30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE): A Prospective, International Collaborative Cohort Study.

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

Breast milk interleukin-7 and thymic gland development in infancy.

PURPOSE: Interleukin-7 (IL-7) is known to be important for lymphocyte development. We sought to investigate the maternal breast milk IL-7 expression to explore its impact on thymus development in infants. METHODS: We conducted a prospective study on three groups of healthy infants classified into exclusively breast-fed (n = 19), formula-fed (n = 17) and mixed-fed (n = 19) infants. They were investigated at 2, 4 and 6 months of age for thymic indices by ultrasonography, T lymphocyte subsets enumeration by flowcytometry and breast milk IL-7 levels. RESULTS: Thymic indices were higher at the age of 2 and 6 months in the exclusively breast-fed infants (mean ± SD 22.4 ± 2.1, 26.2 ± 2.7 mm3, respectively) and mixed-fed infants (mean ± SD 22 ± 3.2, 25 ± 3.2, respectively) as compared to formula-fed infants (mean ± SD 17.9 ± 3.7, 21.6 ± 3.9 respectively); p < 0.001. In the exclusively breast-fed infants, IL-7 levels correlated positively to thymic indices and CD3+ T cell numbers at 2 months of age. Positive correlations were elicited in the mixed-fed group at 2, 4 and 6 months of age for thymic indices and at 6 months for CD3+ cells. CONCLUSION: Breast milk and/or its IL-7 content have a significant positive impact on thymic development. Our conclusions are limited by the sample size and short duration of follow-up. What is known is that breast milk has a trophic role in thymic development and contains IL-7. What is new is that there is positive correlation between breast milk IL-7 concentration and thymic development and lymphocyte output; variation of IL-7 levels with type of feeding (exclusive breast feeding/mixed breast and formula feeding) and with time postnatally.

Influence of Health Literacy on Medication Adherence Among Elderly Females With Type 2 Diabetes in Pakistan.

Health literacy is how well the patients are able to attain, deal with, and understand basic health information. This is particularly important when it comes to comprehending prescribed medication instructions. To improve the communication strategies for health-care professionals during patient counseling, our study aimed to assess the influence of health literacy and medication adherence in older patients. The objectives of the study were to evaluate associations that occur between the level of health literacy and medication adherence. This study used a convenience sampling method of females (older than 60 years) attending the diabetic clinic in two hospital settings (N = 524). All study participants filled three validated questionnaires: these were the Literacy Assessment for Diabetes, the Diabetes Numeracy Test, and a modified Brief Adherence Rating Scale. To assess the spectrum of health literacy differences, we used χ2 analysis and linear regression analysis. Individuals with adequate health literacy were more likely to remember to take their medications compared with those with inadequate health literacy, χ2(4) = 11.6, p = .04. Adequate literacy level study participants were more likely to not change the dose of their medications without medical advice (12.3%) compared with those individuals with inadequate health literacy (2.8%), χ2(4) = 11.13, p = .03. The results in our study suggest that health-care professionals should focus on appropriate communication attuned to the assessment of health literacy levels particularly in older female patients when discussing medication instructions.

Inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during invasive mechanical ventilation.

BACKGROUND: Patient receiving invasive mechanical ventilation (IMV) may benefit from medical aerosol, but guidance on dosing with different aerosol devices is limited to in-vitro studies. The study was designed to compare aerosol delivery with five different types of aerosol generators during IMV. METHOD: In randomized design, 60 (30 female) mechanically ventilated chronic obstructive pulmonary disease (COPD) patients were assigned to one of 5 groups. Groups 1-4 received 5000 µg salbutamol using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO vibrating mesh and jet nebulizers (JN), respectively, while group 5 received 800 µg (8 puffs) of salbutamol via metered dose inhaler with AeroChamber-MV (MDI-AC). All devices were place in the inspiratory limb of ventilator downstream from humidifier which was switched off while delivery. Patients received the inhaled dose on day 1 and provided urine 30 post dosing. They also recived the same inhaled dose with a filter before the endotracheal tube on day 2. Amount of salbutamol excreted in urine 30 min post inhalation and the amount deposited on the filter from all the COPD patients were determined as indeces of pulmonary deposition and systemic absorption, respectively. RESULTS: No significant difference was found between the 3 vibrating mesh nebulizers (VMNs). The in-vivo and ex-vivo testing showed that all the VMNs resulted in better aerosol delivery compared to JN (p < 0.01). However, MDI-AC resulted in better aerosol delivery to VMNs but must be accompanied with careful attention and proper delivery of MDI-AC doses by healthcare provider. CONCLUSIONS: VMNs can be exchanged with each other, with no dose adjustment. However, dose adjustment is a must when replacing VMNs by JN or MDI-AC. This similarity and difference between the 5 aerosol delivery methods suggest that for IMV patients, aerosol delivery methods should be chosen or substituted with care.

ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt.

BACKGROUND: The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment. METHODS: The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS). RESULTS: Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10-3& 4.6×10-3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7-104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS. CONCLUSIONS: ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.

In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients.

Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

In vitro aerodynamic characteristics of aerosol delivered from different inhalation methods in mechanical ventilation.

Aerodynamic characteristics of aerosol delivery during invasive mechanical ventilation (IMV) are mostly determined by inserting cascade impactor in the circuit. Impactor might have some effect on airflow within IMV. Hence, the aim of the present study was to develop and evaluate new in vitro aerodynamic characterization methodology without affecting airflow in IMV. Breathing simulator was set in standard adult IMV circuit with inspiratory and expiratory pressures of 20 and 5 cm H2O, 1:3 inspiratory-expiratory ratio, 15 breaths min-1, and tidal volume of 500 ml. Two ml of salbutamol solution containing 10,000 µg was nebulized using three different vibrating mesh nebulizers (VMNs) and Sidestream jet nebulizer (JET). Sixteen-metered doses, containing 100 µg salbutamol each, were delivered using three different spacers. Each device was placed in inspiration limb of Y-piece of ventilator tubing. Aerodynamic characteristics of aerosol delivered were measured using cooled Andersen cascade impactor, with mixing inlet connected to it. VMNs used had significantly more total mass in the impactor (p < .001) and fine particle dose (p < .001) compared to JET. Spacers used had higher total mass in the impactor percent (p < .001) and fine particle fraction compared to nebulizers. The in vitro IMV methodology setting suggested here showed encouraging results in comparison of different aerosol delivery systems in intubated patient.

Adverse Drug Reaction Reporting Practices Among United Arab Emirates Pharmacists and Prescribers.

Background: Underreporting of adverse drug reactions (ADRs) has placed a heavy financial burden on health care resources worldwide. Realizing the importance of proper ADR reporting is paramount for implementing better patient care. Objective: This study was designed to assess knowledge, attitude, and practice (KAP) of ADR reporting among United Arab Emirates (UAE) health care professionals to clarify their present strategies and identify steps to avoid underreporting. Methods: A self-administered cross-sectional questionnaire was designed and randomly distributed to different health care personnel (n = 150). All participants were briefly informed about the aim of the study and given sufficient time to respond. The responses were collected over 6 months. The data were statistically analyzed for each reporter category (community pharmacist, hospital pharmacist, and doctors) using the chi-square test. Results: We found that 81%, 83%, and 83.3% of doctors, community pharmacists, and hospital pharmacists, respectively, were not aware of the existence of a reporting center and 56%, 60%, and 72% were not aware of a reporting procedure. Poor ADR reporting practices were shown by responders; only 19%, 14%, and 12.1% of doctors, community pharmacists, and hospital pharmacists reported ADRs. Conclusion: This study showed poor KAP results among health care professionals. Proper educational intervention strategies should be established in different health care settings for better patient care. With proper guidance, objectives in all health care settings should be targeted to positively change the concept of health care to consider ADR reporting as a common accepted daily routine practice.

Global 30-Day Morbidity and Mortality of Primary Bariatric Surgery Combined with Another Procedure: The BLEND Study.

BACKGROUND: No robust data are available on the safety of primary bariatric and metabolic surgery (BMS) alone compared to primary BMS combined with other procedures. OBJECTIVES: The objective of this study is to collect a 30-day mortality and morbidity of primary BMS combined with cholecystectomy, ventral hernia repair, or hiatal hernia repair. SETTING: This is as an international, multicenter, prospective, and observational audit of patients undergoing primary BMS combined with one or more additional procedures. METHODS: The audit took place from January 1 to June 30, 2022. A descriptive analysis was conducted. A propensity score matching analysis compared the BLEND study patients with those from the GENEVA cohort to obtain objective evaluation between combined procedures and primary BMS alone. RESULTS: A total of 75 centers submitted data on 1036 patients. Sleeve gastrectomy was the most commonly primary BMS (N = 653, 63%), and hiatal hernia repair was the most commonly concomitant procedure (N = 447, 43.1%). RYGB accounted for the highest percentage (20.6%) of a 30-day morbidity, followed by SG (10.5%). More than one combined procedures had the highest morbidities among all combinations (17.1%). Out of overall 134 complications, 129 (96.2%) were Clavien-Dindo I-III, and 4 were CD V. Patients who underwent a primary bariatric surgery combined with another procedure had a pronounced increase in a 30-day complication rate compared with patients who underwent only BMS (12.7% vs. 7.1%). CONCLUSION: Combining BMS with another procedure increases the risk of complications, but most are minor and require no further treatment. Combined procedures with primary BMS is a viable option to consider in selected patients following multi-disciplinary discussion.

Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial.

Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.

Identification of NS2B-NS3 Protease Inhibitors for Therapeutic Application in ZIKV Infection: A Pharmacophore-Based High-Throughput Virtual Screening and MD Simulations Approaches.

Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with -64.28, -55.15 and -50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

COVID-19's Psychological Impact on Chronic Disease Patients Seeking Medical Care.

BACKGROUND: The outbreak has harmed patients with multiple comorbidities and chronic conditions. The pandemic's psychological impact is thought to change their routine of seeking medical care. Research Question or Hypothesis: During COVID-19, patients with chronic conditions may experience anxiety, depression, and stress, and their pattern of seeking medical care may change. MATERIALS AND METHODS: In May 2021, a cross-sectional, web-based study of patients with chronic diseases was conducted. Eligible patients (1036) were assessed for psychological disorders, primarily depression, stress, and anxiety, using the DASS-21 scale, and their pattern of receiving medical care during COVID-19. RESULTS: During the pandemic, 52.5% of the patients with chronic diseases were depressed, 57.9% were anxious, and 35.6% were stressed. Patients with chronic diseases who had moderate to severe depression (34.9% versus 45.1%, p = 0.001), moderate to severe anxiety (43.6% versus 53.8%, p = 0.001), or moderate to severe stress (14.9% versus 34.8%, p = 0.001) were significantly more likely to have no follow-up for their chronic conditions. CONCLUSIONS: Patients with chronic conditions experienced significant anxiety, depression, and stress during COVID-19, which changed their pattern of seeking medical care, and the majority of them did not receive follow-up for their chronic conditions.

A Comparison of 3D Conformal and Deep Inspiratory Breath Holding vs. 4D-CT Intensity-Modulated Radiation Therapy for Patients with Left Breast Cancer.

BACKGROUND: Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. MATERIALS AND METHODS: This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. RESULTS: D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. CONCLUSIONS: Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.

Clinical Consequences for Individuals Treated with Tocilizumab for Serious COVID-19 Infection.

There seem to currently be no therapeutic medications found for the severe coronavirus infection in 2019 (COVID-19). In light of this, it has been hypothesized that the immunomodulatory treatment known as tocilizumab can lessen the inflammatory response that occurs in the respiratory system, speed up the process of clinical benefit, lower the risk of death, and avert the need for ventilators. This randomized controlled trial (RCT) studied patients with a proven infection of SARS-CoV-2 and hyperinflammatory reactions. The inclusion criteria included fever (body temperature > 38 °C), pulmonary infiltrates, or supplemental oxygen. The patients received either conventional treatment with one dose of either tocilizumab (8 mg per kilogram of body weight) or conventional treatment only. The subjects were randomized to receive either treatment with a 1:1 ratio. A time-to-event test was conducted to determine the time to intubation or death. There was an insignificant difference between the investigated groups regarding the time to death, time to mechanical ventilation, and percentage of deaths. The conventional group's median (IQR) hospital length of stay was 4 (3-6) days, whereas the tocilizumab therapy group was 7 (4.75-10) days. There was a substantial difference in the mechanical ventilation rates in both groups, which were 17 (34%) and 28 (56%), respectively. In hospitalized patients with severe illness and COVID-19, tocilizumab was ineffective in preventing intubation or death. Trials must be larger, however, in order to exclude the potential benefits or harms.

COVID-19 Booster Doses: A Multi-Center Study Reflecting Healthcare Providers' Perceptions.

(1) Background: During 2019, the COVID-19 pandemic was threatening healthcare services and workers, and acquiring immunity was an option to stop or limit the burden of this pandemic. Herd immunity was a top priority worldwide as the virus was spreading rapidly. It was estimated that 67% of the total global population should be immunized against COVID-19 to achieve herd immunity. The aim of the current study is to investigate different perceptions of healthcare workers in the Kingdom of Bahrain and Egypt using an online survey in an attempt to evaluate their awareness and concerns regarding new variants and booster doses. (2) Methods: This study conducted a survey on healthcare workers in the Kingdom of Bahrain and Egypt about their perception and concerns on the COVID-19 vaccines. (3) Results: The study found that out of 389 healthcare workers 46.1% of the physicians were not willing to take the booster doses (p = 0.004). Physicians also did not support taking the COVID-19 vaccine as an annual vaccine (p = 0.04). Furthermore, to assess the association between the type of vaccine taken with the willingness of taking a booster vaccine, healthcare workers beliefs on vaccine effectiveness (p = 0.001), suspension or contact with patients (p = 0.000), and infection after COVID-19 vaccination (p = 0.016) were significant. (4) Conclusion: Knowledge about vaccine accreditation and regulation should be dispersed more widely to ensure that the population has a positive perception on vaccine safety and effectiveness.

Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate.

AIM: Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHOD: Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 µg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10,100 µg inhalations from a Qvar(®) Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 µg inhalations from a Clenil(®) pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone-17-monopropionate (17-BMP) and beclometasone (BOH) were measured. RESULTS: No BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSION: The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies.

Evaluation of perceived fears of COVID-19 virus infection and its relationship to health-related quality of life among patients with diabetes mellitus in Egypt during pandemic: a developing country single-center study.

AIMS/INTRODUCTION: COVID-19 pandemic and its associated circumstances had adversely affected patients with chronic diseases. This study aimed to assess the health-related quality of life (QoL), and identify its psychological and clinical correlates in patients with diabetes mellitus (DM) during pandemic in Egypt. MATERIALS AND METHODS: A cross-sectional study, using a convenience sampling technique, was conducted among patients with DM who were recruited from Zagazig University endocrinology outpatient clinics, Sharkia Province, Egypt from June 30 to September 29, 2020. A total of 200 consecutive patients were interviewed using a semistructured demographic and clinical checklist, the fear of COVID-19 scale (FCV-19S), the Hospital Anxiety and Depression Scale (HADS), and the short form 36 (SF-36) health survey. RESULTS: Poor physical and mental QoL was reported in 64% and 62% of patients with DM, respectively. Female gender, increased mean arterial pressure (MAP), associated physical comorbidities, and depressive symptoms were associated with lesser odds of physical QoL (OR 0.46, 0.96, 0.29, and 0.88, respectively). Besides, female gender, associated physical comorbidities, fear of COVID-19 virus infection (FCV), and depressive symptoms were associated with lesser odds of mental QoL (OR 0.41, 0.36, 0.91, and 0.84, respectively). The FCV was inversely correlated with all items of SF-36 among patients. CONCLUSION: QoL, either physical or mental, was adversely affected among patients with DM during pandemic. FCV was negatively correlated with all QOL domains. Longitudinal studies are warranted to explore the long-term effect of pandemic on the physical and mental well-being of patients with DM.

Cognitive after-effects and associated correlates among post-illness COVID-19 survivors: a cross-sectional study, Egypt.

Background: COVID-19's after-effects among survivors are of increased concern. The cognitive aftermath of COVID-19 virus infection was underrated. This study aimed to identify and compare the cognitive impairment (CI) and its correlates among COVID-19 survivors and control subjects. A total of 85 adults who survived COVID-19 virus infection and an equal number of control subjects (matched for age, sex, education, and socioeconomic level) were included in this study. They were recruited from Zagazig University Hospitals, Sharkia Province, Egypt. All subjects were interviewed utilizing a semistructured demographic and clinical checklist, the Montreal Cognitive Assessment (MoCA) test, and the Hospital Anxiety Depression Scale (HADS). Results: More than half of COVID-19 survivors experienced CI (compared to only 8% of control subjects). Individuals who survived COVID-19 virus infection were more likely to have impairments in visuo-executive functions (OR: 0.3, 95% CI 0.2-0.5), attention (OR: 0.4, 95% CI 0.3-0.7), language (OR: 0.2, 95% CI 0.1-0.5), delayed recall (OR: 0.5, 95% CI 0.4-0.6), and total MoCA Scores (OR: 0.1, 95% CI 0.04-0.2). Among COVID-19 survivors, those who experienced CI were likely to be older (OR: 1.1, 95% CI 1.03-1.2), and of low-to-moderate education (OR: 4.9, 95% CI 1.6-15.1). Conclusions: CI was prevalent among COVID-19 survivors. The visuo-executive functions, attention, language, and delayed recall were the most affected domains. Older age and lower educational level predicted CI in COVID-19 survivors.

Sleep disturbances following recovery from COVID-19: a comparative cross-sectional study in Egypt.

BACKGROUND: Sequelae from COVID-19 are increasingly being reported, but sleep disturbances after recovery from the disease have had little attention. AIMS: This study aimed to identify and compare sleep disturbances and associated correlates among adults who have recovered from COVID-19 with those who have never been infected with the disease. METHODS: The sample included 85 adults who have recovered from COVID-19 and 85 adults who have never been infected (matched on age, sex, education and socioeconomic level). Individuals were recruited from Zagazig University Hospitals, Egypt from 1 September to 29 November 2020. Participants were interviewed using a sociodemographic and clinical checklist, the Pittsburgh Sleep Quality Index and the Hospital Anxiety Depression Scale. RESULTS: Most (77%) of the recovered cases had experienced sleep disturbances, compared with 46% of controls. Individuals who had recovered from COVID-19 were more likely to have poor subjective sleep quality (odds ratio (OR) 1.5, 95% confidence interval (CI): 1.1-2.1), prolonged sleep latency (OR 1.8, 95% CI: 1.3-2.6), shorter sleep duration (OR 1.6, 95% CI: 1.1-2.2), reduced sleep efficiency (OR 3.8, 95% CI: 2.0-7.1), frequent daytime dysfunction (OR 1.9, 95% CI: 1.2-3.1) and poor global Pittsburgh Sleep Quality Index score (OR 3.0, 95% CI: 1.5-6.0). Depressive (P = 0.002) and anxiety (P = 0.003) symptoms were associated with a poor global Pittsburgh Sleep Quality Index score among recovered female participants (P = 0,034) who had low-to-medium education level (P = 0.004). CONCLUSIONS: Further studies (e.g. population-based longitudinal studies) are needed on sleep disturbances as a potential sequelae of COVID-19, because it can impair mental and physical well-being.