Performance of newly developed add-on devices on aerosol delivery in noninvasive ventilated subjects.

Background: Several techniques had been developed to generate aerosolized medications during noninvasive ventilation (NIV) using variable inhalation methods. This study hypothesized that large spacers were more efficient significantly than small spacers and adapters during NIV. Objective: The main objective of this study was to compare the performance of newly developed spacers with standard T-piece in NIV chronic obstructive pulmonary disease (COPD) subjects. Methods: Sixty COPD subjects requiring NIV were included in this study. A dual-limb circuit was used, and the mode of ventilator was set in spontaneous volume-controlled mode. Dual-limb ventilation circuit, consists of inspiratory-limb and expiratory-limb, is pressure and volume controlled in response to subject expiration providing relatively high resistance to expiratory flow. Two experimental sets were evaluated: the first was introducing two preliminary pressurized metered-dose inhalers (pMDI) puffs before the nebulization of 1 ml of a respirable solution of salbutamol by vibrating mesh nebulizer (VMN) using Minimhal and Combihaler. The second was to only nebulize 1 ml of salbutamol respirable solution by VMN using Combihaler, Minimhal, and standard T-piece. Two urine samples were collected after aerosol delivery: urine sample after 30 min. (USAL0.5) as an indicator of lung deposition and all urine pooled 24 h (USAL24) post-inhalation as an indicator of systemic absorption. The amount of salbutamol extracted from urine samples was assayed by high-performance liquid chromatography. Results: Minimhal + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Minimhal + VMN (p < 0.001). Also, Combihaler + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Combihaler + VMN (p < 0.001). Combihaler + VMN delivered a higher percentage of salbutamol 30 min and 24 h post-inhalation than both Minimhal + VMN and T-piece + VMN (p < 0.001). Standard T-piece delivered the lowest aerosol amount delivered to the lung compared to both spacers (p < 0.05). Conclusions: Introducing two pMDI puffs significantly improved aerosol delivery by both spacers. Combihaler significantly improves aerosol delivery more than Minimhal.

Maternal and Fetal Outcome of COVID-19 Infection among Pregnant Women.

Background and Objectives: Pregnant women face an increased risk of experiencing negative consequences due to COVID-19 infection. Our study aimed to identify outcomes for both mothers and fetuses associated with COVID-19 during each trimester, as well as to identify post-COVID symptoms in this population. Materials and Methods: Among the total population, 14 females were infected during the first trimester, 25 during the second, and 66 during the third trimester. Weekly follow-ups were conducted until delivery. Seventy-five females (71.4%; 95% CI:26.9-115.9%) were admitted to the hospital secondary to COVID-19 infection. Maternal hospitalization was independently associated with COVID-19 severity (adjusted odds ratio (aOR) = 3.9; 95% CI: 1.6-9.2 at p = 0.002 relative to the reference group (mild infection)) and the presence of dyspnea at initial assessment (aOR = 6.9; 95% CI: 1.7-28.2 at p = 0.007 relative to nondyspneic patients). Results: The duration of hospitalization (mean ± SD) was higher in the third trimester than the first and second trimesters (10.1 ± 0.8 vs. 4.0 ± 1.2 days and 10.1 ± 0.8 vs. 6.2 ± 1.4 days, respectively, at p < 0.05). The number of maternal deaths in the third trimester was higher than in the first and second trimesters (16 (24.2%) vs. no deaths and 16 (24.2%) vs. 1 (4%) deaths, respectively, at p < 0.05). In terms of fetal outcomes, a good fetal condition was more likely if the mother was infected during the first trimester (92.9%) than the second (80%) or third trimesters (66.7%), but the difference was not significant. The percentage of preterm deliveries was insignificantly higher in the second trimester (16%) than the first (7.1%) and third (4.5%) trimesters. Conclusions: The most common post-COVID symptoms included persistent loss of smell, dry eyes, post-partum depression, knee pain, and myalgia. Post-COVID symptoms were more prevalent in patients infected during the third trimester. The adverse outcomes of COVID-19 infection for both mother and fetus were more severe in cases where the infection occurred during the third trimester compared to the second and first trimesters. Therefore, it is crucial to adhere to precautionary measures against COVID-19, prioritize vaccination, and provide comprehensive care for pregnant mothers.

Impact of n-3 polyunsaturated fatty acid intake in pregnancy on maternal health and birth outcomes: systematic review and meta-analysis from randomized controlled trails.

BACKGROUND: Maternal omega-3 consumption during pregnancy has been positively linked with a positive impact on maternal health and fetal growth. However, the results of individual studies are inconsistent and conflicting. OBJECTIVE: Examine the effect of supplementation with DHA, and/or EPA, and/or ALA throughout pregnancy on offspring's growth and pregnancy outcomes. DESIGN: A systematic review and meta-analysis. POPULATION: Pregnant women. METHODS: According to (PRISMA) statement and the Cochrane Handbook guidelines. Human trials (RCT or quasi-RCT) which involved oral omega-3 supplementation at least twice a week during pregnancy were included and comparing it with control groups with no supplementation or placebo administration. Data were extracted and directed using RevMan software. Fifty-nine randomized controlled trials were eligible for inclusion in the meta-analysis. Performed in MEDLINE, PubMed, Scopus, Google Scholar, and the Cochrane Library comparing omega 3 with control groups, from 1990 to 2020. THE MAIN OUTCOME MEASURES: The primary outcome measures were pregnancy-induced hypertension, preeclampsia, gestational duration, preterm birth, early preterm birth, birth weight, low birth weight, neonatal length, and head circumference. The secondary outcomes were neonatal intensive care unit, infant death, prenatal death, and cesarean section. RESULTS: In 24 comparisons (21,919 women) n-3 fatty acids played a protective role against the risk of preeclampsia (RR = 0.84, 95% CI 0.74-0.96 p = 0.008; I2 = 24%). In 46 comparisons (16,254 women) n-3 fatty acids were associated with a significantly greater duration of pregnancy (MD = 1.35, 95% CI 0.65-2.05, p = 0.0002; I2 = 59%). 27 comparisons (15,510 women) was accompanied by a significant decrease in pre-term birth less than 37 weeks (RR = 0.86, 95% CI 0.77-0.95, p = 0.005; I2 = 0%). 12 comparisons (11,774 women) was accompanied by a significant decrease in early pre-term birth less than 34 weeks (RR = 0.77, 95% CI 0.63-0.95, p = 0.01; I2 = 40%). 38 comparisons (16,505 infants) had a significant increase in birth weight (MD = 49.19, 95% CI 28.47-69.91, p < 0.00001; I2 = 100%). Finally, 14 comparisons (8,449 infants) had a borderline significance in increase in low birth weight (RR = 0.88, 95% CI 0.78-1.00, p = 0.05; I2 = 28%). CONCLUSIONS: Supplementation with omega-3 in prgnancy can prevent preeclampsia, increase gestational duration, increase birth weight and decrease the risk of low birth weight and preterm birth.

Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.

Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients.

Objectives: This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. Method: COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose.Results: The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(p < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (p < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (p < 0.001).Conclusion: Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.

Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations.

Aim: This systematic review aimed to investigate the drugs used and their potential effect on noninvasive ventilation (NIV). Background: NIV is used increasingly in acute respiratory failure (ARF). Sedation and analgesia are potentially beneficial in NIV, but they can have a deleterious impact. Proper guidelines to specifically address this issue and the recommendations for or against it are scarce in the literature. In the most recent guidelines published in 2017 by the European Respiratory Society/American Thoracic Society (ERS/ATS) relating to NIV use in patients having ARF, the well-defined recommendation on the selective use of sedation and analgesia is missing. Nevertheless, some national guidelines suggested using sedation for agitation. Methods: Electronic databases (PubMed/Medline, Google Scholar, and Cochrane library) from January 1999 to December 2019 were searched systematically for research articles related to sedation and analgosedation in NIV. A brief review of the existing literature related to sedation and analgesia was also done. Review results: Sixteen articles (five randomized trials) were analyzed. Other trials, guidelines, and reviews published over the last two decades were also discussed. The present review analysis suggests dexmedetomidine as the emerging sedative agent of choice based on the most recent trials because of better efficacy with an improved and predictable cardiorespiratory profile. Conclusion: Current evidence suggests that sedation has a potentially beneficial role in patients at risk of NIV failure due to interface intolerance, anxiety, and pain. However, more randomized controlled trials are needed to comment on this issue and formulate strong evidence-based recommendations. How to cite this article: Karim HMR, Sarc I, Calandra C, Spadaro S, Mina B, Ciobanu LD, et al. Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations. Indian J Crit Care Med 2022;26(8):938-948.

Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID-19 patients treated with tocilizumab.

BACKGROUND: The treatment of severe cases of COVID-19 disease remains a dilemma so far, because there is no approved therapy for it. This study aimed to estimate the therapeutic efficacy of tocilizumab and its role in reducing the need for mechanical ventilation, length of hospital stay, mortality rate for these cases. METHOD: The study included 25 adult patients with confirmed severe COVID-19 infection. Treatment of all patients followed Egyptian Ministry of Health COVID-19 protocol in addition to tocilizumab IV (400-800 mg) as a single dose and then the dose was repeated after at least 12 hours and up to 24 hours from the previous dose. All laboratory and clinical parameters were assessed before and within 24 hours after tocilizumab administration. RESULTS: After receiving TCZ, all patients showed significantly lower median IL 6, LDH, CRP, ferritin , TLC at P < .001, and D-Dimer at P = .223 than their baseline levels. Also, the number of patients who required mechanical ventilation decreased from 11 to 8. Only five patients died after TCZ treatment. A moderate correlation was found between therapeutic failure and death outcomes and mechanical ventilation need at baseline. The median days of hospitalisation (IQR) were 10 (6-16). CONCLUSION: Tocilizumab treatment in patients with severe COVID-19 is safe and has significant therapeutic effects and a significant role in the improvement of all laboratory parameters. Also TCZ plays a significant role in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation, and mortality rate.What's known IL-6 plays the main role in the acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infection. Consequently, serum IL-6 can be considered as an important target in therapeutic management of severe COVID-19 patients. What's new Prospective study, carried on 25 adult patients with confirmed severe COVID-19 infection using tocilizumab, showed significant improvement in their case. Tocilizumab, as an IL-6 inhibitor, not only lowered IL-6 level put also showed a significant reduction on median LDH, CRP, ferritin , TLC at P < .001 and D-Dimer at P = .223 than their baseline levels. Improvement of all laboratory parameters using TCZ was reflected in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation and mortality rate.

The impact of changing patient interfaces on delivering aerosol with titrated oxygen in the high flow system.

INTRODUCTION: Despite the widespread oxygen-culture as more is better in prehospital and hospital settings, the use of titrated oxygen-flow within a high-flow system can be beneficial especially when combined with aerosol-delivery and also save the patient from unnecessary-hyperoxia. METHODS: Forty-five COPD patients were included in this study where they allocated in three-groups (nasal-delivery, oral-delivery, and oronasal-delivery groups). All patients were received their inhaled-salbutamol dose using Aerogen Solo nebuliser by one of the three interfaces, eg, nasal-cannula, mouthpiece, and facemask in two conditions; with oxygen-flow and without any oxygen-flow. Pulmonary and systemic salbutamol deposition was estimated by collecting two urine-samples from the patient; 30 min post-inhalation and cumulatively 24 hr post-inhalation. The quantity of salbutamol in these collected samples was measured by high-performance liquid chromatography. Lung function measurement was performed pre-bronchodilator inhalation and 30 min post-bronchodilator to estimate the change in pulmonary functions post-inhalation regarding all tested interfaces. RESULTS: COPD patients showed the highest salbutamol percentage excreted 30 min post-inhalation of 5.7% (1.4) with mouthpiece interface when combined with oxygen at P < .002. While with the same condition using oxygen, valved-facemask showed the highest salbutamol percentage excreted in 24 hr post inhalation samples but the difference is only significantly compared with nasal cannula (P < .006). Moreover, without oxygen delivery, mouthpiece and valved facemask showed approximately the same salbutamol percentage excreted in 30 min post-inhalation samples, higher than that delivered by nasal cannula (P < .001). Of note, salbutamol delivery is significantly increased with oxygen flow for all interfaces (P < .05) except with nasal cannula. CONCLUSIONS: The nasal cannula is a more comfortable and tolerable interface despite the lower fraction of the delivered drug compared with other tested interfaces. The use of oxygen-flow with aerosol delivery within a high flow system positively affects the delivered drug fraction and the pulmonary deposition of the drug.

Aerosol drug-delivery and short-term clinical outcomes of suboptimal peak inspiratory flow rate in chronic obstructive pulmonary disease.

AIM OF WORK: Suboptimal peak inspiratory flow rate (PIFR) is highly prevalent in chronic obstructive pulmonary disease (COPD) patients owing to the mismatch of their own PIFR with the corresponding inhaler-device resistance. This study aimed to evaluate aerosol drug-delivery and short-term clinical outcomes of suboptimal PIFR in COPD subjects. METHODS: Twenty optimal and suboptimal COPD subjects were crossed over in this prospective, randomised, controlled, open-label study. They were tested for urinary salbutamol amount (USAL30) and spirometric response 30 min poststudy dose (200 µg salbutamol) through Aerolizer® and Handihaler® after assessment of their own PIFR through In-Check™ Dial G16. Urine samples were extracted through solid-phase extraction and assayed through a high performance liquid chromatography (HPLC) method. RESULTS: Mean USAL30 was significantly higher in the optimal group than in the suboptimal group (P = .001). There was no significant difference in ΔFEV1% predicted and ΔFVC% predicted between optimal and suboptimal groups, with higher values in optimal Aerolizer® and Handihaler® than in suboptimal groups. CONCLUSION: Suboptimal PIFR was associated with a significantly lower drug delivery in COPD subjects at hospital discharge, and a slightly lower pulmonary function response 30 min postbronchodilation if compared with optimal PIFR.

Effect of verbal counselling on metred-dose inhaler proper use and lung function test amongst asthmatic patients: A meta-analysis.

INTRODUCTION: The main cause of poor asthma control is mostly related to the inability of the asthmatic subjects to use their metred-dose inhaler (pMDI) correctly. The present study aimed to evaluate the role of contentious pMDI verbal-counselling on the pMDI inhalation technique and pulmonary functions of asthmatics. METHODS: Through a systematic literature search up to December 2020, 10 studies with 1937 asthmatic subjects, who had at least two pMDI inhalation technique verbal counselling sessions (visits), were identified reporting relationships between contentious pMDI verbal counselling, and the number of inhalation technique mistakes and lung functions score. Mean difference (MD) with 95% confidence intervals (CIs) was calculated comparing counselling visits results using the continuous method with a random effect model. RESULTS: Visit 1 had a significantly higher mean number of mistakes compared with visit 2 (MD, 19.98; 95% CI, 11.54-28.41, P < .001); Also, visit 2 had a significantly higher mean number of mistakes compared with visit 3 (MD, 12.17; 95% CI, 9.31-15.02, P < .001). The extent of improvement in the inhalation technique was higher between visits 1 and 2 compared with that between visits 2 and 3. The impact of continuous verbal counselling was also observed on the forced expiratory volume in one second as percentage of vital capacity [(MD, -5.56; 95% CI, -6.50 to -4.61, P < .001) between visits 1 and 2 and (MD, -6.40; 95% CI, -7.71 to -5.10, P < .001) between visits 2 and 3] and the peak expiratory flow rate [(MD, -11.47; 95% CI, -18.73 to -4.22, P < .001) between visits 1 and 2 and (MD, -16.53; 95% CI, -25.80 to -7.26, P < .001) between visits 2 and 3]. The extent of improvement in lung functions was similar between visits 1 and 2 and visits 2 and 3. CONCLUSION: Based on this meta-analysis, Continuous pMDI verbal counselling, at every possible opportunity, is a must since lung functions and pMDI inhalation technique improvements were observed with continuous pMDI verbal counselling.

Coffee and type 2 diabetes risk: Is the association mediated by adiponectin, leptin, c-reactive protein or Interleukin-6? A systematic review and meta-analysis.

AIM: Coffee and diabetes risk association has been demonstrated in numerous studies; however, the exact mechanism has not been clarified yet. The present meta-analysis was conducted to cover the current knowledge regarding the effect of coffee on Type 2 Diabetes (T2D), in addition to the evaluation of adiponectin, leptin, C-reactive protein (CRP) and Interleukin-6 (IL-6) levels among coffee consumers as relatively possible mediators of this effect. METHOD: A comprehensive search of the literature was carried out using search engines up to March 2020. The effect sizes were investigated using the standardised mean difference (SMD) and odds ratios (OR) or relative risk (RR) with its 95% confidence interval (CI). A total of 69 cross-sectional and cohort studies were included and divided as follows: 31 articles for T2D risk, 15 studies for adiponectin, 6 studies for leptin, 12 studies for CRP and 5 studies for IL-6. RESULTS: Overall, coffee consumption was inversely associated with T2D risk with an estimated pooled RR of 0.73 (95% confidence interval [0.68, 0.80] for the highest vs lowest coffee consumption categories. The combined SMD between the different coffee intake categories, showed that coffee consumption was associated with higher adiponectin levels (P = .002), and lower level of leptin (P = .04) and CRP (P = .2), with apparently no change in IL-6 levels (P = .91). CONCLUSION: The present meta-analysis showed strong epidemiological evidence that coffee consumption is inversely associated with the risk of T2D. Also, adiponectin, leptin concentrations appeared to be potential mediators of the coffee effect on diabetes, while IL-6 levels did not.

COVID-19; current situation and recommended interventions.

BACKGROUND: The new coronavirus (SARS-COV-2) that emerged at the end of 2019 was stated in China and infected millions of people around the world, with the highest spread rate amongst humans compared with other coronaviruses. This paper aimed to review and analyse the published studies about COVID-19 diagnosis, prevention, and treatment. METHOD: The reviewed studies were clinical trials, in-vivo, in-vitro, guidelines, reports from the world health organization (WHO), and the centre for disease control and prevention (CDC) in addition to systemic reviews. All data extracted and analysed to stand on the latest updates and recommendations for fighting this severe attack of COVID-19. RESULTS: Most important antiviral therapy of COVID-19 clinical trials is still running without clear results, but a few trials have indicated the role of numerous drugs in the treatment of COVID-19. Specific recommendations for aerosol therapy should be followed for the management of COVID-19. CONCLUSION: Nature of COVID-19 is still not very clear, however, management of the condition is similar to the previous attacks of coronaviruses.

A study of the possible factors affecting COVID-19 spread, severity and mortality and the effect of social distancing on these factors: Machine learning forecasting model.

BACKGROUNDS: SARS-CoV-2 is affecting different countries all over the world, with significant variation in infection-rate and death-ratio. We have previously shown a presence of a possible relationship between different variables including the Bacillus Calmette-Guérin (BCG) vaccine, average age, gender, and malaria treatment, and the rate of spread, severity and mortality of COVID-19 disease. This paper focuses on developing machine learning models for this relationship. METHODS: We have used real-datasets collected from the Johns Hopkins University Center for Systems Science and Engineering and the European Centre for Disease Prevention and Control to develop a model from China data as the baseline country. From this model, we predicted and forecasted different countries' daily confirmed-cases and daily death-cases and examined if there was any possible effect of the variables mentioned above. RESULTS: The model was trained based on China data as a baseline model for daily confirmed-cases and daily death-cases. This machine learning application succeeded in modelling and forecasting daily confirmed-cases and daily death-cases. The modelling and forecasting of viral spread resulted in four different regions; these regions were dependent on the malarial treatments, BCG vaccination, weather conditions, and average age. However, the lack of social distancing resulted in variation in the effect of these factors, for example, double-humped spread and mortality cases curves and sudden increases in the spread and mortality cases in different countries. The process of machine learning for time-series prediction and forecasting, especially in the pandemic COVID-19 domain, proved usefulness in modelling and forecasting the end status of the virus spreading based on specific regional and health support variables. CONCLUSION: From the experimental results, we confirm that COVID-19 has a very low spread in the African countries with all the four variables (average young age, hot weather, BCG vaccine and malaria treatment); a very high spread in European countries and the USA with no variable (old people, cold weather, no BCG vaccine and no malaria). The effect of the variables could be on the spread or the severity to the extent that the infected subject might not have symptoms or the case is mild and can be missed as a confirmed-case. Social distancing decreases the effect of these factors.

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees.

INTRODUCTION: Aerosol delivery from DPIs could be affected by different factors. This study aimed to evaluate and predict the effects of different factors on drug delivery from DPIs. METHODS: Modelling and optimisation for both in vitro and in vivo data of different DPIs (Diskus, Turbohaler and Aerolizer) were carried out using neural networks associated with genetic algorithms and the results are confirmed using a decision tree (DT) and random forest regressor (RFR). All variables (the type of DPI, inhalation flow, inhalation volume, number of inhalations and type of subject) were coded as numbers before using them in the modelling study. RESULTS: The analysis of the in vitro model showed that Turbohaler had the highest emitted dose compared with the Diskus and the Aerolizer. Increasing flow resulted in a gradual increase in the emitted dose. Little differences between the inhalation volumes 2 and 4 litres were shown at fast inhalation flow, and interestingly two inhalations showed somewhat higher emitted doses than one-inhalation mode with Turbohaler and Diskus at slow inhalation flow. Regarding the in vivo model, the percent of drug delivered to the lung was highly increased with Turbohaler and Diskus in healthy subjects where continuous contour lines were observed. The Turbohaler showed increased lung bioavailability with the two-inhalation modes, the Diskus showed a nearly constant level at both one and two inhalations at slow inhalation. The Turbohaler and Aerolizer showed little increasing effect moving from one to two inhalations at slow inhalation. CONCLUSIONS: Modelling of the input data showed a good differentiating and prediction power for both in vitro and in vivo models. The results of the modelling refer to the high efficacy of Diskus followed by Turbohaler for delivering aerosol. With two inhalations, the three DPIs showed an increase in the percent of drug excreted at slow inhalations.

Impact of Preliminary Bronchodilator Dose in Chronic Obstructive Pulmonary Disease Patients With Suboptimal Peak Inspiratory Flow.

PURPOSE: Suboptimal peak inspiratory flow rate (PIFR) is highly prevalent in patients with chronic obstructive pulmonary disease (COPD) owing to the mismatch of their PIFR with the corresponding inhaler-device resistance. This study aimed to investigate the impact of a preliminary dose of pressurized metered dose inhalers (pMDIs) on patients with COPD with suboptimal PIFR using Diskus dry powder inhalers (DPIs). METHODS: A prospective, randomized, case-control study included 24 patients with COPD. PIFR was measured using the In-Check Dial G16 with low-to-medium resistance. Spirodoc was used to measure baseline spirometric data and compare it before and 30 minutes after the administration of Diskus DPI. On a different day, the study dose was given to each suboptimal patient by the same aerosol generator with preceded 2 puffs of salbutamol pMDI and re-evaluated for spirometric parameters 30 minutes after the study dose. FINDINGS: There was a significant difference between the optimal and suboptimal groups in peak expiratory flow (2.38 ± 1.20 vs 1.49 ± 1.06 L/s, P = 0.050). PIFR showed a statistically significant difference between the optimal and suboptimal groups (71.66 ± 6.15 vs 41.25 ± 9.79 L/min, P < 0.0001). There was a significant difference in forced vital capacity (ΔFVC) between optimal and suboptimal groups without a preliminary dose (0.42 ± 0.21 vs 0.16 ± 0.11 L, P = 0.002), forced expiratory volume in 6 seconds (ΔFEV6) (0.53 ± 0.49 vs 0.17 ± 0.11 L, P = 0.022), forced expiratory volume in 3 seconds (ΔFEV3) (0.41 ± 0.38 vs 0.1 ± 0.16 L, P = 0.013), forced expiratory volume in 1 second (ΔFEV1)/FVC (-2.38 ± 8.41 vs 2.96% ± 2.95%, P = 0.033), and ΔFEV1/FEV6 (-4.32 ± 11.23 vs 2.91% ± 4.35%, P = 0.015). There was a significant difference in ΔFVC between optimal and suboptimal groups with a preliminary dose (0.42 ± 0.21 vs 0.23 ± 0.18 L, P = 0.046), ΔFEV1/FVC (-2.38 ± 8.41 vs 5.67% ± 6.53%, P = 0.009), ΔFEV1/FEV6 (-4.32 ± 11.23 vs 5.16% ± 4.99%, P = 0.008), and forced expiratory time (ΔFET) (0.28 ± 0.45 vs -0.31 ± 0.70 seconds, P = 0.022). The only parameter that showed a significant difference between suboptimal groups without and with a preliminary dose is Δ peak expiratory flow (0.24 ± 0.59 vs 0.65 ± 0.68 L/s, P = 0.004). IMPLICATIONS: Administering a preliminary dose of pMDI can minimally enhance the effectiveness of DPIs in patients with COPD with suboptimal PIFR and health outcomes.

Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients.

BACKGROUND: The effectiveness of the best combination between different antiviral and anti-inflammatory drugs stills an interest in the treatment of COVID19 infection. PATIENTS AND METHODS: A prospective randomized cohort study comprised 108 adult patients with confirmed PCR COVID 19 infection with systemic hyper inflammation state, divided into two groups according to the treatment regimen, 56 in the tocilizumab- hydroxychloroquine (TCZ-HCQ) treatment, and 52 in the tocilizumab-remdesivir (TCZ-RMV) treatment. The first group received a combination of I.V. TCZ (400-800 mg every 24 h for only two doses) and HCQ (400 mg twice in the first day then 200 mg twice for 5 days) while the second group of patients received I.V. RMV of 200 mg on day 1 followed by 100 mg once daily infused over 60 min for 5 days with the same TCZ regimen used in the first group. All clinical parameters and laboratory investigations were assessed before and after treatment. RESULTS: The CRP was significantly decreased while PaO2/FiO2 (P/F) ratio post-treatment was significantly improved in both treatment groups. TCZ-HCQ group showed a significant decrease in the ferritin, LDH, and D. Dimer levels. The median days of hospitalization with interquartile range (IQR) were 10 (6-16) and 8 (5-12) for TCZ-HCQ and TCZ-RMV groups, respectively. The numbers of mechanically ventilated patients were 25 and 43 for TCZ-HCQ and TCZ-RMV groups, respectively. Therapeutic failure was about 26.8% in the TCZ-HCQ group and 30.8% in the TCZ-RMV group but there was no significant difference between both groups. Some complications were recognized only in TCZ-RMV following treatment including secondary bacterial infections (42.3%), myocarditis (15.4%), and finally pulmonary embolism (7.7%). CONCLUSION: Efficacy of both TCZ-RMV and TCZ-HCQ combinations are observed in the treatment of severe COVID-19 patients; however the increased need for ICU or mechanical ventilation in the TCZ-RMV arm contributed to the appearance of cardiac and thrombotic events. The study was registered at the Clinical Trials registry (ClinicalTrials.gov; NCT04779047).

Aerosol delivery via noninvasive ventilation: role of models and bioanalysis.

Non-invasive ventilation (NIV) is external support for respiration to assist breathing in case of respiratory failure (either hypercapnic or hypoxemic) without patient intubation. Nowadays, medicated aerosols are normally delivered to mechanically ventilated patients by nebulizers and pressurized metered-dose inhaler (pMDI) attached to adapter or spacer that fit into the ventilated circuit. Studies with obstructive lung disease patients have shown that aerosol delivery during mechanical ventilation is possible and of benefit. There are several models for investigating the aerosol delivery and deposition during mechanical ventilation such as in vitro, in vivo, and ex vivo models, these models depend on the technique used for quantitative or qualitative measurement of the deposited aerosol. In vitro models could be used for calculating the total emitted doses from different aerosol-generating devices or for aerodynamic characterization of the deposited inhaled medications. In vivo models dependents of extracting drugs from biological samples for measuring its concentration and bioavailability (pharmacokinetic model) or be dependent on the imaging technique of the radioactive aerosol. Applying different methods to predict aerosol efficiency before starting NIV and to quantify aerosol delivery during NIV are promising approaches that guide clinicians to avoid treatment failure before and during patient therapy.

Aerosol delivery aspects within a high-flow therapy system in COPD patients.

There is a lack of information about the influence of patient interfaces such as facemasks or mouthpieces on the effective dose of aerosolised drugs while using high-flow therapy in a clinical setting. These interfaces can improve pulmonary drug delivery over nasal cannulas but patient preference and comfort should also be considered. The present work was to determine the effect of three different interfaces (nasal cannula, valved face mask, and mouthpiece) when combined with titrated oxygen flow on aerosol delivery in patients with COPD hospitalised due to acute exacerbation. The variations between these interfaces were addressed in terms of change in lung function measurements pre-and post-inhalation, the delivered salbutamol dose, and patient tolerance to each interface. A high-flow nasal cannula was the most comfortable interface used. However, its pulmonary drug delivery was significantly lower than both the valved face mask and mouthpiece (p<0.05). Although drug delivery was different with the three tested interfaces, the lung function improvements were similar.

Vitamins and other immune-supportive elements as cofactors for passing the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral disease that causes a respiratory disorder, started in December of 2019 in China. Several vitamins and trace elements could help in enhancing host immunity producing antioxidant or anti-inflammatory action. This work aimed to identify the role of different nutrition, vitamins, and trace elements on the immunity status of the infected subject and the possibility of the beneficial role of these elements in the management of COVID-19. MAIN BODY: After collecting (PubMed, scholar, OVID, Embase, Cochrane Library) and investigating published articles, testing the effect of these elements on viral infection, it was found that most of these elements have a significant role during viral infection through a different mechanism, like antioxidant, anti-inflammatory, and immunomodulation. Nutritional interventions in COVID-19 infections are very important currently, and it was reported that vitamin C and D reduce the risk of acute respiratory infections. In addition, low vitamin A diets compromise the effectiveness of inactivated bovine coronavirus vaccines. Administration of N-acetyl cysteine showed a beneficial inhibitory effect in viral infections and enhanced glutathione production. The deficiency of selenium on COVID-19 subjects has a significant impact on the clinical outcome of the subjects. In addition, supplementation with vitamins proved to enhance immune response during viral infection. Vitamins and trace elements not only showed a beneficial effect but also Omega 3 fatty acids showed an immunomodulating effect during infections. SHORT CONCLUSIONS: Assessment of levels for these trace elements at the baseline and providing supplementation containing different vitamins and elements could result in better control and clinical outcomes in the case of COVID-19.