. We also analysed arterial blood gases (ABGs).
Results
ΔTIV and COG did not differ between normosecretive and hypersecretive patients. Compared to T0, ΔEELI significantly increased in hypersecretive patients at T2 and T3, irrespective of the RM; on the contrary, no differences were observed in normosecretive patients. No differences of ABGs were recorded.
Conclusions
In hypersecretive patients, HFCWO significantly improved aeration of the dorsal lung region, without affecting ABGs. The application of RM did not provide any further improvements.
Trial registration
Prospectively registered at the Australian New Zealand Clinical Trial Registry (
www.anzctr.org.au
; number of registration: ACTRN12615001257550; date of registration: 17th November 2015).
BACKGROUND:Assessing the volemic status of patients undergoing surgery is part of the routine management for the anesthesiologist. This assessment is commonly performed by means of dynamic indexes ...based on the cardiopulmonary interaction during mechanical ventilation (if available) or by administering a fluid challenge (FC). The FC is used during surgery to optimize predefined hemodynamic targets, the so-called Goal-Directed Therapy (GDT), or to correct hemodynamic instability (non-GDT).
METHODS:In this systematic review, we considered the FC components in studies adopting either GDT or non-GDT, to assess whether differences exist between the 2 approaches. In addition, we performed a meta-analysis to ascertain the effectiveness of dynamic indexes pulse pressure variation (PPV) and stroke volume (SV) variation (SVV), in predicting fluid responsiveness.
RESULTS:Thirty-five non-GDT and 33 GDT studies met inclusion criteria, including 5017 patients. In the vast majority of non-GDT and GDT studies, the FC consisted in the administration of colloids (85.7% and 90.9%, respectively). In 29 non-GDT studies, the colloid infused was the 6% hydroxyethyl starch (6% HES; 96.6% of this subgroup). In 20 GDT studies, the colloid infused was the 6% HES (66.7% of this subgroup), while in 5 studies was a gelatin (16.7% of this subgroup), in 3 studies an unspecified colloid (10.0% of this subgroup), and in 1 study albumin (3.3%) or, in another study, both HES 6% and gelatin (3.3%). In non-GDT studies, the median volume infused was 500 mL; the time of infusion and hemodynamic target to assess fluid responsiveness lacked standardization. In GDT studies, FC usually consisted in the administration of 250 mL of colloids (48.8%) in 10 minutes (45.4%) targeting an SV increase >10% (57.5%). Only in 60.6% of GDT studies, a safety limit was adopted. PPV pooled area under the curve (95% confidence interval CI) was 0.86 (0.80–0.92). The mean (standard deviation) PPV threshold predicting fluid responsiveness was 10.5% (3.2) (range, 8%–15%), while the pooled (95% CI) sensitivity and specificity were 0.80 (0.74–0.85) and 0.83 (0.73–0.91), respectively. SVV pooled area under the curve (95% CI) was 0.87 (0.81–0.93). The mean (standard deviation) SVV threshold predicting fluid responsiveness was 11.3% (3.1) (range, 7.5%–15.5%), while the pooled (95% CI) sensitivity and specificity were 0.82 (0.75–0.89) and 0.77 (0.71–0.82), respectively.
CONCLUSIONS:The key components of FC including type of fluid (colloids, often 6% HES), volume (500 and 250 mL in non-GDT studies and GDT studies, respectively), and time of infusion (10 minutes) are quite standardized in operating room. However, pooled sensitivity and specificity of both PPV and SVV are limited.
During flexible fiberoptic bronchoscopy (FOB) the arterial partial pressure of oxygen can drop, increasing the risk for respiratory failure. To avoid desaturation episodes during the procedure ...several oxygenation strategies have been proposed, including conventional oxygen therapy (COT), high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV). By a review of the current literature, we merely describe the clinical practice of oxygen therapies during FOB. We also conducted a pooled data analysis with respect to oxygenation outcomes, comparing HFNC with COT and NIV, separately. COT showed its benefits in patients undergoing FOB for broncho-alveolar lavage (BAL) or brushing for cytology, in those with peripheral arterial oxyhemoglobin saturation < 93% prior to the procedure or affected by obstructive disorder. HFNC is preferable over COT in patients with mild to moderate acute respiratory failure (ARF) undergoing FOB, by improving oxygen saturation and decreasing the episodes of desaturation. On the opposite, CPAP and NIV guarantee improved oxygenation outcomes as compared to HFNC, and they should be preferred in patients with more severe hypoxemic ARF during FOB.
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Coronavirus disease (COVID-19) not only has a long-term effect on its survivors, it also affects their quality of life, including inducing depression as a possible manifestation of central nervous ...system disruption. Favipiravir shows promising efficacy as an antiviral drug for the treatment of COVID-19. However, its effect on the sequelae of COVID-19 has not been explored. Therefore, this study aims to assess the impact of Favipiravir and address the factors associated with post-COVID depression in Indonesia.
This cohort study conducted a post-COVID-19 survey on Indonesian patients who were diagnosed by using real-time polymerase chain reaction (RT-PCR) and antigen tests until January 2022. An online questionnaire was distributed to obtain information on demographics, comorbidities, health behavior, symptoms, and treatment. The propensity technique was used to allocate the participants into the favipiravir and nonrecipient groups (1:1). The Patient Health Questionnaire-9 (PHQ-9) was used for outcome measurement. The cohort was followed up biweekly for 60 days after onset/diagnosis to determine the occurrence of depression. Cox regression analysis with an adjusted odds ratio and 95% confidence interval was used to estimate the effect of favipiravir on post-COVID-19 depression.
The data included the information of 712 participants, of whom 18.54% had depression within 60 days after onset/diagnosis. Depression was higher in the nonrecipient group (21.06%) than in the favipiravir group (16.01%). After adjustment by other factors, favipiravir prescription was found to be associated with depression (aOR 0.488, 95% CI 0.339-0.701 p < 0.001). In accordance with the PHQ-9 subset, favipiravir exerted a significant protective effect against depressive mood and loss of interest. However, patients living alone were prone to experiencing loss of interest (aOR 2.253, 95% CI 1.329-3.818, p = 0.003).
The data obtained in this preliminary survey suggested that favipiravir may be useful for preventing post-COVID depression. However, further study is needed. Moreover, the provision of mental health support, particularly to those who live alone, must be ensured.
Registry NCT05060562.
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Noninvasive ventilation (NIV) is generally delivered using pneumatically-triggered and cycled-off pressure support (PS
) through a mask. Neurally adjusted ventilatory assist (NAVA) is the only ...ventilatory mode that uses a non-pneumatic signal, i.e., diaphragm electrical activity (EAdi), to trigger and drive ventilator assistance. A specific setting to generate neurally controlled pressure support (PS
) was recently proposed for delivering NIV by helmet. We compared PS
with PS
and NAVA during NIV using a facial mask, with respect to patient comfort, gas exchange, and patient-ventilator interaction and synchrony.
Three 30-minute trials of NIV were randomly delivered to 14 patients immediately after extubation to prevent post-extubation respiratory failure: (1) PS
, with an inspiratory support ≥8 cmH
O; (2) NAVA, adjusting the NAVA level to achieve a comparable peak EAdi (EAdi
) as during PS
; and (3) PS
, setting the NAVA level at 15 cmH
O/μV with an upper airway pressure (Paw) limit to obtain the same overall Paw applied during PS
. We assessed patient comfort, peak inspiratory flow (PIF), time to reach PIF (PIF
), EAdi
, arterial blood gases, pressure-time product of the first 300 ms (PTP
) and 500 ms (PTP
) after initiation of patient effort, inspiratory trigger delay (Delay
), and rate of asynchrony, determined as asynchrony index (AI%). The categorical variables were compared using the McNemar test, and continuous variables by the Friedman test followed by the Wilcoxon test with Bonferroni correction for multiple comparisons (p < 0.017).
PS
significantly improved patient comfort, compared to both PS
(p = 0.001) and NAVA (p = 0.002), without differences between the two latter (p = 0.08). PIF (p = 0.109), EAdi
(p = 0.931) and gas exchange were similar between modes. Compared to PS
and NAVA, PS
reduced PIF
(p < 0.001), and increased PTP
(p = 0.004) and PTP
(p = 0.001). NAVA and PS
significantly reduced Delay
, as opposed to PS
(p < 0.001). During both NAVA and PS
, AI% was <10% in all patients, while AI% was ≥10% in 7 patients (50%) with PS
(p = 0.023 compared with both NAVA and PS
).
Compared to both PS
and NAVA, PS
improved comfort and patient-ventilator interaction during NIV by facial mask. PS
also improved synchrony, as opposed to PS
only.
ClinicalTrials.gov, NCT03041402 . Registered (retrospectively) on 2 February 2017.
Population health and well-being in Latin America, the current epicenter of the COVID-19 pandemic, has been severely affected during the past semester. Despite the growing evidence about the link ...between the pandemic, its control measures, and mental health worldwide, there is still no regional evidence of the potential mental health impact. We describe the prevalence and distribution of depressive symptoms across demographic and socioeconomic risk factors in the Peruvian population amidst a national lockdown during the COVID-19 pandemic.
Cross-sectional study conducted during the community transmission phase and national lockdown in Peru (May 4th-16th, 2020). We recorded 64,493 responses from adult Peruvian residents through an opt-in online questionnaire. All analyses were weighted using raking based on proportions of sociodemographic variables from the last Peruvian census in 2017. The prevalence of depressive symptoms was calculated using the Patient Health Questionnaire (PHQ-9) score of 10 or more. We identified associated demographic and socioeconomic factors by prior mental health diagnosis. Sensitivity analysis considered an alternative cut-off point for depressive symptoms of PHQ-9 ≥ 14.
A total of 57,446 participants were included in the analytical sample. A third of the participants (n = 23,526, unweighted) showed depressive symptoms in the 2 weeks prior to the study. Participants who reported a previous mental health diagnosis doubled the sample prevalence of depressive symptoms (59, 95%CI 56.7, 61.4%) of those without a prior diagnosis. Psychosocial and functioning reactions were largely more prevalent among females and young adults. A dose-response relationship was found between household income and depressive symptoms across previous mental health diagnosis strata, being as low as 32% less in the wealthiest than the most impoverished group (PR: 0.68, 95%CI 0.58,0.79). Other critical factors associated with a higher burden of depressive symptoms were lower education level, single, unemployed, and chronic comorbidity.
An increased burden of depressive symptoms and psychosocial reactions has emerged during the COVID-19 pandemic in Peru compared to previous years. The mental health burden disproportionately affects women, the younger population, and those with low income and education. As the country eases the social distancing measures, it is crucial to use local evidence to adjust public health policies and mental health services to the renewed population needs.
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Despite an apparent effective vaccination, some patients are admitted to the hospital after SARS-CoV-2 infection. The role of adaptive immunity in COVID-19 is growing; nonetheless, differences in the ...spike-specific immune responses between patients requiring or not hospitalization for SARS-CoV-2 infection remains to be evaluated. In this study, we aim to evaluate the spike-specific immune response in patients with mild-moderate or severeSARS-CoV-2 infection, after breakthrough infection following two doses of BNT162b2 mRNA vaccine.
We included three cohorts of 15 cases which received the two BNT162b2 vaccine doses in previous 4 to 7 months: 1) patients with severe COVID-19; 2) patients with mild-moderate COVID-19 and 3) vaccinated individuals with a negative SARS-CoV-2 molecular pharyngeal swab (healthy subjects). Anti-S1 and anti-S2 specific SARS-CoV-2 IgM and IgG titers were measured through a chemiluminescence immunoassay technology. In addition, the frequencies of IFNγ-releasing cells were measured by ELISpot.
The spike-specific IFNγ-releasing cells were significantly lower in severe patients (8 0; 26 s.f.c.×106), as compared to mild-moderate patients (135 64; 159 s.f.c.×106; p<0.001) and healthy subjects (103 50; 188 s.f.c.×106; p<0.001). The anti-Spike protein IgG levels were similar among the three cohorts of cases (p = 0.098). All cases had an IgM titer below the analytic sensitivity of the test. The Receiver Operating Curve analysis indicated the rate of spike-specific IFNγ-releasing cells can discriminate correctly severe COVID-19 and mild-moderate patients (AUC: 0.9289; 95%CI: 0.8376-1.000; p< 0.0001), with a diagnostic specificity of 100% for s.f.c. > 81.2 x 106.
2-doses vaccinated patients requiring hospitalization for severe COVID-19 show a cellular-mediated immune response lower than mild-moderate or healthy subjects, despite similar antibody titers.
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