Effect of different accessory devices on the dose delivered from pressurised metred-dose inhalers.

INTRODUCTIONS: Improved aerosol delivery of bronchodilators to chronic obstructive pulmonary disease (COPD) subjects is a cornerstone in the treatment approach. Drug delivery and response are improved with the use of accessory devices [spacers and valved holding chambers (VHCs)] with metred-dose inhalers (pMDIs). However, different accessory devices are available in the market with different properties that could affect aerosol delivery. Thus, this study aimed to assess the relative lung deposition and systemic bioavailability and compare bronchodilator response of salbutamol delivered using different accessory devices attached to pMDIs. METHODS: Twelve healthy subjects and twelve COPD subjects inhaled 300 µg salbutamol (3 pMDI puffs) using five different accessory devices with either masks or mouthpieces (Able, Aerochamber plus flow Vu, Dolphin chamber, Tipshaler spacer, and modified Drink bottle spacer). Urine samples were collected thirty minutes post-dosing and cumulatively for the next twenty-four hours, to determine and compare the relative lung deposition [0-0.5 hour excretion of urinary salbutamol (USAL0.5)] and systemic bioavailability [0.5-24 hours excretion of urinary salbutamol (USAL24)] of salbutamol from the selected accessory devices. Also, the difference between pre and post-inhalation forced expiratory volume in one second (ΔFEV1 %) of predicted was determined for each accessory device. RESULTS: Urinary excretion of salbutamol (both USAL0.5 and USAL24 samples) in COPD subjects was significantly (P < .05) lower than in healthy subjects for all accessory devices. USAL0.5 and USAL24 in non-antistatic spacers (modified Drink bottle spacer and Dolphin chamber spacers) were significantly lower (P < .05) than that for antistatic spacers (Aerochamber plus flow Vu, Able and Tips-haler). No significant difference in USAL0.5 and USAL24 was observed between facemasks and mouthpieces. There was a significant difference (P < .05) in ΔFEV1 % of predicted values between COPD subjects and healthy subjects. However, within the COPD group and the healthy group there was no significant difference in ΔFEV1 % of predicted values between all accessory devices or between with mouthpiece or with a mask. CONCLUSIONS: COPD subjects had lower aerosol delivered compared with healthy subjects. Anti-static accessory devices delivered a higher amount of aerosol compared with non-antistatic accessory devices. Even though the presence of a significant difference in aerosol delivery between non-antistatic and antistatic accessory devices no significant difference was found in the ΔFEV1 % between all accessory devices.

Recent therapeutic targets in diabetic nephropathy.

BACKGROUND: The prevalence of diabetes mellitus has been increased dramatically which in turn leads to complications including cardiovascular diseases, diabetic kidney disease, and substantially end-stage renal disease. METHODS: We reviewed articles discussing the pathophysiology of diabetic nephropathy with new agents that may be useful in the management of the disease. We used PubMed, Scopus, Google Scholar and the Open-access searching engines. RESULTS: The recent recommendations primarily depend on glycaemic and blood pressure control and the use of standard renin-angiotensin system blockade. Currently, the use of agents with nephroprotective effects beyond the hyperglycaemic lowering effect has been evidenced clinically. CONCLUSIONS: In his review, the pathophysiology, clinical manifestations, and lines of treatment of diabetic nephropathy are discussed. In addition, a focus on the clinical role and nephroprotective effects of the emerging therapeutic class, dipeptidyl peptidase IV (DPP-4) inhibitors, is addressed in detail.

Effect of ciprofloxacin vs levofloxacin on QTc-interval and dysglycemia in diabetic and non-diabetic patients.

BACKGROUND: Levofloxacin and ciprofloxacin are more commonly used amongst fluoroquinolone class and the question of cardiac safety and glucose hemostasis of this class has been raised. OBJECTIVE: To compare intravenous levofloxacin and ciprofloxacin regarding their risk on QTc prolongation and dysglycemia in diabetic and non-diabetic patients. METHODS: A randomised prospective study at Beni-Suef university hospital was conducted on 200 adult patients over 6 months. The patients received intravenous levofloxacin 750mg once daily or ciprofloxacin 400mg twice daily. Electrocardiogram and fasting blood glucose were obtained from each patient before starting the antibiotic, 24 hours, 72 hours after the first dose, and 72 hours after antibiotics cessation. RESULTS: The results of the current study showed the relative risk for QTc prolongation with levofloxacin was more than ciprofloxacin by about 4 and 1.5 times in diabetic and non-diabetic patients, respectively. The relative risk for dysglycemia with levofloxacin was 2.28 and 1.39 times more than ciprofloxacin in diabetic and non-diabetic patients, respectively. CONCLUSION: The present study showed that the risk for QTc prolongation and hyperglycemia was greater with levofloxacin than ciprofloxacin in diabetic and non-diabetic patients. In addition, the risk for hypoglycemia was greater with levofloxacin than ciprofloxacin in non-diabetic patients.

Clinical and hemodynamic effects of oral sildenafil on biventricular function on patients with left ventricular systolic dysfunction.

BACKGROUND: We explore the dual benefits of sildenafil on bi-ventricular functions in the form of improvement of ejection fraction, pulmonary vascular resistance and functional capacity of systolic heart failure patients either related to dilated or ischemic cardiomyopathy. AIM OF THE WORK: To evaluate the effect of oral sildenafil on biventricular function in patients with left ventricular systolic dysfunction. PATIENTS AND METHODS: The prospective randomised case-control study included 80 patients with left ventricular systolic dysfunction resulting from dilated or ischemic cardiomyopathy were equally randomised to one of the treatment groups in (1:1) who were collected from the outpatient clinic of cardiac care unit (CCU) of Beni-Suef University hospital; each group contained 40 patients: The first group (control group): received the guideline-recommended treatment of heart failure with reduced ejection fraction which consists of [angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), beta-blockers, aldosterone receptor antagonist, digoxin]. The second group (sildenafil group): received the previously mentioned guideline-recommended treatment in the control group plus sildenafil 25 mg three times per day. All patients were subjected to detailed history taking, baseline transthorathic echocardiography and exercise ECG using the Naughton protocol. Follow-up transthorathic echocardiography and exercise ECG was conducted after 3 months. RESULTS: Sildenafil improves heart failure symptoms such as dyspnea or orthopnea or increasing the functional capacity of myocardium which is measured by estimated metabolic equivalents of task (METS) (P = .017), and exercise duration (P = .013). Sildenafil increased cardiac output (P = .033), which is considered one of the desirable targets in heart failure patients. CONCLUSION: In patients with left ventricular systolic dysfunction secondary to dilated or ischemic cardiomyopathy, relatively small doses of sildenafil significantly enhances exercise period and functional ability, with substantial improvement in left ventricular systolic function irrespective of the existence of major pulmonary hypertension.

Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control.

BACKGROUND: Preclinical data illustrated that the dipeptidyl peptidase-4(DPP-4) inhibitors did lower urinary albumin excretion in diabetes-induced rats. We evaluated the effects of saxagliptin and vildagliptin on albuminuria in patients with diabetic nephropathy on top of the renin-angiotensin-aldosterone system (RAAS) blockade therapy. METHODS: This study included 120 patients with type 2 diabetes (T2D), hypertension, and prevalent albuminuria [defined as urine albumin-to-creatinine ratio (UACR) 30-3000mg/g creatinine] on a stable dose of olmesartan as a standard RAAS blocker for diabetic nephropathy. Patients were assigned to receive either of saxagliptin 5mg/day (n = 40), vildagliptin 100mg/day (n = 40), or traditional antidiabetic therapy as control patients (n = 40) for 12 weeks. RESULTS: Each of saxagliptin and vildagliptin significantly reduced albuminuria after 12 weeks, with mean percentage changes (%) of -57.9% [95% confidence interval (CI) -66.1 to -49.8], and -55.2% (95% CI -64.9 to -45.4); P < .001, respectively, compared with the control group. Significantly, saxagliptin shifted higher proportions of patients towards lower albuminuria categories (P < .001) compared with vildagliptin despite a similar UACR rate of changes. Results of binary logistic models confirmed that the change in UACR because saxagliptin was independent of changes in systolic blood pressure (SBP), glycated hemoglobin (HbA1c ), estimated glomerular filtration rate (eGFR), or body weight (overall regression: P = .002, R2  = 0.398) vs control. Likewise, vildagliptin reduced UACR independently on other confounders (overall regression: P = .002, R2  = 0.388). Furthermore, no significant correlation was observed between the change in UACR and changes in HbA1c, SBP or eGFR with either saxagliptin or vildagliptin (Pearson coefficients: 0.203, 0.143, -0.190; P > .05, and 0.003, 0.241, 0.019; P > .05, respectively). CONCLUSIONS: DPP-4 inhibitors, saxagliptin, and vildagliptin, resulted in substantial reductions in albuminuria in patients with T2D and hypertension on top of RAAS blockade after short term therapy independently on glycaemic or hemodynamic changes. Saxagliptin was superior to vildagliptin in albuminuria-categorical shifting.

The effect of Clip-tone® and its smartphone application on optimisation of metered-dose inhalers inhalation technique.

BACKGROUNDS: Although metered-dose inhalers (pMDI) therapy is convenient and widely prescribed, its use usually results in repetitive inhalation technique errors. One of the most repetitive errors is inhaling too fast through the pMDI. The present study aimed to evaluate the effect of Clip-tone® along with smartphone visual feedback application on the subject's inhalation time. METHODS: Two hundred subjects were included in the study. They were randomised into four groups. Group 1 received only verbal counselling; group 2 received verbal counselling with resistance (a modified Clip-tone® that does not produce whistle attached to their pMDI); group 3 received verbal counselling plus whistle (as audio feedback) from ordinary Clip-tone® and group 4 received verbal counselling plus audio feedback (whistle) from Clip-tone® and visual feedback (smartphone application). Inhalation time through the pMDI for each subject was recorded three times and inter and intra-subjects variations were calculated. RESULTS: Verbal counselling plus audio feedback and verbal counselling plus audio and visual feedbacks groups had 45/50 (90%) and 37/50 (74%) subjects respectively, having correct inhalation flow (inhaling at between 3 to 7 seconds). Verbal counselling plus audio feedback and verbal counselling plus audio and visual feedbacks groups' inter and intra-subjects variations were lower than that of verbal counselling and verbal counselling with resistance groups which had 28/50 (52%) and 20/50 (40%) subjects respectively, with inhalation time between 3 and 7 seconds. CONCLUSIONS: Providing audio feedback by the Clip-tone® along with smartphone visual feedback application maintained the deep and slow inhalation through pMDI much better compared to verbal counselling only. We recommend the patients to take all their inhaled doses using pMDI attached to a training device like Clip-tone® along with a smartphone visual feedback application for optimisation of the aerosol delivery from the pMDI.

Lung deposition and systemic bioavailability of dose delivered to smoker compared with non-smoker COPD subjects.

INTRODUCTION: Inhaled drugs are the most commonly used class of medications for COPD subjects. No studies have been performed to assess the influence of smoking on lung deposition of aerosolized medication, especially for the exacerbated COPD subject. The present study aimed to assess the influence of smoking on the lung deposition of the aerosol delivered to exacerbated COPD subjects. METHODS: Twenty-four exacerbated COPD subjects using automatic continuous positive airway pressure (Auto-CPAP), 12 smokers (six females) and 12 non-smokers (six females) were recruited in the study. The subjects participated in the study received four salbutamol study doses; 1200 µg (12 puffs 100 µg/puff) of salbutamol emitted from pMDI canister connected to AeroChamber MV spacer; 1200 µg of salbutamol emitted from pMDI canister connected to Combihaler spacer; 1 mL of salbutamol respirable solution (5000 µg/mL) nebulized by Aerogen Solo connected to its T-piece; and 1 mL of salbutamol respirable solution nebulized by Aerogen Solo connected to Combihaler spacer with 2 puffs salbutamol MDI (200 µg salbutamol) before nebulisation. The subjects were randomised to receive the four selected dose-adaptor combination in a sealed envelope design on days 1, 3, 5 and 7. A washout period of 24 hours was provided between each salbutamol dosing. Auto-CPAP was adjusted at non-invasive ventilation mode with the integrated heated humidifier, as a source of humidity. Urine samples were provided by subjects, 30 minutes and cumulatively 24 hours post inhalation, as an index of the relative and systemic bioavailability, respectively, and aliquots were retained for salbutamol analysis using solid-phase extraction and high-performance liquid chromatography (HPLC). On day 2 of the study, a collecting filter was placed between the aerosol generator and the subject's mask so that the subjects would not inhale the salbutamol delivered. The same study doses and/or adapters were delivered to each subject, with filters changed with each dose-adapter combination. Salbutamol entrained on the filter was desorbed to be analysed by the HPLC. RESULTS: Significantly higher lung deposition (30 minutes urinary salbutamol) was detected with the non-smoker compared with smokers (P < .05). Significantly higher systemic bioavailability (pooled 24-hour urinary salbutamol) for smokers compared with non-smokers was found with Aerogen Solo connected to its T-piece and CombiHaler spacer with pMDI (P < .05) only. Significantly higher amount desorbed from the ex-vivo filter were found from pMDI with both spacers in non-smokers (P < .05) compared with the smokers. CONCLUSION: The study demonstrated that smoking reduced the lung deposition of inhaled salbutamol delivered by nebulizer or pMDI. However, the smoking effect on cytochrome p450 was observed to increase systemic absorption of the ingested portion of the inhaled dose. The lower lung deposition and possible higher systemic absorption should be taken into consideration while prescribing inhaled medication to COPD smokers especially exacerbated patients that need ventilation. Further studies are needed.

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.

Design, optimization, characterization, and in vivo evaluation of sterosomes as a carrier of metformin for treatment of lung cancer.

The present study aimed to formulate and evaluate metformin sterosomes. Sterosomes were prepared by incorporating stearylamine and cholesterol in different ratios. Sterosomes were characterized using size, zeta potential, entrapment efficiency (EE%) and in vitro release. Aerosol generated by nebulization was evaluated by a cooled Andersen cascade impactor (ACI) at 15 L/min. In vitro cytotoxicity of free and metformin-containing sterosomes was tested against human cancer cell lines. A comparative pharmacokinetic study between sterosomal formulation and free drug solution (750 mg) was performed. Spirometry was performed before and at time intervals after inhalation. The mean hydrodynamic diameter of the formulated vesicles was in the range of 288.7-578 nm. The EE% varied from 71 ± 1.4% to 89 ± 5.2%, with an optimum EE% of 89 ± 5.2at a lipid ratio of 2/1 stearylamine/cholesterol. Metformin sterosomes displayed an inhibitory effect on A549 lung cancer cell lines which significantly (p < 0.05) increased depending on dose and prolonged exposure time. Spirometric data were minimally changed before and after inhalation without a statistically significant difference in the forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or FEV1/FVC ratio (p > 0.05). Metformin-loaded sterosomes resulted in a significant increase in biological half-life (t1/2) with a mean value of 7.31 ± 1.04 h compared to 3.99 ± 0.17 h of the solution form. However, the peak plasma concentration of metformin sterosomes was lower than that achieved by metformin-free solution aerosol, and the difference was statistically significant (p < 0.05).The eligibility of sterosomes for aerosol delivery by nebulization would provide a novel strategy for delivery of metformin by inhalation as a potentially effective inhalation treatment of lung cancer.

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.

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.

Manuka combinations with nigella sativa and hydroxyurea in treating iron overload of pediatric ß-thalassemia major, randomized clinical trial.

Background: ß-thalassemia major is microcytic hypochromic anemia disorder inherited from parents, resulting from a mutation in the ß-globin locus. As a result, a quantitative defective hemoglobin synthesis and relative excess in α-globin is occurred. As such, frequent blood transfusion is required, that leads to iron overload. Iron overload results in several pathological complications, including cell death, tissue injury, organ dysfunction, and liver fibrosis. The present study examined the effectiveness of nigella Sativa and manuka honey combination or manuka honey alone to the conventional therapy (Deferasirox + blood transfusion) used for preventing and managing iron overload in pediatric ß-thalassemia major patients. Methods: One hundred sixty-five patients participated in this randomized, double-blind, standard therapy-controlled, parallel-design multisite trial. The patients were randomly allocated into three groups, receiving either 500 mg nigella sativa oil combined with manuka honey lozenge (344 mg) daily or manuka honey alone plus the conventional therapy for ten treatment months. Ferritin level, serum iron, transferrin saturation, total iron binding capacity, alanine transaminase, and aspartate transaminase were determined at baseline and month 10. Results: Eventually, serum ferritin and iron were decreased significantly in the nigella sativa + manuka honey group as compared with the control group. Other clinical parameters were significantly impacted. The level of alanine transaminase and aspartate transaminase were significantly decreased in the nigella sativa plus manuka honey group compared with the control group. Conclusion: Results showed that nigella sativa plus manuka honey was more effective than manuka alone or the conventional treatment alone in managing iron overload of ß-thalassemia major patients.

Predictors of methotrexate adherence and patient's awareness of it in rheumatoid arthritis and its effect on quality of life.

Introduction: Adherence studies among rheumatoid arthritis (RA) patients, in Egypt and throughout the Middle East region, are lacking. This study aimed to evaluate methotrexate (MTX) adherence in Rheumatoid arthritis (RA) patients and to identify specific non-adherence predictors. Methods: A cross-sectional observational study included 300 RA patients who were administered MTX for at least one year. The survey was completed through direct interviews. The demographic patient data were collected (age, education, sex, work status, disease duration, duration of MTX administration and current dose). Patients' adherence to MTX predictors for non-adherence, MTX side effects and functional disability were assessed in the study. Results: Majority of respondents showed good MTX adherence, and more than 50% of patient's experienced MTX side effects. A large percentage of participants showed low knowledge about MTX nature and side effects. Most participants reported no or some difficulty in quality of life-related activities and functional disability. Conclusion: MTX adherence and awareness were positively correlated to many variables, including, age, educational level and disease duration, which in turn has its positive impact on the patient's quality of life. Still, more research is needed to determine the impact of non-adherence on the patient's health outcomes.

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.

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.

The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial.

Recently, several clinical trials have attempted to find evidence that supports the anticancer use of metformin in breast cancer (BC) patients. The current study evaluates the anticancer activity of metformin in addition to neoadjuvant chemotherapy (NACT) in locally advanced BC patients. Additionally, we assess the safety and tolerability of this combination and its effect on the quality of life (QoL) of BC patients. Eighty non-diabetic female patients with proven locally advanced BC were randomized into two arms. The first arm received anthracycline/taxane-based NACT plus metformin. The second arm received anthracycline/taxane-based NACT only. Overall response rate (ORR), clinical complete response (cCr), pathological complete response (pCR), and breast conservative rate (BCR) were evaluated between both groups, and correlated with serum metformin concentration. ORR, cCr, pCR, and BCR increased non-significantly in the metformin group compared to the control group; 80.6% vs 68.4%, 27.8% vs 10.5%, 22.2% vs 10.5%, and 19.4% vs 13.2%, respectively. A trend towards cCR and pCR was associated with higher serum metformin concentrations. Metformin decreased the incidence of peripheral neuropathy, bone pain, and arthralgia, although worsened the gastrointestinal adverse events. Metformin combination with NACT has no effect on the QoL of BC patients. Metformin combination with NACT is safe, tolerable, and improves non-significantly the clinical and pathological tumor response of BC patients.