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.

Determinants of incorrect inhaler technique in chronic obstructive pulmonary disease patients.

AIMS: There is a lack of an overview of determinants of incorrect inhaler technique among chronic obstructive pulmonary diseases (COPD) subjects. The aim of this study was to determine the prevalence and possible determinants of incorrect inhaler technique in COPD subjects with common inhalers. METHODS: A cross over study was conducted in 180 COPD subjects. Baseline assessment of inhaler technique was evaluated in 10 placebo inhalers including: [pressurised metered dose inhaler (pMDI), Aerolizer, Handihaler, Turbohaler, Discus, Breezhaler, Ellipta, Easyhaler, Diskhaler and Respimat] without receiving any instructions. Subjects were then crossed over to other inhalers in random order. Inhaler technique was assessed. The proper technique of inhalers was demonstrated and the number of counselling attempts needed to achieve a correct technique was recorded. Patient past-experience, demographics/clinical variables were recorded. RESULTS: Incorrect inhaler techniques were highly prevalent among COPD subjects, ranging from 80% of participants demonstrated incorrect use, a minimum of 1 error, with Ellipta, to 100% with Respimat/Diskhaler (P < .001). Past-experience (OR = 14.639 at P < .001) and inhaler-type (OR = 10.397 at P < .001, 4.267 at P =. 007, 2.664 at P =. 057, 8.666 at P =. 001, 10.250 at P < .001, 0.613 at P =. 212 and 0.265 at P< .001 for pMDI, Aerolizer, Handihaler, Turbohaler, Discus, Breezhaler and Ellipta, respectively) were the strongest determinants of incorrect technique followed by gender (OR = 0.310 at P < .001), age category (OR = 0.307 at P < .001) and GOLD group (OR = 2.289 at P =. 005). CONCLUSION: Incorrect inhaler techniques are highly prevalent among COPD subjects. Lack of past-experience, certain inhaler types, female gender, older age and lower GOLD group are the most significant determinants of incorrect technique.

Real-life assessment of chronic obstructive pulmonary disease patient performance with different inhalers.

PURPOSE: This study aimed to evaluate handling of six common inhalers and to determine correlations between correct inhaler technique and patient demographics/ clinical variables. METHODS: A total of 180 chronic obstructive pulmonary disease (COPD) patients were crossed-over to handle their past-experienced inhalers among (pMDI, Aerolizer, Handihaler, Breezhaler, Turbohaler, and Diskus) randomly, without receiving verbal or demonstrative instruction (baseline assessment). Inhaler technique was assessed using previously defined checklists. The correct use of the inhaler was then demonstrated and the patient was evaluated for inhaler use again. Demonstration was repeated until a correct technique was achieved. Number of counselling attempts needed to a complete right handling, patient demographics and clinical variables were recorded. RESULTS: The mean percentage of total correct steps showed that pMDI is significantly lower than all other inhalers (76.01 ± 12.61 vs 84.18 ± 10.87, 84.60 ± 12.10, 85.91 ± 9.82, 90.63 ± 9.29 and 91 ± 10.22 for Diskus, Turbohaler, Aerolizer, Handihaler and Breezhaler, respectively, at P < .001). Breezhaler showed the lowest percentage of participants with at least 1 critical error (20%) however, pMDI showed the highest percentage (85.19%) at P < .05. Breezhaler showed that the highest percentage of participants achieved a complete right handling after 1st counselling attempt, however, pMDI was the only inhaler included in a 3rd and 4th counselling attempts (5.93% and 0.74%, respectively). Weak and very weak correlations were found between total correct steps and demographics/clinical variables. CONCLUSIONS: pMDI is not preferable for handling by COPD patients. DPIs vary in ease of use, so that inhaler therapy must be individualised on basis of patient handling assessment with repeated counselling.

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.

First-time handling of different inhalers by chronic obstructive lung disease patients.

Background: There is a lack of guidance on inhaler device selection and how to individualize inhaler choice when prescribed for the first-time.Aim of the work: To compare different inhalers regarding ease of use and number of counseling attempts needed for correct handling in subjects with a first experience to such inhalers; also, to investigate if there is a correlation between total correct steps achievements and patient demographics/clinical variables.Method: An open-label, non-drug interventional, cross-over study was conducted including 180 Egyptian patients with chronic obstructive pulmonary disease (COPD). The study evaluated handling of the most common inhalers in subjects with a first experience with them before hospital discharge. Subjects were randomized to handle 10 placebo inhalers including: [metered dose inhaler (pMDI), Aerolizer, Handihaler, Turbohaler, Diskus, Breezhaler, Ellipta, Easyhaler, Diskhaler, and Respimat] without receiving verbal or demonstrative instruction with allowable access to the patient information leaflets in native language supported by figures with enough time to read (baseline assessment). Subjects were then crossed-over to other inhalers with a first experience randomly. Inhalers with a reported past-experience were excluded. Inhaler-technique was assessed by using previously defined checklists, including essential steps and critical errors. The whole handling of the inhaler was demonstrated and the number of counseling attempts needed to correct handling was recorded. Patient demographics and clinical variables were recorded and correlated with correct handling steps.Results: The baseline percentages of total correct steps achievements as mean ± SD were 50 ± 19, 52 ± 16, 58 ± 14, 60 ± 17, 64 ± 10, 67 ± 16, 72 ± 17, 73 ± 11, 77 ± 14 and 86 ± 11% for Respimat, pMDI, Diskhaler, Diskus, Aerolizer, Handihaler, Easyhaler, Turbohaler, Breezhaler, and Ellipta respectively with p < 0.001. Baseline percentages of participants with at least 1 critical error significantly differed between inhalers (p < 0.05) with Ellipta showing the lowest percentage (37%). pMDI, Diskhaler, and Respimat showed the highest percentages (100%, 97% and 94% respectively). The number of counseling attempts needed to reach correct handling showed a significant difference among inhalers (p < 0.05). Ellipta showed the highest percentage of participants with correct handling with no counseling (20%) and the highest percentage of participants achieved with one counseling attempt (78%). Diskhaler, pMDI, and Respimat were the only inhalers included in a fourth counseling attempt (15%, 9%, and 6% respectively). Weak and very weak correlations were found between patient demographics/clinical variables and percentages of total correct steps achievements.Conclusion: Inhalers techniques greatly vary in their ease of use (self-explaining) ranging from easy inhalers (Ellipta) to intermediate inhalers (breezhaler, Easyhaler, Turbohaler, Aerolizer, Handihaler, and Diskus) followed by the most difficult inhalers (pMDI, Diskhaler, and Respimat). That must be considered when prescribing inhalers for the first time; choice of the inhaler should, in part, be based on ease of use and to be accompanied by repeated counseling.

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.

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.

High-Flow Nasal Oxygen Therapy in Acute Hypoxemic Respiratory Failure: Concise Review on Technology and Initial Methodology.

High-flow nasal cannula oxygen therapy (HFNCOT) system consists of an air/oxygen supply system capable of delivering up to 100% humidified and heated oxygen at a flow rate of up to 80 L/min. The system includes a blender, active humidifier, single heated tube, and nasal cannula. HFNCOT has many physiological advantages compared with other standard oxygen therapies, such as anatomical dead space washout, more constant fraction of inspired oxygen, positive end-expiratory (PEEP) effect, supplement of adequate humidification and maintenance of muco-ciliary function. HFNCOT is mostly used for hypoxemic acute respiratory failure, although it also has other indications. HFNCOT is a common choice of physicians as its technology makes it more silent and comfortable. Though HFNCOT is used in many clinical settings, there is a lack of publications addressing devices and initial settings. We present a review on HFNCOT, with focus on device and application methodology.

Prevalence and predictors of suboptimal peak inspiratory flow rate in COPD patients.

The aim of this study was to determine prevalence and possible clinical predictors of suboptimal peak inspiratory flow rate (PIFR) with different dry powder inhalers. PIFR was measured across all resistance ranges of In-Check Dial® in 180 chronic obstructive pulmonary disease (COPD) subjects before hospital discharge. COPD subjects were defined as suboptimal if measured PIFR was suboptimal with any resistance representative of specific inhalers (R1-R5). Demographics and clinical data were collected, including COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) scores, Global Initiative for Obstructive Lung Disease (GOLD) stage spirometry by Spirodoc® and peak flow meter measurements with portable peak inspiratory and expiratory flow meters. All were correlated with In-Check Dial PIFRs. Suboptimal PIFR was 44.44% prevalent in COPD subjects. 55% of the suboptimal cohort was female which represent 57.14% of the total female population in the study. The distribution of suboptimal PIFR included 43.75% with R1, 67.5% with R2, 100% with R3, 13.75% with R4, and 21.25% with R5. In the suboptimal cohort, CAT score was significantly higher and spirometry demonstrated significantly lower lung function results compared to the optimal cohort (p < 0.05). The only parameter to show strong and moderate correlation with In-Check Dial PIFRs was PIFR measured by peak flow meter (p < 0.001). Suboptimal PIFR is common among COPD subjects at hospital discharge. Female gender and peak flow meter PIFR was the only predictor of suboptimal PIFR. Inhaler therapy for COPD patients must be personalized based on simple routine measurement of In-Check Dial PIFRs or peak flow meter PIFR to optimize clinical benefits .