Antimicrobial prescribing in a secondary care setting during the COVID-19 pandemic.

Background: Increased antimicrobial resistance patterns lead to limited options for antimicrobial agents, affecting patient health and increasing hospital costs. Objectives: To investigate the antimicrobial prescribing patterns at two district hospitals in Northern Ireland before and during the COVID-19 pandemic. Methods: A mixed prospective-retrospective study was designed to compare pre- and during pandemic antimicrobial prescribing data in both hospitals using a Global Point Prevalence Survey. Results: Of the 591 patients surveyed in both hospitals, 43.8% were treated with 402 antimicrobials. A total of 82.8% of antimicrobial prescriptions were for empirical treatment. No significant difference existed in numbers of patients treated or antimicrobials used before and during the pandemic. There was a slight decrease of 3.3% in the compliance rate with hospital antimicrobial guidelines during the pandemic when compared with the pre-pandemic year of 2019, when it was 69.5%. Treatment based on patients' biomarker data also slightly decreased from 83.5% pre-pandemic (2019) to 81.5% during the pandemic (2021). Conclusions: There was no overall significant impact of the pandemic on the antimicrobial prescribing patterns in either hospital when compared with the pre-pandemic findings. The antimicrobial stewardship programmes would appear to have played an important role in controlling antimicrobial consumption during the pandemic.

Comparative Evaluation of Sildenafil Citrate and Estrogen as an Adjuvant Therapy for Treatment of Unexplained Infertility in Women.

BACKGROUND: Uterine blood flow determines endometrial thickness. This study examined how vaginal sildenafil citrate and estradiol valerate altered endometrial thickness, blood flow, and fertility in infertile women. METHODS: This study observed 148 infertile women whose infertility was unexplained. Group 1 comprised 48 patients who received oral estradiol valerate (Cyclo-Progynova 2 mg/12 h white tablets) from day 6 till ovulation was initiated with clomiphene citrate. A number of 50 participants in group 2 received oral sildenafil (Respatio 20 mg/12 h film-coated tablets) for 5 days starting the day after their previous menstrual period and finishing on the day they ovulated with clomiphene citrate. Group 3 was the control group, with 50 patients receiving clomiphene citrate (Technovula 50 mg/12 h tablets) ovulation induction from the 2nd to 7th day of cycle. All patients had transvaginal ultrasounds to determine ovulation, follicle count, and fertility. Miscarriage, ectopic pregnancy, and multiple pregnancies were monitored for three months. RESULTS: The three groups' mean ETs differed statistically at p = 0.0004. A statistically significant difference was found between the three groups in terms of the number of follicles, with 69% of patients in group 1 having one and 31% having two or more, 76% of patients in group 2 having one and 24% having two or more, and 90% of patients in the control group having one and 10% having two or more (p = 0.038). The clinical pregnancy rates of the three groups were 58%, 46%, and 27%, respectively (p = 0.005). The distribution of all side effects was not statistically different between the three groups. CONCLUSION: It is possible to claim that adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and, as a result, increase the pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where the infertility has lasted less than two years. Most people who take sildenafil end up with a mild headache.

Pentoxifylline Effects on Hospitalized COVID-19 Patients with Cytokine Storm Syndrome: A Randomized Clinical Trial.

COVID-19 is a fatal, fast-spreading pandemic, and numerous attempts are being made around the world to understand and manage the disease. COVID-19 patients may develop a cytokine-release syndrome, which causes serious respiratory diseases and, in many cases, death. The study examined the feasibility of employing legally available anti-inflammatory pentoxifylline (PTX), a low toxicity and cost medication, to mitigate the hyper-inflammation caused by COVID-19. Thirty adult patients who tested positive for SARS-CoV2 were hospitalized owing to the cytokine storm syndrome. They were given 400 mg of pentoxifylline orally TID according to the standard COVID-19 protocol of the Egyptian Ministry of Health. Besides this, a group of thirty-eight hospitalized COVID-19 patients who received the standard COVID-19 protocol was included in the study as a control group. The outcomes included laboratory test parameters, clinical improvements, and number of deaths in both groups. After receiving PTX, all patients showed a significant improvement in C reactive protein (CRP), and interleukin-6 (IL-6) levels at p < 0.01 and p = 0.004, respectively, while there was an increase in total leukocyte count (TLC) and neutrophil-to-leucocyte ratio (NLR) at p < 0.01 compared to their baseline levels. The D-dimer level showed a significant increase in the treatment group at p < 0.01, while showing no statistically significant difference in the control group. The median initial ALT (42 U/L) in the treatment group showed a decrease compared to the control group (51 U/L). No statistical significance was reported regarding clinical improvement, length of stay, and death percentages between the two groups. Our results showed no significant improvement of PTX over controls in clinical outcomes of hospitalized COVID-19 patients. Nevertheless, PTX displayed a positive effect on certain inflammatory biomarkers.

The impact of the clip-tone training device and its smartphone application to pressurized metered-dose inhaler in adult asthmatics.

BACKGROUND: Despite traditional inhaler technique counseling, many patients make clinically important mistakes when they use their inhalers. This study investigates the value of using a connected inhalation aid when adults with asthma use their metered-dose inhaler (pMDI). METHODS: Adult asthmatics (n = 221), using a pMDI, were randomly divided into a verbal training group (n = 110) and an enhanced training group (n = 111). 21 subjects were lost during the study, each group included 100 subjects at the end of the study. The study was divided into 3 visits. Traditional pMDI training was delivered at visit 1 to both groups which included an explanation of the steps with special stress on frequently mistaken steps e.g. exhalation before use and inhaling slowly and deeply. The enhanced training group was enhanced by using the Clip-Tone training aid linked to its dedicated smartphone app. enhanced training patients were encouraged to use this connected training aid during real-life use between the study visits. Baseline data were collected at the first visit. At all three visits (baseline, 1 month, and 2 months), subjects first completed all inhaler techniques, health outcome measures, received inhaler training, then took bronchodilators, and 30 min later repeated the lung function outcome measures. RESULTS: Both groups showed a significant decrease (p < 0.001) in the total mean number of pMDI inhalation techniques mistakes at visits 2 and 3, with a lower number of mistakes (p < 0.05) for slower inhalations for the enhanced training group compared to the verbal training group. Inhalation time (an indicator of a slow inhalation) significantly (p < 0.05) improved at each visit in the enhanced training group. In the enhanced training group, there was a gradual significant increase (p < 0.05) in lung functions while the improvements in the verbal training group were only significant (p < 0.05) at visit 3, and by visit 3, the enhanced training group had significantly higher scores than the verbal training group on both FEV1 and PEF% predicted. The asthma control test (ACT) score improved at each visit in both groups with a greater increase in the enhanced training group (p < 0.05) and more patients (44 and 21) improved their score by 3 or more in the second and third visit respectively. CONCLUSION: The connected Clip-Tone training aid helped patients improve their pMDI inhaler technique and their asthma control compared to traditional methods. These results highlight the potential of connected inhalers in the future management of inhaled therapy.

Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.

OBJECTIVES: Severe stages of COVID-19 infection have been associated with the excessive discharge of pro-inflammatory mediators such as cytokines, resulting in lung deterioration, which progresses rapidly to lung fibrosis leading to acute respiratory distress syndrome. In this investigation, the efficacy and safety of the novel antifibrotic and anti-inflammatory agent, Pirfenidone, were assessed in COVID-19 patients with pulmonary fibrosis secondary to cytokine storm. In this randomized controlled study, we assigned 100 adult COVID-19 patients cytokine storm and admitted to the intensive care isolation unit into either pirfenidone added to the standard therapy (n = 47), or the standard protocol only (n = 53). High-resolution computed tomography of the chest was performed in all patients to evaluate fibrotic lesions and their progression. The results showed that the percentage of patients who developed pulmonary fibrosis during cytokine storm onset in the pirfenidone group relative to the standard group was 29.8% and 35.8%, respectively, with no significant difference between the two groups; while there was a significant increase in the proportion of patients discharged from the isolation unit with pulmonary fibrosis without progression in fibrotic lesions in the pirfenidone group compared to the standard group (21.3% and 5.7%, respectively). Furthermore, there was a significant difference concerning liver enzyme elevation and GIT disturbance incidences in the studied groups (p = 0.006 and 0.01, respectively). Our findings show that Pirfenidone inhibits fibrosis advancement in COVID-19 patients with pulmonary fibrosis and is associated with hepatotoxicity and GI distress. It may be beneficial in patients with mild to moderate COVID-19-induced pulmonary fibrosis; however, additional research is necessary.

Knowledge, Attitude, and Acceptance of Sinopharm and AstraZeneca's COVID-19 Vaccines among Egyptian Population: A Cross-Sectional Study.

BACKGROUND: This study aimed to evaluate the Egyptian population's preference and awareness related to available COVID-19 vaccines and to determine different factors that can affect beliefs concerning these vaccines. METHODS: A cross-sectional web-based study was carried out among the general population in Egypt. Data collection was conducted via an online questionnaire. RESULTS: About 426 subjects participated in the survey. Vaccine preference is nearly equally even (50%) among all respondents. There was no significant difference in vaccine preference according to age, gender, residence, educational level, or social status. About 50% of public respondents mentioned that both AstraZeneca and Sinopharm vaccines do not offer protection against new variant COVID-19 strains. Healthcare workers are the lowest respondents to agree that vaccines offer protection against new COVID-19 variants (10.9%) compared to unemployed respondents (20.3%) and other professions (68.8%) with a statistically significant difference (p < 0.005). Safety of vaccine administration among children below 18 showed statistical differences for gender and educational level predictors. CONCLUSIONS: Most of the study population has satisfying knowledge about the COVID-19 vaccine. Continuous awareness campaigns must be carried out so that the people's background is updated with any new information that would help in raising the trust in vaccination.

Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.

BACKGROUND: Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS). MATERIALS AND METHODS: A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A included non-diabetic MBC patients treated with metformin in conjunction with chemotherapy and group B included those treated with chemotherapy alone. Both PFS and RR were used as a criteria to evaluate the treatment outcome. Associated adverse effects of metformin were also assessed. RESULTS: The average age of the participants in group A and group B was 50 vs. 47.5, respectively. No significant differences were detected between both cohorts concerning RR levels (regression disease (RD) 27.8% vs. 12.5%, stationary disease (SD) 44.4% vs. 41.7%, progression disease (PD) 27.8% vs. 45.8%, respectively, p = 0.074). Moreover, PFS showed no significant difference between both groups (p = 0.753). There was no significant correlation between metformin concentration and their adverse effects on the study participants. CONCLUSION: Metformin as an adjuvant therapy to MBC undergoing chemotherapy showed no significant survival benefit as determined by RR and PFS.

Evidence for the Efficacy of a High Dose of Vitamin D on the Hyperinflammation State in Moderate-to-Severe COVID-19 Patients: A Randomized Clinical Trial.

Background and Objectives: Vitamin D supplementation plays a key effect in lowering cytokine storms among COVID-19 patients by influencing the activity of the renin-angiotensin system and the production of the angiotensin-2 converting enzyme. The study was conducted to explore the effect of high-dose intramuscular vitamin D in hospitalized adults infected with moderate-to-severe SARS-CoV-2 in comparison with the standard of care in the COVID-19 protocol. Materials and Methods: Two groups of patients were compared in this prospective randomized controlled trial as the vitamin D was administered orally to group 1 (alfacalcidol 1 mcg/day) and intramuscularly to group 2 (cholecalciferol 200,000 IU). One hundred and sixteen participants were recruited in total, with fifty-eight patients in each group. Following the Egyptian Ministry of Health's policy for COVID-19 management, all patients received the same treatment for a minimum of five days. Results: A significant difference was recorded in the length of hospital stay (8.6 versus 6.8 days), need for high oxygen or non-invasive mechanical ventilator (67% versus 33%), need for a mechanical ventilator (25% versus 75%), clinical improvement (45% versus 55%), the occurrence of sepsis (35% versus 65%), and in the monitored laboratory parameters in favor of high-dose vitamin D. Moreover, clinical improvement was significantly associated with the need for low/high oxygen, an invasive/non-invasive mechanical ventilator (MV/NIMV), and diabetes, while mortality was associated with the need for MV, ICU admission, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and the occurrence of secondary infection. Conclusions: Our study showed that high-dose vitamin D was considered a promising treatment in the suppression of cytokine storms among COVID-19 patients and was associated with better clinical improvement and fewer adverse outcomes compared to low-dose vitamin D.

Perceptions and attitudes of ICU physicians toward antibiotics prescribing and resistance: A cross-sectional study.

BACKGROUND AND AIM: Antibiotic resistance is a major emphasis in intensive care units (ICUs). Better understanding of ICU physicians' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective interventions in fighting antimicrobial resistance in Egyptian ICUs and establishing a proper Antimicrobial Stewardship Program. METHODS: A cross-sectional questionnaire study was conducted including 92 physicians distributed across the different types of Egyptian healthcare institutions in two cities of Egypt; Cairo and El Monufia. Over a period of three months, started in December 2019 and ended in February 2020. RESULTS: A total of 92 Egyptian physicians were included in the study. Seventy (76.1%) of the surveyed physician strongly agreed and 22 (23.9%) agreed that antibiotic resistance is a worldwide problem. Moreover, 50 (54.3%) strongly agreed and 40 (43.4%) agreed that it is a problem in their hospitals while only 2 (2.1%) disagreed. Poor hand hygiene (67.5%), poor infection control practices by healthcare professionals (63.9%) as well as wrong practices in the management of invasive devices (68.7%), and poor environmental cleaning practices (63.4%) were considered very important causes of AMR by the majority of the surveyed ICU physicians. Almost all of the physicians (95%) rated an advice from a clinical pharmacist as very or moderately helpful intervention, while (52%) declared an advice from a microbiologist or an infectious disease specialist as very helpful. CONCLUSION: The results of the present study showed that the Egyptian ICU physicians have remarkable knowledge regarding antibiotic resistance as a worldwide problem and a high sensibility toward the problem in their hospitals. The study also showed that implementation of proper AMS is an urgent need as physicians answers for the different questions in the survey showed that their attitudes and perceptions regarding antibiotic resistance and their way in prescription could be modified and improved if AMS programs with suitable training programs and local guidelines are provided among different types of Egyptian hospitals.

The Impact of Sociodemographic, Nutritional, and Health Factors on the Incidence and Complications of COVID-19 in Egypt: A Cross-Sectional Study.

This study was intended to explore sociodemographic, nutritional, and health-related factors on the incidence of COVID-19 infection within the Egyptian population by assessing the frequency and determinants of post-COVID-19 symptoms and complications. A cross-sectional study using a structured survey on 15,166 participants was adopted. The results revealed common symptoms including fever (79.1%), cough (74.5%), anosmia& ageusia (68.4%), and dyspnea (66.9%). The patients were nonsmokers (83.9%), while 9.7% were mild smokers. The percentage of infected patients with comorbidities versus those without comorbidities were 29%, 71%, respectively. The highest incidence of infection was in those patients with hypertension (14.8%) and diabetes (10.9%), especially females with age >50 years and obesity (BMI; 30−39.9). The highest risks were observed for anticoagulants in the age above 50 years, morbid obesity, presence of comorbidities, and being a healthcare worker. The predictors of clot risk were in the age above 50 years, non-educated, and eating meat and eggs. Nonetheless, the highest risk of using antidepressants was in patients >50 years and those who traveled abroad. These findings and similarities within the surrounding region, the Middle East, North Africa, and South Europe, indicate the possibility of sharing the same viral strain and characteristics that may predict a similar vaccine efficacy and response.

A Battle against COVID-19: Vaccine Hesitancy and Awareness with a Comparative Study between Sinopharm and AstraZeneca.

BACKGROUND: Awareness about the COVID-19 vaccine's adverse effects is crucial for gaining public trust. As we still lack proof of vaccines' safety, this survey aimed to investigate Egyptians' general awareness of the Sinopharm and AstraZeneca vaccines against COVID-19 and provide considerable evidence on their side effects and complications. METHODS: A cross-sectional questionnaire-based study was conducted in Egypt between 20 September and 10 October in 2021, with multiple-choice questions (MCQs) covering all data on vaccine administration confusion, adverse effects or intensity, and complications. RESULTS: Among the 390 participants, 42.3% reported being hesitant before receiving one of the vaccines. About 40.3% of participants were previously infected before getting vaccinated while only 4.6% reported being infected after vaccination. The AstraZeneca vaccine demonstrated higher side effects and symptoms than the Sinopharm vaccine while the Sinopharm vaccine showed a significantly higher rate of COVID-19 infection after vaccination. CONCLUSIONS: People with higher educational levels and chronic respiratory diseases represent an excellent model for accepting COVID-19 vaccination. A booster shot is recommended for people vaccinated with the Sinopharm vaccine due to a significantly higher rate of COVID-19 infection after vaccination; however, the Sinopharm vaccine shows a more acceptable safety profile.

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 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.

Differential clinical diagnosis and prevalence rate of allergic rhinitis, asthma and chronic obstructive pulmonary disease among COVID-19 patients.

BACKGROUND: There is a great need to make a rapid differential clinical diagnosis of COVID-19 among respiratory disease patients and determining the prevalence rate of these diseases among the COVID-19 population. METHOD: Approximately 522 patients with allergic rhinitis, asthma, COPD, and COVID-19 were analysed for demographic and clinical features. Radiological features were analysed only for COVID-19 patients. RESULTS: COPD and asthma were more common among COVID-19 patients than allergic rhinitis. All chest CT scans of COVID-19 patients showed bilateral ground-glass opacity. Fever, dry cough, diarrhea, loss of sense of smell and taste, shortness of breath, and blue lips were significantly higher in all COVID-19 patients compared to COPD, asthma, and allergic rhinitis patients. CONCLUSION: The presence of clinical symptoms such as fever, dry cough, diarrhea, loss of sense of smell and taste, shortness of breath, and blue lips in COVID-19 patients, can be used for differential diagnosis between COVID-19 patients and other respiratory diseases. Then, the diagnosis can be confirmed by chest CT scan for COVID-19 patients without the need for a nasopharyngeal swab or PCR test, especially in epidemic countries. Allergic rhinitis patients are the least exposed to COVID-19 infection among other respiratory disease patients.

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.

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.

Inhaled salbutamol from aerolizer and diskus at different inhalation flows, inhalation volume and number of inhalations in both healthy subjects and COPD patients.

The aim of the present study was to demonstrate the effect of inhalation-flow, inhalation-volume and number of inhalations on aerosol-delivery of inhaled-salbutamol from two different dry powder inhalers (DPIs) in both healthy-subjects and chronic obstructive pulmonary disease (COPD) patients. Relative pulmonary-bioavailability and systemic-bioavailability of inhaled-salbutamol, delivered by Diskus and Aerolizer, was determined in 24-COPD patients and 24-healthy subjects. The healthy-subjects and the COPD-patients participated in the study for 7 days in which they received 4 study doses of 200 µg salbutamol (one slow-inhalation, two slow-inhalations, one fast-inhalation, and two fast-inhalations) in four alternative days with 24 hr washout period after each dose. Two urine-samples were collected from each study subjects. The first was provided 30 min post inhalation (USAL0.5), as an index of relative pulmonary-bioavailability, and the second was pooled to 24 hr post inhalation (USAL24), as an index of systemic-bioavailability. Fast-inhalation resulted in significantly higher USAL0.5 and USAL24 than slow-inhalation (p˂0.05) after one-inhalation in both healthy-subjects and COPD-patients but there was no significant difference between slow and fast-inhalation after two-inhalations. One-inhalation resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at both slow and fast-inhalation (p˂0.05) except USAL0.5 with Diskus at slow-inhalation there was no significant difference. Also, two-inhalations resulted in significantly higher USAL0.5 and USAL24 compared to one-inhalation at slow-inhalation only (p˂0.05). No significant difference was found between Aerolizer and Diskus except in USAL0.5 of one slow-inhalation in both health-subjects and COPD-patients (p = 0.048 and 0.047, respectively). Device-formula relation is present at low inhalation-flow since Diskus resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at slow inhalation than Aerolizer. It is essential to inhale-twice and as hard and deep as possible from each dose when using DPI especially with COPD-patients having poor inspiratory efforts such as elderly patients and children.

Total emitted dose of salbutamol sulphate at different inhalation flows and inhalation volumes through different types of dry powder inhalers.

The aim of the present study was to compare the performance of two different dry powder inhalers (DPIs) at different inhalations volumes and inhalation flows. Ventolin Diskus contain blisters of 200µg salbutamol. To test the TED from Aerolizer, salbutamol in Diskus blister was emptied and placed in size 3 capsules suitable for use with Aerolizer. Total emitted dose (TED) delivered by Diskus and Aerolizer was determined using DPI sampling apparatus after one and two inhalations from the same dose. 10-60L/min inhalation flows at 2 and 4L inhalation volume were used in the determination. At inhalation flow ≤30L/min, two inhalations resulted in higher TED than one inhalation (p < 0.05) and Diskus resulted in higher TED than Aerolizer (p < 0.05). The highest TED was at inhalation flow 40L/min above which the effect of the second inhalation and formula device relation were negligible. Device formula relation is present at low inhalation flow but at flow >30L/min Diskus drug formula can be delivered by Aerolizer with no significant difference in TED produced. For the best TED patients are required to inhale as fast as possible (a minimum of 40L/min). At lower inhalation flow two inhalations results in better emitted dose than one inhalation for both DPIs. So, we recommend patients with poor inspiratory efforts to inhale twice and as hard and deep as possible from each dose as they may not receive much benefit from one inhalation even when using DPI with low resistance (Aerolizer) or medium resistance (Diskus). However, further in-vivo study are required to validate this recommendtation.