Correlation between socio-demographic characteristics, metabolic control factors and personality traits with self-perceived health status in patients with diabetes: A cross-sectional study.

Purpose: This study aimed to assess the relationship between metabolic control factors, socio-demographic characteristics, personality traits, and self-perceived health status in diabetes. Methods: This cross-sectional study included 318 patients with type 1 and 2 diabetes (DM). Participants completed a questionnaire-based survey, which included the NEO Personality Inventory-Revised to measure five personality dimensions and the SF-12 survey to assess self-perceived health status. Binary logistic regression was performed to analyze the data, with socio-demographic characteristics, clinical data, and nutrition status as independent variables, and self-perceived health status (categorized as poor or good condition) as the dependent variable. Unadjusted and adjusted binary logistic regression analyses were used to examine the association between personality traits (high vs. low) and metabolic control factors (good control vs. bad control) with health status scores. Results: 60.7% of the participants with diabetes in the study described their health as "good." The results indicated that female gender (OR: 0.314, 95%CI: 0.105-0.938, P = 0.038), age > 60 years (OR: 0.263, 95%CI: 0.117-0.592, P = 0.001), comorbidities (OR: 0.314, 95%CI: 0.178-0.556, P = 0.001), DM complications (OR: 0.531, 95%CI: 0.337-0.838, P = 0.007), diabetic neuropathy (OR: 0.562, 95%CI: 0.356-0.886, P = 0.013), and diabetic ulcer (OR: 0.130, 95%CI: 0.023-0.747, P = 0.022) were independent variables associated with a "poor" health status. However, regular physical activity (OR: 3.144, 95%CI: 1.209-8.175, P = 0.019) and a healthy nutritional diet (OR: 2.456, 95%CI: 1.421-4.245, P < 0.001) were associated with a higher likelihood of a "good" self-perceived health status. Conclusion: Preventive programs and interventions aimed at improving self-perceived health among patients with diabetes should focus on increasing regular physical activity and promoting a healthy nutritional status. These actions should be particularly targeted towards female and older patients with higher neuroticism traits.

Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial.

OBJECTIVES: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. METHODS: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. RESULTS: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). CONCLUSIONS: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. CLINICAL TRIAL REGISTRATION: www.IRCT.irIRCT20171122037571N1.

Tacrolimus-induced cholestatic hepatotoxicity after renal transplantation: a case report.

BACKGROUND: In this manuscript, we report a case of tacrolimus-associated hepatotoxicity in a kidney transplant recipient. CASE PRESENTATION: In this case report, a 56 years old Arab male patient who received a kidney transplant presented with icterus, weakness, and lethargy two weeks after transplantation and tacrolimus initiation. In laboratory analysis hyperbilirubinemia and a rise in hepatic enzymes were observed. All possible causes of hepatotoxicity were examined. The panel for infectious causes was negative. Drug-induced liver injury was diagnosed. The patient's immunosuppressive regimen was changed to a cyclosporine-based regimen and after this change bilirubin and hepatic enzymes decreased and the patient was discharged without signs and symptoms of hepatitis. CONCLUSION: It seems that the patient's hyperbilirubinemia was due to tacrolimus, and the patient's bilirubin decreased after stopping tacrolimus.

A 39 Year mortality study of survivors exposed to sulfur mustard agent: A survival analysis.

Background: The primary objective of this study was to analyze the long-term survival of 48,067 chemical warfare survivors who suffered from pulmonary, cutaneous, and ocular lesions in the decades following the Iran-Iraq war. Methods: The data for this study were obtained from the Veterans and Martyr Affair Foundation (VMAF) database. The survivors were divided into two groups based on whether they were evacuated/admitted (EA) to a hospital or not evacuated/admitted (NEA) to a hospital. The proportional hazard (PH) assumption for age categories, gender, exposure statuses, and eye severity was not satisfied. Therefore, we used a Generalized Gamma (GG) distribution with an Accelerated Failure Time (AFT) model for analysis. Results: The study included a total of 48,067 observations, and among them, 4342 (9.03 %) died during the study period. The mean (SD) age of the survivors was 55.99 (7.9) years. The mortality rate increased with age, and higher rates were observed in males. Survival probabilities differed significantly among age categories, provinces, lung severity, and eye severity based on log-rank tests (p-value<0.05 for all). The GG model results showed that higher age and being male were associated with a shorter time to death. The study also found that the mortality rate was significantly higher in the EA group compared to the NEA group. Conclusion: The present study showed no significant difference in survival time between the EA and NEA groups. The findings suggest that pulmonary lesions caused by mustard gas are more likely to be fatal compared to skin and eye lesions. The results also indicate a potential association between survival time and the severity of lung damage.

Sinopharm (HB02)-associated vaccine-induced immune thrombotic thrombocytopenia: a case report.

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia is associated with the coronavirus disease 2019 vaccines. It has been reported by vector-based vaccines. To the best of our knowledge, there is no report about vaccine-induced thrombotic thrombocytopenia in whole-virus vaccines. We are presenting the first case of vaccine-induced thrombotic thrombocytopenia with this type of vaccine. CASE PRESENTATION: An 18-year-old male Caucasian patient with complaints of severe abdominal, low back, and lower extremity pain presented to the medical center. He received the first dose of the Sinopharm (HB02) vaccine against coronavirus disease 2019 10 days before hospital attendance. In the laboratory examination, decreased platelet count and increased D-dimer were observed. During hospital admission, the diagnosis of pulmonary embolism was reached. He received vaccine-induced thrombotic thrombocytopenia therapy consisting of intravenous immune globulin and direct oral anticoagulant. Platelet count increased and he was discharged after 1 month. CONCLUSION: This case highlights the possibility of vaccine-induced thrombotic thrombocytopenia occurrence by whole-virus coronavirus disease 2019 vaccines. Compared with vector-based vaccines, this phenomenon is rare for whole-virus vaccines. More studies on this type of vaccine regarding thrombotic thrombocytopenia should be considered.

Assessment of drought conditions and prediction by machine learning algorithms using Standardized Precipitation Index and Standardized Water-Level Index (case study: Yazd province, Iran).

Drought as a natural phenomenon has always been a serious threat to regions with hot and dry climates. One of the major effects of drought is the drop in groundwater level. This paper focused on the SPI (Standardized Precipitation Index) and SWI (Standardized Water-Level Index) to assess meteorological and hydrological drought, respectively. In the first part, we used different time frames of SPI (3, 6, 12, and 24 months) to investigate drought in Yazd, a dry province in the center of Iran for 29 years (1990-2018). Then, in the second part, the relationship between SPI and SWI was investigated in the three aquifers of Yazd by some rain gauge stations and the closest observation wells to them. In addition to using SPI and SWI, we also used different machine learning (ML) algorithms to predict drought conditions including linear model and six non-linear models of K_Nearest_Neighbors, Gradient_Boosting, Decision_Tree, XGBoost, Random_Forest, and Neural_Net. To evaluate the accuracy of the mentioned models, three statistical indicators including Score, RMSE, and MAE were used. Based on the results of the first part, Yazd province has changed from mild wet to mild drought in terms of meteorological drought (the amount of rainfall according to SPI), and this condition can worsen due to climate change. The models used in ML showed that SPI-6 (score ave = 0.977), SPI-3 (score ave = 0.936), SPI-24 (score ave = 0.571), and SPI-12 (score ave = 0.413) indices had the highest accuracy, respectively. The models of Neural_Net (score ave = 0.964-RMSE ave = 0.020-MAE ave = 0.077) and Gradient_Boosting (score ave = 0.551-RMSE ave = 0.124-MAE ave = 0.248) had the highest and lowest accuracy in prediction of the SPI in all four-time scales. Based on the results of the second part, about the SWI, Random_Forest model (score = 0.929-RMSE = 0.052-MAE = 0.150) and model of Neural_Net (score = 0.755-RMSE = 0.235-MAE = 0.456) had the highest and lowest accuracy, respectively. Also, hydrological drought (reduction of the groundwater level) of the region has been much more severe, and according to the low correlation coefficient of average SPI and SWI (R2 = 0.14), we found that the uncontrolled pumping wells, as a main factor than a shortage of rainfall, have aggravated the hydrological drought, and this region is at risk of becoming a more arid region in the future.

Design and Fabrication of a High Performance Microfluidic Chip for Blood Plasma Separation: Modelling and Prediction of System Behaviour via CFD Method.

This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick's law of diffusion was validated for this diffusion transfer, the Navier-Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.

Microparticle separation using dielectrophoresis-assisted inertial microfluidics: A GPU-accelerated immersed boundary-lattice Boltzmann simulation.

In this study, the migration of microparticles towards the inertial equilibrium positions in a straight microchannel with a square cross section in the presence of an inhomogeneous oscillating electric field was examined. The dynamics of microparticles were simulated using the immersed boundary-lattice Boltzmann method of fluid-structure interaction simulation. Moreover, the lattice Boltzmann Poisson solver was applied to calculate the electric field required for calculation of the dielectrophoretic force using the equivalent dipole moment approximation. These numerical methods were implemented on a single GPU coupled with the AA pattern of storing distribution functions in memory to speed up the computationally demanding simulation of microparticles dynamics. In the absence of an electric field, spherical polystyrene microparticles migrate to four symmetric stable equilibrium positions corresponding to the sidewalls of the square cross-sectional microchannel. The equilibrium distance from the sidewall was increased by increasing the particle size. The equilibrium positions near electrodes disappeared and particles migrated to the other equilibrium positions far from the electrodes by the application of the high-frequency oscillatory electric field at voltages beyond a threshold value. Finally, a two-step dielectrophoresis-assisted inertial microfluidics methodology was introduced for particle separation based on the crossover frequencies and the observed threshold voltages of different particles. The proposed method exploited the synergistic effect of dielectrophoresis and inertial microfluidics methods to remove their limitations, allowing the separation of a broad range of polydisperse particle mixtures with a single device in a short time.

Analytical chromatography approaches during the synthesis and conjugation of methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) to epoetin beta.

Conjugation of epoetin beta (EPO) with methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) was studied. The compound mPEG-SBA was synthesized from mPEG, and the obtained intermediates and final product were analyzed by a reversed-phase chromatographic system equipped with an evaporative light scattering detector. Labeling the hydroxyl group in PEGs with benzoyl chloride and succinimide with benzylamine was applied to resolve and characterize different PEGs. The synthesized mPEG-SBA was used for the PEGylation of EPO. A size-exclusion chromatographic method monitored the reaction, simultaneously determining the PEGylated and unreacted EPO and protein aggregates. A borate buffer (0.1 M, pH 7.8) and PEG/protein molar ratio of 3:1 produced a maximum amount of monoPEGylated EPO with the minimum amount of polyPEGylated EPO variants. Although EPO is considered a stable glycoprotein hormone that remains monomeric when refrigerated, PEGylation of EPO with mPEG-SBA resulted in the significant formation of EPO dimer. The formation of EPO dimer and polyPEGylated EPO was pH-dependent, showing higher amounts of aggregates and lower amounts of polyPEGylated forms in lower pH values. Accordingly, aggregated EPO should be considered a major PEGylation-related impurity. In conclusion, the present study highlighted the importance of having suitable analytical approaches in controlling mPEG-SBA synthesis and conjugation to EPO.

Clinical outcomes of kidney recipients with COVID-19 (COVID-19 in kidney recipients).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality since late 2019. Patients undergoing kidney transplantation (KT) are prone to COVID-19 due to immunosuppressive drug use and various comorbidities such as hypertension and diabetes. METHODS: One hundred thirty-three KT recipients with COVID-19 were included in this retrospective cohort study. Hospital mortality was considered a primary outcome, while acute kidney injury (AKI) was considered a secondary outcome. Demographic information, maintenance immunosuppression, medical history, laboratory information, and echocardiographic and electrocardiography results of patients were recorded. Patients were also followed for 2 months post-discharge for post-COVID-19 symptoms, readmission, and transplant function. RESULTS: Regarding the primary outcome of the 133 patients, 13 died and 120 survived. The deceased patients were significantly older (median age, 64 vs. 50.5 years; p = 0.04) and had a significantly higher median serum creatinine level (p = 0.002) and lower median glomerular filtration rate (p = 0.010) than patients who survived. The incidence of AKI was 47.3%, more common in deceased patients (p = 0.038) than in patients who survived. Troponin levels were significantly higher in deceased patients and those with AKI (p = 0.0004 and p = 0.039, respectively) than in patients who survived and those without AKI. A multivariable Cox regression analysis revealed that older age (adjusted hazard ratio, 1.13; 95% confidence interval, 1.01-1.27) and AKI (adjusted hazard ratio, 3.43; 95% confidence interval, 1.34-8.79) were associated with in-hospital mortality. CONCLUSION: In conclusion, kidney recipients with COVID-19 had a higher mortality rate than the general population, with a higher prevalence in older individuals and those who experienced AKI during hospitalization than in patients who survived and those without AKI.

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. METHODS: The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. RESULTS: There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. CONCLUSION: Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Opening Pandora's Box: Neglected Biochemical Potential of Permafrost-Associated Fungal Communities in a Warming Climate.

Permafrost, a vast storage reservoir of frozen organic matter, is rapidly thawing due to climate change, releasing previously preserved carbon into the environment. This phenomenon has significant consequences for microbial communities, including fungi, inhabiting permafrost-associated regions. In this review, we delve into the intricate interplay between permafrost thawing and fungal diversity and functionality with an emphasis on thermokarst lakes. We explore how the release of organic carbon from thawing permafrost alters the composition and activities of fungal communities, emphasizing the potential for shifts in taxonomic diversity and functional gene expression. We discuss the formation of thermokarst lakes, as an example of permafrost thaw-induced ecological disruptions and their impact on fungal communities. Furthermore, we analyze the repercussions of these changes, including effects on nutrient cycling, plant productivity, and greenhouse gas (GHG) emissions. By elucidating the multifaceted relationship between permafrost thaw and aquatic fungi, this review provides valuable insights into the ecological consequences of ongoing climate change in permafrost-affected regions.

Hyperglycemia screening based on survey data: an international instrument based on WHO STEPs dataset.

BACKGROUND: Hyperglycemia is rising globally and its associated complications impose heavy health and economic burden on the countries. Developing effective survey-based screening tools for hyperglycemia using reliable surveillance data, such as the WHO STEPs surveys, would be of great importance in early detection and/or prevention of hyperglycemia, especially in low or middle-income regions. METHODS: In this study, data from the nationwide 2016 STEPs study in Iran were used to identify socioeconomic, lifestyle, and metabolic factors associated with hyperglycemia. Furthermore, the ability of five commonly used machine learning algorithms (random forest; gradient boosting; support vector machine; logistic regression; artificial neural network) in the prediction of hyperglycemia on STEPs dataset were compared via tenfold cross validation in terms of specificity, sensitivity, and the area under the receiver operating characteristic curve. RESULTS: A total of 17,705 individuals were included in this study, of those 29.624% (n = 5245) had (undiagnosed) hyperglycemia. Multivariate logistic regression analysis showed that older age (for the elderly group: OR = 5.096; for the middle-aged group: OR = 2.784), high BMI status (morbidly obese: OR = 3.465; obese: OR = 1.992), having hypertension (OR = 1.647), consuming fish more than twice per week (OR = 1.496), and abdominal obesity (OR = 1.464) were the five most important risk factors for hyperglycemia. Furthermore, all the five hyperglycemia prediction models achieved AUC around 0.70, and logistic regression (specificity = 70.22%; sensitivity = 70.2%) and random forest (specificity = 70.75%; sensitivity = 69.78%) had the optimal performance. CONCLUSIONS: This study shows that it is possible to develop survey-based screening tools for early detection of hyperglycemia using data from nationwide surveys, such as WHO STEPs surveys, and machine learning techniques, such as random forest and logistic regression, without using blood tests. Such screening tools can potentially improve hyperglycemia control, especially in low or middle-income countries.

Comparing the Characteristics of Mucormycosis Between Cases with and without COVID-19; a Cross-sectional Study.

Introduction: Mucormycosis as a rare but life-threatening disease with 46-96% mortality, which challenged the healthcare system during the COVID-19 pandemic. This study aimed to compare the characteristics of mucormycosis between cases with and without COVID-19. Methods: This cross-sectional study was done in two referral hospitals, Imam Hossein and Labbafinezhad Hospitals, Tehran, Iran, between 21 March to 21 December 2021. Data related to all hospitalized adults subject with the diagnosis of mucormycosis during the study period was collected from patients' profiles and they were divided into two groups of with and without COVID-19 based on the results of real time PCR. Then demographic, clinical, and laboratory findings as well as outcomes were compared between the two groups. Results: 64 patients with the mean age of 53.40±10.32 (range: 33-74) years were studied (53.1% male). Forty-three (67.2%) out of the 64 subjects had a positive COVID-19 PCR test. The two groups had significant differences regarding some symptoms (cough (p < 0.001), shortness of breath (p = 0.006)), acute presentation (p = 0.027), using immunosuppressive (p = 0.013), using corticosteroid (p < 0.001), and outcomes (mortality (p = 0.018), need for intubation (p < 0.001)). 22 (34.3%) patients expired during hospital admission. Univariate analysis showed the association of in-hospital mortality with need for ventilation (p < 0.001), sinus involvement (p = 0.040), recent use of dexamethasone (p = 0.011), confirmed COVID-19 disease (p = 0.025), mean body mass index (BMI) (p =0.035), hemoglobin A1c (HbA1c) (p = 0.022), and median of blood urea nitrogen (BUN) (p =0.034). Based on the multivariate model, confirmed COVID-19 disease (OR = 5.01; 95% CI: 1.14-22.00; p = 0.033) and recent use of dexamethasone (OR= 4.08, 95% CI: 1.05-15.84, p = 0.042) were independent predictors of mortality in this series. Conclusion: The mucormycosis cases with concomitant COVID-19 disease had higher frequency of cough and shortness of breath, higher frequency of acute presentation, higher need for immunosuppressive, corticosteroid, and ventilator support, and higher mortality rate. The two groups were the same regarding age, gender, BMI, risk factors, underlying diseases, symptoms, and sites of involvement.

Mortality rate of people exposed to Mustard Gas during Iran-Iraq war in Sardasht, Iran: a 32 years retrospective cohort study.

BACKGROUND: Mustard gas (MG) is one of the most widely used chemical weapons in the past century. However, little information exists concerning long-term mortality from MG exposure. In this study, we investigated mortality rate among civilian people exposed to MG during Iran-Iraq war in Sardasht in Iran after 32 years.  METHODS: In this retrospective cohort study, data of people exposed to MG in Sardasht in 1987 were extracted from the Veterans and Martyr Affair Foundation of Iran up to March 20, 2019. Mortality rate, cumulative mortality and standardized mortality ratio with 95% confidence interval were calculated to explain mortality in the cohort, and then compared with general Iranian population. Cox regression analysis was used to indicate factor affecting the risk of death in the cohort.  RESULTS: Out of 1,203 exposed people at the beginning of the period, 148 people died by the end of the study, with an average age of 66.42 at the time of death. Total person-years of the people up to end of the study were 38,198.63 and mortality rate was equal to 387 per 100,000 persons-years. Total number of observed deaths was less than expected death and the all-cause standardized mortality ratio (SMR) was determined as 0.680 (95% CI: 0.574 - 0.798). Cause-specific SMR showed that observed death due to respiratory diseases was higher than expected (SMR: 1.75) (95% CI: 1.145 - 2.569). The results of univariate and multivariate cox regression analysis showed that increasing age and having severe late complications in lung were associated with increased risk of death among people in the cohort. CONCLUSION: In general, this result indicated that acute exposure to MG, even without wearing protective clothing and masks, could not increase all-cause mortality after 32 years if accompanied by special and ongoing care for those exposed.

Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis.

We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.

Using a Model-based Material Sparing Approach for Formulation and Process Development of a Roller Compacted Drug Product.

The present work details a material sparing approach that combines material profiling with Instron uniaxial die-punch tester and use of a roller compaction mathematical model to guide both formulation and process development of a roller-compacted drug product. True density, compression profiling, and frictional properties of the pre-blend powders are used as inputs for the predictive roller compaction model, while flow properties, particle size distribution, and assay uniformity of roller compaction granules are used to select formulation composition and ribbon solid fraction. Using less than 10 g of a model drug compound for material profiling, roller compacted blend in capsule formulations with appropriate excipient ratios were developed at both 1.4% and 14.4% drug loadings. Subsequently, scale-up batches were successfully manufactured based on the roller compaction process parameters obtained from predictive modeling. The measured solid fractions of roller compaction ribbon samples from the scale-up batches were in good agreement with the target solid fraction of the modeling. This approach demonstrated considerable advantages through savings in both materials and number of batches in the development of a roller-compacted drug product, which is of particular value at early development stages when drug substance is often limited and timelines are aggressive.

A Single-Centered Cohort Study on Favipiravir Safety and Efficacy in Pediatric Patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19) affects the pediatric population. Objectives: Due to limited data, this study aimed to evaluate the safety and efficacy of favipiravir in the hospitalized pediatric population diagnosed with COVID-19. Methods: The present retrospective cohort study was conducted on pediatric patients aged 1 - 18 years with a diagnosis of COVID-19 admitted to Mofid Children's Hospital, Tehran, Iran. Favipiravir was administrated at a dose of 60 mg/kg/day (max: 3200 mg/day) on the first day and then 23 mg/kg/day (max: 1200 mg/day) for 7 to 14 days. The patients were evaluated regarding the need for invasive mechanical ventilation, intensive care unit admission, duration of hospital stay, and mortality. Safety was measured by the occurrence of related adverse drug reactions (ADRs). Results: A total of 95 patients were included in the study. Favipiravir was administered to 25 patients. The need for invasive mechanical ventilation was reported in 4 (16.00%) and 11 (15.71%) patients in the favipiravir and control groups, respectively (P = 1.000). The median duration of hospital stays was significantly higher in patients who received favipiravir than in the controls (P = 0.002). No difference was observed in the mortality rate (P = 0.695). The ADRs, including decreased appetite, hypotension, and chest pain, were more prevalent in patients who received favipiravir than in the controls (P < 0.05). Conclusions: The administration of favipiravir in the pediatric population is associated with higher ADR occurrence with no positive effect on the need for invasive mechanical ventilation, hospital stay, and mortality. Further randomized controlled trials are necessary for better judgment.

Mental disorders pattern in staff of a military unit in Iran: the role of metabolic syndrome on latent class membership.

INTRODUCTION: Mental disorders are among the most prevalent health problems of the adult population in the world. This study aimed to identify the subgroups of staff based on mental disorders and assess the independent role of metabolic syndrome (MetS) on the membership of participants in each latent class. METHODS: This cross-sectional study was conducted among 694 staff of a military unit in Tehran in 2017. All staff of this military unit was invited to participate in this study. The collected data included demographic characteristics, anthropometric measures, blood pressure, biochemical parameters, and mental disorders. We performed latent class analysis using a procedure for latent class analysis (PROC LCA) in SAS to identify class membership of mental disorders using Symptom Checklist-90. RESULTS: Three latent classes were identified as healthy (92.7%), mild (4.9%), and severe (2.4%) mental disorders. Having higher age significantly decreased the odds of belonging to the mild class (adjusted OR (aOR = 0.21; 95% confidence interval (CI): 0.05-0.83) compared to the healthy class. Also, obesity decreased the odds of membership in mild class (aOR = 0.10, 95% CI: 0.01-0.92) compared to healthy class. On the other hand, being female increased the odds of being in severe class (aOR = 9.76; 95% CI: 1.35-70.65) class in comparison to healthy class. CONCLUSION: This study revealed that 7.3% of staff fell under mild and severe classes. Considering educational workshops in the workplace about mental disorders could be effective in enhancing staff's knowledge of these disorders. Also, treatment of comorbid mental disorders may help reduce their prevalence and comorbidity.

Promising effects of atorvastatin on mortality and need for mechanical ventilation in patients with severe COVID-19; a retrospective cohort study.

PURPOSE: Considering the anti-inflammatory effect of atorvastatin and the role of medical comorbidities such as hypertension and coronary artery disease on the prognosis of the COVID-19 patients, we aimed to assess the effect of atorvastatin add-on therapy on mortality caused by COVID-19. METHODS: We conducted a retrospective cohort study, including patients who were hospitalised with confirmed diagnosis of severe COVID-19. Baseline characteristics and related clinical data of patients were recorded. Clinical outcomes consist of in-hospital mortality, need for invasive mechanical ventilation and hospital length of stay. COX regression analysis models were used to assess the association of independent factors to outcomes. RESULTS: Atorvastatin was administered for 421 of 991 patients. The mean age was 61.640 ± 17.003 years. Older age, higher prevalence of hypertension and coronary artery disease reported in patients who received atorvastatin. These patients have shorter hospital length of stay (P = .001). Based on COX proportional hazard model, in-hospital use of atorvastatin was associated with decrease in mortality (HR = 0.679, P = .005) and lower need for invasive mechanical ventilation (HR = 0.602, P = .014). CONCLUSIONS: Atorvastatin add-on therapy in patient with severe COVID-19 was associated with lower in-hospital mortality and reduced the risk of need for invasive mechanical ventilation which supports to continue the prescription of the medication.