Body composition analysis using dual-energy x-ray absorptiometry in an Egyptian pediatric sickle cell disease cohort.

BACKGROUND: Growth failure is commonly encountered in sickle cell disease (SCD). Tissue compartment growth and development are subsequently likely to be altered in such patients. OBJECTIVE: We aimed to analyze body composition in an Egyptian pediatric SCD cohort using dual-energy x-ray absorptiometry (DEXA), one of the most comprehensive and noninvasive assessment methods available. METHODS: Forty children with SCD ≤18 years and 40 healthy youngsters age- and gender-matched were enrolled. Patients' demographic, clinical, and laboratory parameters were obtained from their archived files. All patients and controls were subjected to body composition assessment using a MedixDR-Whole Body DEXA System. RESULTS: In SCD patients; weight and height relative to age Z scores were significantly lower (p < .001), total body lean was significantly higher (p = .006), and total body fat percentage was lower, yet the difference was not statistically significant (p = .09). There were no statistically significant variations in bone mineral density or content, basal metabolic rate, subcutaneous adipose tissue, android/gynoid fat ratio, and visceral adipose tissue. There were no significant gender disparities between SCD patients and controls. CONCLUSION: Faltering growth in children with SCD should be addressed with a multidisciplinary approach including nutritional support, correction of anemia, and proper medical care. Body composition parameters assessed using DEXA were comparable between cases and controls apart from total body lean. Further clinical studies are needed with multicenter cooperation and a larger sample size to assess the usefulness of DEXA as an assessment tool for body composition in children with SCD.

The Effects of Distance, Time, and Nonspatial Factors on Hemodialysis Access in Qatar.

Background A long distance and time spent traveling to a hemodialysis (HD) center and other factors, such as comorbidities, can significantly impact HD patient compliance, satisfaction, and cost. Uncertainty about HD-dependent patients' geographical location may lead to inappropriate distribution of HD centers. The present study investigates travel time, distance, and nonspatial factors affecting HD center accessibility within a 30-km radius in the State of Qatar. Materials and methods The study included all HD-dependent patients residing in Qatar between March 1, 2020, and December 31, 2021. There were 921 patients dialyzed in six HD centers across Qatar. Our methodology incorporated descriptive and analytical cross-sectional designs to accurately identify the shortest routes and quickest travel times. We used two applications (Maptive {Vancouver, WA: BatchGeo LLC} and Google Maps {Mountain View, CA: Google LLC}) and marked a driving distance of 30 km as the main assessment scale and measurement standard, allowing optimum spatial accessibility determination. Results On average, patients traveled approximately 19±4.2 km, requiring almost 17.6±3.4 minutes to reach the assigned HD center three times per week. Based on geographic-spatial accessibility analysis, patients living in Umm Salal drove 31.4±3.5 km in 32.4±4.7 minutes, Al Daayen patients drove 30.2 km in 25.3 minutes, and others even drove more than 70 km to access HD sessions. Approximately 37.8% of Qatar's municipalities had no HD centers within their boundaries, but nearly 47% of HD-dependent patients lived in those municipalities. Additionally, some municipalities had HD centers; however, their general population density was less than 100 inhabitants/km2, and they had relatively few patients requiring regular HD. We noted a statistically significant correlation between the patients' residences and the locations of HD centers, whether they were located within or outside municipalities. Also, nonspatial factors may have affected the likelihood of reaching a hemodialysis center within a 30-km distance, including two or more comorbid conditions, having HD for at least five years, living in a municipality with more than 1,000 inhabitants/km2, being female, and attending dialysis centers that are more than 30 km away. Conclusion Although the available HD centers were sufficient for the present number of patients requiring HD, HD center locations did not match the patients' distribution, leading to difficulties for some patients. Understanding the impact of this geographic mismatch, population density, and other spatial factors helps significantly improve patient care and satisfaction at minimal cost. Furthermore, considering all these factors is crucial when planning new centers to achieve higher satisfaction and compliance as well as better health care.

Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.

BACKGROUND: Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. METHODS: This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). RESULTS: 842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus (p = 0.001 and p = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, p < 0.0001, and 95% CI 1.128-2.272, p < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, p < 0.007, and 95% CI 1.092-1.270, p < 0.0001, respectively). CONCLUSION: Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.

Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

From past to present: Exploring COVID-19 in Qatar's hemodialysis population across Omicron dominant and pre-Omicron periods.

COVID-19 carries a high risk of morbidity and mortality in dialysis patients. Multiple SARS-CoV-2 variants have been identified since the start of the COVID-19 pandemic. The current study aimed to compare the incidence and outcomes of the COVID-19 Omicron dominant period versus other pre-Omicron period in hemodialysis patients. In this observational, analytical, retrospective, nationwide study, we reviewed adult chronic hemodialysis patients between March 1, 2020, and January 31, 2022. Four hundred twenty-one patients had COVID-19 during the study period. The incidence of COVID-19 due to the Omicron dominant period was significantly higher than other pre-Omicron period (30.3% vs. 18.7%, P<0.001). In contrast, the admission rate to ICU was significantly lower in the Omicron dominant period than in the pre-Omicron period (2.8% vs. 25%, P<0001) but with no significant difference in ICU length of stay. The mortality rate was lower in the Omicron dominant period compared to the pre-Omicron period (2.4% vs. 15.5%, P<0.001). Using multivariate analysis, older age [OR 1.093 (95% CI 1.044-1.145); P<0.0001] and need for mechanical ventilation [OR 70.4 (95% CI 20.39-243.1); P<0.0001] were identified as two independent risk factors for death in hemodialysis patients with COVID-19. In Conclusion, the COVID-19 Omicron variant had a higher incidence and lower morbidity and mortality than pre-Omicron period in our hemodialysis population.

Optimal energy management applying load elasticity integrating renewable resources.

Urban growth aimed at developing smart cities confronts several obstacles, such as difficulties and costs in constructing stations and meeting consumer demands. These are possible to overcome by integrating Renewable Energy Resources (RESs) with the help of demand side management (DSM) for managing generation and loading profiles to minimize electricity bills while accounting for reduction in carbon emissions and the peak to average ratio (PAR) of the load. This study aims to achieve a multi-objective goal of optimizing energy management in smart cities which is accomplished by optimally allocating RESs combined with DSM for creating a flexible load profile under RESs and load uncertainty. A comprehensive study is applied to IEEE 69-bus with different scenarios using Sea-Horse Optimization (SHO) for optimal citing and sizing of the RESs while serving the objectives of minimizing total power losses and reducing PAR. SHO performance is evaluated and compared to other techniques such as Genetic Algorithm (GA), Grey Wolf Optimization (GWO), Whale Optimization (WO), and Zebra Optimization (ZO) algorithms. The results show that combining elastic load shifting with optimal sizing and allocation using SHO achieves a global optimum solution for the highest power loss reduction while using a significantly smaller sized RESs than the counterpart.

Game-based intradialytic non-weight-bearing exercise training on gait speed and balance in older adults with diabetes: a single-blind randomized controlled trial.

Older adults with diabetes receiving hemodialysis have impaired gait speed and balance compared to the general population, which have been associated with increased risks of falls and mortality. This study evaluated the effectiveness of a game-based intradialytic exercise training program (iExergame) on improving gait speed and balance. This was a single-blind randomized controlled trial. The intervention group (IG) received iExergame training using real-time audiovisual feedback with wearable inertial sensors. The control group (CG) received conventional training without any technology. Both trainings were intradialytic, non-weight-bearing, and used ankle range of motion. Gait and balance parameters were collected at baseline and 4-week follow-up. Data from 70 adults (age 64.2 ± 9.0 years) were analyzed. Compared to the CG, the IG showed greater changes between baseline and 4-week follow-up in several parameters. Gait parameters included faster speeds and longer stride lengths, particularly during dual task walking (p < 0.050). Balance parameters included reductions in center of mass (p = 0.004), ankle (p < 0.001), and hip (p = 0.010) sways during semi-tandem stance, particularly in users of assistive devices. iExergame training could improve gait speed and balance in this population and might be an option to increase intradialytic exercise adherence while reducing burdens of exercise administration.

"Off/On" Fluorescent Probe based on Aggregation-Induced Quenching of ZnO-Quantum dots for Determination of Ara-C: Pharmacokinetic Applications, Adsorption Kinetics & Green Profile Assessment.

Herein, a turn "Off/On" fluorescence probe based on ZnO quantum dots (ZnO-QDs) has been proposed and successfully utilized for the determination of Ara-C (cytarabine) using ceric ions (Ce4+) as quencher and ethylenediamine (ED) as a linker. The probe is based initially on the quenching effect of Ce4+ ions on the strong native fluorescence of ZnO-QDs forming the Turn Off system (Ce@ZnO-QDs) that believed to occur due to the aggregation-induced quenching (AIQ) mechanism. The second step is the addition of Ara-C in the presence of ethylenediamine (ED) that encourages the formation of Ara-C/ED/Ce4+ as well as the release of the free ZnO-QDs, leading to the recovery of the fluorescence intensity. The developed sensing platform shows a linear response towards Ara-C over the range of 10 to 1000 ng mL-1 giving a limit of detection (LOD) and limit of quantitation (LOQ) of 1.22 ng mL-1 and 3.70 ng mL-1, respectively. A dispersive magnetic solid phase micro-extraction (dMSPE) method was developed and optimized for the extraction of Ara-C in spiked human plasma using thiol-modified magnetite nanoparticles (S-MNPs). The proposed platform exhibits good sensitivity toward Ara-C in the presence of different interfering substances. Excellent recoveries are obtained after spiking different concentrations of Ara-C into rabbit plasma samples. The validated experimental parameters have been successfully applied to monitor the pharmacokinetic profile of Ara-C in rabbit plasma. A detailed adsorption kinetics study has been carried out to provide a deep insight into the adsorption behavior of Ara-C on the thiol-doped-magnetite nanoparticles. The greenness assessment of the proposed method was achieved and compared with other reported methods using two tools of greenness; the green analytical procedure index (GAPI) and the analytical greenness calculator AGREE.

Objective assessment of mobility among adults with diabetes and end-stage renal disease using walking aid: A cross-sectional cohort study.

BACKGROUND: This cross-sectional study aimed to compare physical activity levels, plantar sensation, and fear of falling between individuals with diabetes undergoing hemodialysis, with or without walking aids. METHODS: Sixty-four participants were recruited, with 37 not using walking aids (age = 65.8 ± 0.7 years, 46% female) and 27 using walking aids (age = 69.2 ± 1.2 years, 63% female). Physical activity was measured using validated pendant sensors over two consecutive days. Concern for falling and plantar numbness were assessed using the Falls Efficacy Scale-International and vibration perception threshold test, respectively. FINDINGS: Participants using walking aids exhibited a greater fear of falling (84% vs. 38%, p < 0.01) and fewer walking bouts (p < 0.01, d = 0.67) and stand-to-walk transitions (p < 0.01, d = 0.72) compared to those not using walking aids. The number of walking bouts was negatively correlated with concern for falling scores (ρ = -0.35, p = 0.034) and vibration perception threshold (R = -0.411, p = 0.012) among individuals not using walking aids. However, these correlations were not significant among those using the walking aid. There was no significant group difference in active behavior (walking + standing %) and sedentary behavior (sitting + lying %). INTERPRETATION: Those undergoing hemodialysis often lead sedentary lives, with mobility affected by fear of falling and plantar numbness. Using walking aids can help, but it doesn't guarantee more walking. A combined psychosocial and physical therapy approach is key for managing fall concerns and improving mobility.

Intradialytic plantar electrical nerve stimulation to improve mobility and plantar sensation among adults with diabetes undergoing hemodialysis: a randomized double-blind trial.

BACKGROUND: Impaired mobility is a debilitating consequence of hemodialysis. We examined the efficacy of intradialytic-plantar-electrical-nerve-stimulation (iPENS) to promote mobility among diabetes patients undergoing hemodialysis.. METHODS: Adults with diabetes undergoing hemodialysis received either 1-h active iPENS, (Intervention-Group) or non-functional iPENS (Control-Group) during routine hemodialysis for 12 weeks (3 sessions/week). Participants and care-providers were blinded. Mobility (assessed using a validated pendant-sensor) and neuropathy (quantified by vibration-perception-threshold test) outcomes were assessed at baseline and 12 weeks. RESULTS: Among 77 enrolled subjects (56.2 ± 2.6 years old), 39 were randomly assigned to the intervention group, while 38 were assigned to the control group. No study-related adverse events and dropouts were reported in the intervention group. Compared to the control group, significant improvements with medium to large effect sizes were observed in the intervention group at 12 weeks for mobility-performance metrics, including active-behavior, sedentary-behavior, daily step counts, and sit-to-stand duration variability (p < 0.05), Cohen's d effect size (d = 0.63-0.84). The magnitude of improvement in active-behavior was correlated with improvement in the vibration-perception-threshold test in the intervention group (r = - 0.33, p = 0.048). A subgroup with severe-neuropathy (vibration-perception-threshold > 25 V) showed a significant reduction in plantar numbness at 12 weeks compared to baseline (p = 0.03, d = 1.1). CONCLUSIONS: This study supports feasibility, acceptability, and effectiveness of iPENS to improve mobility and potentially reduce plantar numbness in people with diabetes undergoing hemodialysis. Considering that exercise programs are not widely used in hemodialysis clinical practice, iPENS may serve as a practical, alternative solution to reduce hemodialysis-acquired weakness and promote mobility.

Development and evaluation of a dual-purpose machine for chopping and crushing forage crops.

Reducing reliance on fossil fuels with clean and sustainable alternatives is essential for mitigating climate change and global warming-related environmental concerns. Previous researchers have studied the performance of choppers and crushers as separate units powered by diesel or gasoline engines. Nowadays, an increasing interest in producing Eco-friendly machines that stand out for being dual purposes, cost-effectiveness, and with lengths suitable for feeding ruminants are imperative to achieving economic and sustainable goals. Therefore, this study aims to solve these issues and gaps by developing and evaluating a dual-purpose forage machine for chopping and crushing operations to achieve both operations more efficiently and at a lower cost. The developed forage machine's performance was evaluated for chopping operation using maize stalks with four different rotational speeds of 1200, 1400, 1600, and 1800 rpm and four different moisture contents of 22.7, 43.3, 59.8, and 74.6% (w.b.). Also, the crushing operation was evaluated using maize ears with four different crusher speeds of 1200, 1400, 1600, and 1800 rpm and three different sieves with holes' diameters of 6, 8, and 10 mm. The results concluded that the highest efficiencies with values of 94.17 and 92.85% were obtained at 1800 rpm chopper rotational speed and 22.7% moisture content for the chopper and 1200 rpm crusher rotational speed and 10 mm sieve hole diameter for the crusher, respectively. At these proper operational parameters, the machine productivity of 2.44 and 0.31 ton.hr-1, the specific energy requirements of 3.22 and 4.50 kW h.ton-1, and the estimated production costs of 23.56 and 121.24 EGP.ton-1 (1.25 and 6.38 USD.ton-1) were obtained for chopper and crusher, respectively.

Pill-burden and its association with treatment burden among patients with advanced stages of chronic kidney disease.

Introduction: Chronic kidney disease (CKD) is associated with multimorbidity and high treatment burden. Pill-burden is one component of the overall treatment burden. However, little is known about its magnitude and contribution to the overall treatment burden among patients with advanced stages of CKD. This study aimed to quantify the magnitude of pill-burden in dialysis-dependent vs. non-dialysis-dependent advanced-stage CKD patients and its association with treatment burden. Methods: This was a cross-sectional study for the assessment of pill-burden and treatment burden among non-dialysis and hemodialysis (HD)-dependent CKD patients. Pill-burden was quantified as "number of pills/patient/week" through electronic medical record, while treatment burden was assessed using the "Treatment Burden Questionnaire (TBQ)". Furthermore, oral and parenteral medication burden was also quantified. Data were analyzed using both descriptive and inferential analysis, including Mann - Whitney U test and two-way between groups analysis of variance (ANOVA). Results: Among the 280 patients included in the analysis, the median (IQR) number of prescribed chronic medications was 12 (5.7) oral and 3 (2) parenteral medications. The median (IQR) pill-burden was 112 (55) pills/week. HD patients experienced higher pill-burden than non-dialysis patients [122 (61) vs. 109 (33) pills/week]; however, this difference did not reach statistical significance (p = 0.81). The most commonly prescribed oral medications were vitamin D (90.4%), sevelamer carbonate (65%), cinacalcet (67.5%), and statins (67.1%). Overall, patients who had high pill-burden (≥112 pills/week) had significantly higher perceived treatment burden compared to low pill-burden patients (<112 pills/week) [47(36.2) vs. 38.5(36.7); p = 0.0085]. However, two-way ANOVA showed that dialysis status is the significant contributor to the treatment-burden in the high overall pill-burden group (p < 0.01), the high oral-medication-burden group (p < 0.01), and the high parenteral-medication-burden group (p = 0.004). Conclusions: Patients with advanced CKD experienced a high pill-burden, which increases the treatment burden; however, the dialysis status of the patient is the main factor affecting the overall treatment burden. Future intervention studies should target this population with an aim to reduce polypharmacy, pill-burden, and treatment burden, which may ultimately improve CKD patients' quality of life.

Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple "omics" assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.

Investigating miRNA-related Pathways Contributing to Kidney Cancer Pathogenesis.

BACKGROUND/AIM: Renal cell carcinoma is one of the most common types of cancer worldwide. Understanding tumor pathogenesis is important in developing better treatment. Micro RNAs (miRNAs) are key players in controlling cancer behavior. Transcription factors (TFs) are potentially responsible for controlling miRNA expression and dysregulation in kidney cancer. The objective of this study was to better understand the TF-miRNA axis of interaction. MATERIALS AND METHODS: We utilized publicly available databases to investigate miRNA-TF interactions, including ChipBase database for TFs that binds to the promoters of miRNAs which are dysregulated in renal cell carcinoma. Renal cancer-specific TFs were extracted from the list using the GENT Database. We assessed the prognostic significance of these TFs using cBioPortal. RESULTS: We identified TFs which bind to miRNA promoters, including hepatocyte nuclear factor-4 alpha (HNF-4α), E2F transcription factor 4 (E2F4), signal transducer and activator of transcription 1 (STAT1), Sp1 transcription factor (SP1), GATA binding protein 6 (GATA6), and nuclear factor kappa B (NFκB). These TFs were positively correlated with their targeted miRNAs, including miR-200c, miR-15a, miR-146b, miR-155, and miR-223. We recognized unique patterns of interactions, including a divergent effect in which multiple miRNAs are simultaneously affected by the same TF. CONCLUSION: Our results show that miRNA-TF interaction is complex. Expression levels of these TFs were found to correlate with renal carcinoma prognosis and have potential utility as biomarkers for aggressive tumor behavior. Targeting these TFs may result in modulating the expression of their target genes and miRNAs, with subsequent therapeutic implications.

Biological elimination of a high concentration of hydrogen sulfide from landfill biogas.

Hydrogen sulfide (H2S) is one of the main contaminants found in biogas, which is one of the end products of the anaerobic biodegradation of proteins and other sulfur-containing compounds in solid waste. The presence of H2S is one of the factors limiting the valorization of biogas. To valorize biogas, H2S must be removed. This study evaluated the performance of a pilot-scale biotrickling filter system on H2S removal from landfill biogas. The biotrickling filter system, which was packed with stainless-steel pall rings and inoculated with an H2S-oxidizing consortium, was designed to process 1 SCFM of biogas, which corresponds to an empty bed residence time (EBRT) of 3.9 min and was used to determine the removal efficiency of a high concentration of hydrogen sulfide from landfill biogas. The biofiltration system consisted of two biotrickling filters connected in series. Results indicate that the biofiltration system reduced H2S concentration by 94 to 98% without reducing the methane concentration in the outlet biogas. The inlet concentration of hydrogen sulfide, supplied to the two-phase bioreactor, was in the range of 900 to 1500 ppmv, and the air flow rate was 0.1 CFM. The EBRTs of the two biotrickling filters were 3.9 and 0.9 min, respectively. Approximately 50 ± 15.7 ppmv of H2S gas was detected in the outlet gas. The maximum elimination capacity of the biotrickling filter system was found to be 24 g H2S·m-3·h-1, and the removal efficiency was 94 ± 4.4%. During the biological process, the performance of the biotrickling filter was not affected when the pH of the recirculated liquid decreased to 2-3. The overall performance of the biotrickling filter system was described using a modified Michaelis-Menten equation, and the Ks and Vm values for the biosystem were 34.7 ppmv and 20 g H2S·m-3·h-1, respectively.

Protein and peptide delivery to lungs by using advanced targeted drug delivery.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

Effectiveness of Messenger RNA Vaccines against SARS-CoV-2 Infection in Hemodialysis Patients: A Case-Control Study.

Patients with end-stage kidney disease (ESKD) are at increased risk for SARS-CoV-2 infection and its complications compared with the general population. Several studies evaluated the effectiveness of COVID-19 vaccines in the dialysis population but showed mixed results. The aim of this study was to determine the effectiveness of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection in hemodialysis (HD) patients in the State of Qatar. We included all adult ESKD patients on chronic HD who had at least one SARS-CoV-2 PCR test done after the introduction of the COVID-19 mRNA vaccines on 24 December 2020. Vaccinated patients who were only tested before receiving any dose of their COVID-19 vaccine or within 14 days after receiving the first vaccine dose were excluded from the study. We used a test-negative case−control design to determine the effectiveness of the COVID-19 vaccination. Sixty-eight patients had positive SARS-CoV-2 PCR tests (cases), while 714 patients had negative tests (controls). Ninety-one percent of patients received the COVID-19 mRNA vaccine. Compared with the controls, the cases were more likely to be older (62 ± 14 vs. 57 ± 15, p = 0.02), on dialysis for more than one year (84% vs. 72%, p = 0.03), unvaccinated (46% vs. 5%, p < 0.0001), and symptomatic (54% vs. 21%, p < 0.0001). The effectiveness of receiving two doses of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection was 94.7% (95% CI: 89.9−97.2) in our HD population. The findings of this study support the importance of using the COVID-19 mRNA vaccine in chronic HD patients to prevent SARS-CoV-2 infection in such a high-risk population.

Effects of novel anemia nurse manager program on hemodialysis: a retrospective study from Qatar.

INTRODUCTION: Anemia management in dialysis is challenging. Keeping hemoglobin levels within a tight range is difficult. A new program (anemia nurse manager [ANM]) was started for better anemia management. This study aimed to compare traditional anemia management with the new ANM model regarding the achievement of better hemoglobin targets (range, 10-12 g/dL), avoidance of extreme hemoglobin levels ( < 9 or >13 g/dL), and evaluation of the cost-effectiveness of the new model. METHODS: This retrospective observational study compared traditional anemia management with management involving our new ANM model. Patients on hemodialysis in all ambulatory dialysis clinics in Qatar were included. The study included three phases: phase 1 (observation): June 2015 to August 2015, 460 patients; phase 2 (pilot): September 2015 to May 2016, 211 patients; and phase 3 (expansion in two phases): June 2016 to February 2017 and October 2017 to June 2018, 610 patients. Hemoglobin, iron saturation, and ferritin were evaluated according to the protocol. RESULTS: In this study, 55% of the patients achieved the target hemoglobin in phase 1 compared with 75% in phase 2 (p = 0.0007). The hemoglobin level within the target range was sustained at 72% ± 5% of patients in phase 3. The achievement rate of the target hemoglobin level increased from 56% (May 2015) to 72% (July 2018) (p < 0.001). The proportion of patients with extreme hemoglobin declined from 10.7% in phase 1 to 6.4% in phase 2 and sustained at 8% afterward. Reducing the doses of erythropoietin stimulating agents, owing to the use of the ANM model, saved costs by approximately 11%. CONCLUSIONS: The ANM model was able to achieve and maintain hemoglobin levels within the target range and decrease extreme hemoglobin levels. These outcomes improved patient care by avoiding high hemoglobin (increase thrombosis, cancer recurrence, stroke, and death) and low hemoglobin (weakness, poor quality of life, and need for transfusion) levels. The ANM model was cost effective even after including the salaries of nurses. This model can be considered in other aspects of patient care in dialysis.

Mortality and associated risk factors of COVID-19 infection in dialysis patients in Qatar: A nationwide cohort study.

CONTEXT: Patients on maintenance dialysis are more susceptible to COVID-19 and its severe form. We studied the mortality and associated risks of COVID-19 infection in dialysis patients in the state of Qatar. METHODS: This was an observational, analytical, retrospective, nationwide study. We included all adult patients on maintenance dialysis therapy who tested positive for COVID-19 (PCR assay of the nasopharyngeal swab) during the period from February 1, 2020, to July 19, 2020. Our primary outcome was to study the mortality of COVID-19 in dialysis patients in Qatar and risk factors associated with it. Our secondary objectives were to study incidence and severity of COVID-19 in dialysis patients and comparing outcomes between hemodialysis and peritoneal dialysis patients. Patient demographics and clinical features were collected from a national electronic medical record. Univariate Cox regression analysis was performed to evaluate potential risk factors for mortality in our cohort. RESULTS: 76 out of 1064 dialysis patients were diagnosed with COVID-19 (age 56±13.6, 56 hemodialysis and 20 peritoneal dialysis, 56 males). During the study period, 7.1% of all dialysis patients contracted COVID-19. Male dialysis patients had double the incidence of COVID-19 than females (9% versus 4.5% respectively; p<0.01). The most common symptoms on presentation were fever (57.9%), cough (56.6%), and shortness of breath (25%). Pneumonia was diagnosed in 72% of dialysis patients with COVID-19. High severity manifested as 25% of patients requiring admission to the intensive care unit, 18.4% had ARDS, 17.1% required mechanical ventilation, and 14.5% required inotropes. The mean length of hospital stay was 19.2 ± -12 days. Mortality due to COVID-19 among our dialysis cohort was 15%. Univariate Cox regression analysis for risk factors associated with COVID-19-related death in dialysis patients showed significant increases in risks with age (OR 1.077, CI 95%(1.018-1.139), p = 0.01), CHF and COPD (both same OR 8.974, CI 95% (1.039-77.5), p = 0.046), history of DVT (OR 5.762, CI 95% (1.227-27.057), p = 0.026), Atrial fibrillation (OR 7.285, CI 95%(2.029-26.150), p = 0.002), hypoxia (OR: 16.6; CI 95%(3.574-77.715), p = <0.001), ICU admission (HR30.8, CI 95% (3.9-241.2), p = 0.001), Mechanical ventilation (HR 50.07 CI 95% (6.4-391.2)), p<0.001) and using inotropes(HR 19.17, CI 95% (11.57-718.5), p<0.001). In a multivariate analysis, only ICU admission was found to be significantly associated with death [OR = 32.8 (3.5-305.4), p = 0.002)]. CONCLUSION: This is the first study to be conducted at a national level in Qatar exploring COVID-19 in a dialysis population. Dialysis patients had a high incidence of COVID-19 infection and related mortality compared to previous reports of the general population in the state of Qatar (7.1% versus 4% and 15% versus 0.15% respectively). We also observed a strong association between death related to COVID-19 infection in dialysis patients and admission to ICU.

Prevalence of Depression and Sleep Disorders in Patients on Dialysis: A Cross-Sectional Study in Qatar.

Patients with end-stage renal disease treated with dialysis have poor quality of life (QOL). Improving QOL in these patients with multiple comorbidities is a large challenge. We performed a cross-sectional study to evaluate the prevalence and associated factors of depression and sleep disorders in this population. Our primary aim was to evaluate QOL measures in dialysis patients in Qatar through a series of validated questionnaires mainly concerning depression and sleep disorders. Our secondary aim was to study the associations of age, sex, and comorbid conditions with the QOL measures. We hypothesized that end-stage renal disease (ESRD) patients on dialysis would have disturbed QOL due to both ESRD and dialysis and comorbidities. This prospective cross-sectional study included adult ESRD patients receiving either hemodialysis (HD) or peritoneal dialysis (PD) in the main tertiary dialysis unit in Qatar. We administered two surveys to evaluate depression (the Center for Epidemiologic Studies Depression Scale, http://www.bmedreport.com/archives/7139) and sleep disorders (the Pittsburgh Sleep Quality Index, https://www.sleep.pitt.edu/instruments/). We also reviewed patient demographics, comorbidities, and laboratory test results to evaluate any associated factors. We randomly studied 253 patients (62% on HD and 38% on PD). Overall, 48% of patients had depression, while 83.8% had sleep disorders. The PD had more poor sleepers than the HD group (89.1% versus (vs.) 75%, p=0.003). Most of our dialysis patients had poor sleep, but it was more significant in the elderly group 109 (90%) than in the young group 103 (78%) (p=0.009). Patients with diabetes mellitus (DM) had significantly more prevalence of poor sleep (131 (88.5%)) than those without DM (81 (77.1%), p=0.01). More female patients had depression than male patients (52% vs. 25%, p < 0.0001; odds ratio: 3.27 (95% confidence interval: 1.9-5.6), p < 0.0001). This is the first study in Qatar to evaluate depression and sleep disorders in patients on dialysis therapy.