Immunogenicity of Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) and Short-Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study.

BackgroundImmunocompromised patients have lower seroconversion rate in response to COVID-19 vaccination. The aim of this study is to evaluate the humoral immune response with short-term clinical outcomes in solid organ transplant recipients vaccinated with SARS-CoV-2 vaccine (BBIBP-CorV; Sinopharm).MethodsThis prospective cohort was conducted from March to December 2021 in Abu Ali Sina hospital, Iran. All transplant recipients, older than 18 years were recruited. The patients received two doses of Sinopharm vaccine 4 weeks apart. Immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 after the first and second dose of vaccine. The patients were followed up for 6 months after vaccination.ResultsOut of 921 transplant patients, 115 (12.5%) and 239 (26%) had acceptable anti S-RBD immunoglobulin G (IgG) levels after the first and second dose, respectively. Eighty patients (8.68%) got infected with COVID-19 which led to 45 (4.9%) of patients being hospitalized. None of the patients died during follow-up period. Twenty-four (10.9%) liver transplant recipients developed liver enzyme elevation, and increased serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two patients experienced biopsy-proven rejection without any graft loss.ConclusionOur study revealed that humoral response rate of solid organ transplant recipients to Sinopharm vaccine was low.

Effects of Panax Ginseng on Health-Related Quality of Life in Patients with Non-Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Ginseng for HRQOL in Breast Cancer.

Being diagnosed with cancer and chemotherapy impose distressing symptoms on patients' Health-Related Quality of Life (HRQOL). This study evaluated ginseng efficacy on improving multiple aspects of HRQOL in breast cancer patients. Forty women with non-metastatic early breast cancer were enrolled in the study. Participants received ginseng (1 g/day) or placebo with standard chemotherapy. HRQOL was evaluated via in-person interviews at baseline, two weeks after the second and last chemotherapy cycles. The FACT-B, a 37-item questionnaire composed of five subscales including physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and Breast Cancer Subscale (BCS) was employed to assess HRQOL. A considerable decreasing trend in the mean scores of all subscales, as well as the total score, was observed in the placebo group; nevertheless, the ginseng group experienced a slight decrease in the PWB subscale and a constant or even increasing trend in other subscales and total score. The differences in the mean change of scores during the study period were statistically significant in all domains between the two groups (all p-values < 0.001). Regular ginseng supplementation may provide beneficial effects on enhancing different aspects of HRQOL including PWB, SWB, EWB, FWB, and BCS in breast cancer patients.This study was registered in the Iranian Registry of Clinical Trials (IRCT, IRCT20141227020441N7) in Jan 2020.

Frequency of Visual Fields Needed to Detect Glaucoma Progression: A Computer Simulation Using Linear Mixed Effects Model.

PRCIS: Irregular visual field test frequency at relatively short intervals initially and longer intervals later on in the disease provided acceptable results in detecting glaucoma progression. PURPOSE: It is challenging to maintain a balance between the frequency of visual field testing and the long-term costs that may result from insufficient treatment of glaucoma patients. This study aims to simulate real-world circumstances of visual field data to determine the optimum follow-up scheme for the timely detection of glaucoma progression using a linear mixed effects model (LMM). MATERIALS AND METHODS: An LMM with random intercept and slope was used to simulate the series of mean deviation sensitivities over time. A cohort study including 277 glaucoma eyes that were followed for 9.0±1.2 years was used to derive residuals. Data were generated from patients with early-stage glaucoma having various regular and irregular follow-up scenarios and different rates of visual field loss. For each condition, 10,000 series of eyes were simulated, and one confirmatory test was conducted to identify progression. RESULTS: By doing one confirmatory test, the percentage of incorrect progression detection decreased considerably. The time to detect progression was shorter for eyes with an evenly spaced 4-monthly schedule, particularly in the first 2 years. From then onward, results from twice-a-year testing were similar to results from examinations scheduled 3 times per year. CONCLUSIONS: Irregular visual field test frequency at relatively short intervals initially and longer intervals later on in the disease provided acceptable results in detecting glaucoma progression. This approach could be considered for improving glaucoma monitoring. Moreover, simulating data using LMM may provide a better estimate of the disease progression time.

Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA.

OBJECTIVE: This study aimed to evaluate the effectiveness of metformin versus placebo in overweight patients with knee osteoarthritis (OA). In addition, to assess the effects of inflammatory mediators and apoptotic proteins in the pathogenesis of OA, the genetic polymorphisms of two genes, one related to apoptosis (rs2279115 of Bcl-2) and the other related to inflammation (rs2277680 of CXCL-16), were investigated. METHODS: In this double-blind placebo-controlled clinical trial, patients were randomly divided to two groups, one group receiving metformin (n = 44) and the other one receiving an identical inert placebo (n = 44) for 4 consecutive months (starting dose 0.5 g/day for the first week, increase to 1 g/day for the second week, and further increase to 1.5 g/day for the remaining period). Another group of healthy individuals (n = 92) with no history and diagnosis of OA were included in this study in order to evaluate the role of genetics in OA. The outcome of treatment regimen was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. The frequency of variants of rs2277680 (A181V) and rs2279115 (938C>A) were determined in extracted DNAs using PCR-RFLP method. RESULTS: Our results indicated an increase in scores of pain (P ≤ 0.0001), activity of daily living (ADL) (P ≤ 0.0001), sport and recreation (Sport/Rec) (P ≤ 0.0001), and quality of life (QOL) (P = 0.003) and total scores of the KOOS questionnaire in the metformin group compared to the placebo group. Susceptibility to OA was associated with age, gender, family history, CC genotype of 938C>A (Pa = 0.001; OR = 5.2; 95% CI = 2.0-13.7), and GG+GA genotypes of A181V (Pa = 0.04; OR = 2.1; 95% CI = 1.1-10.5). The C allele of 938C>A (Pa = 0.04; OR = 2.2; 95% CI = 1.1-9.8) and G allele of A181V (Pa = 0.02; OR = 2.2; 95% CI = 1.1-4.8) were also associated with OA. CONCLUSION: Our findings support the possible beneficial effects of metformin on improving pain, ADL, Sport/Rec, and QOL in OA patients. Our findings support the association between the CC genotype of Bcl-2 and GG+GA genotypes of CXCL-16 and OA.

Quality of life associated with immunosuppressant treatment adherence in liver transplant recipients: A cross-sectional study.

Purpose: Transplanted organ survival after solid organ transplantation highly correlates with the adherence levels of the patients to their immunosuppressive drugs. On the other hand, one of the main goals of liver transplantation is to increase the overall quality of life (QOL) for the patient. This study is aimed to analyze the relationship between adherence and QOL in adult liver transplant recipients of the biggest liver transplant center in Asia. Methods: All of the included patients were older than 18 years and at least 6 months had passed from their liver transplantation. The adherence level was measured with BAASIS method and the QOL was assessed by SF-36 questionnaire in real-time interviews. The relationship between adherence and different aspects of QOL in addition to qualitative and quantitative influential factors on these two outcomes was calculated with statistical analysis. Results: Among the 122 included patients, 41% of the were categorized in the non-adherent group. The most important reasons for non-adherence in these patients included forgetfulness (62%), lack of medication (12%), financial problems for drug supply (9%), and side effects (2%). According to the results of the multivariate linear regression model, rejection was the only influential factor in the occurrence of non-adherence among patients (OR = 8.226 CI (1.404-48.196)). The overall mean QOL score of patients was reported 51.09 ± 21.86. The lowest is given to social functioning, while mental health has achieved the highest score. The mean QOL scores in different dimensions in patients with adherence were higher than non-adherents, which was only significant in mental health (p-value = 0.01). Additionally, in total scores related to Physical Composite Score (PSC) and Mental Composite Score (MCS), the mean MSC scores in adherent patients were significantly higher than non-adherent patients (p-value: 0.02). Although adherent patients have an overall greater QOL, the only meaningful effect on QOL total score was from income level. Conclusion: The overall QoL score has been in all parameters higher in the adherent group compared with non-adherent patients. The difference in QoL was most meaningfully significant in mental composite score among other parameters of QoL.

Protective effects of Panax ginseng against doxorubicin-induced cardiac toxicity in patients with non-metastatic breast cancer: A randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Anthracycline-based chemotherapy increases the risk of cancer therapeutics-related cardiac dysfunction. Recently, evidences from in vitro experiments and animal studies have shown that ginsenosides may exert cardiovascular protection against cancer therapeutics-related cardiac dysfunction. Here, we aimed to evaluate this effect in a clinical situation. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, women with non-metastatic breast cancer whose left ventricular ejection fraction was ≥ 50% were randomly assigned in 1:1 ratio to receive ginseng (1 g/day) or placebo besides standard chemotherapy. Echocardiographic measurements were performed at baseline, after the fourth, and eighth chemotherapy cycles. High-sensitive cardiac troponin I was assessed at baseline and after the 4th cycle. The primary endpoint of the study was change in left ventricular ejection fraction. Cancer therapeutics-related cardiac dysfunction was defined as a drop in left ventricular ejection fraction of ≥ 10% from baseline. RESULTS: Results from 30 patients were included in the final analysis (15 patients in each group). In the intervention and control groups, left ventricular ejection fraction was dropped from 62.0 ± 0.9% to 60.7 ± 1.0% (difference = -1.3 ± 1.1%) and from 63.27 ± 1.1% to 58.0 ± 1.3% (difference = -5.27 ± 0.8%), respectively (difference = 3.97%, p = 0.006) at the end of the fourth cycle of chemotherapy. After the eighth cycle of chemotherapy, the mean left ventricular ejection fraction was increased by 0.8 ± 1.3% from baseline in the intervention group, whereas the placebo group experienced a reduction of -7.3 ± 1.4% (difference = 8.1%, p-value < 0.001). None of the patients in the ginseng group in comparison to 1(6.7%, p-value = 0.5) and 5 (33.3%, p-value = 0.02) patients in the placebo group developed cancer therapeutics-related cardiac dysfunction after the fourth and eighth cycles, respectively. High-sensitive cardiac troponin I levels were not significantly different between groups. CONCLUSIONS: Prophylactic ginseng supplementation may protect against doxorubicin-induced early cancer therapeutics-related cardiac dysfunction and early decline in left ventricular ejection fraction in breast cancer patients.

Pharmacokinetic assessment of vancomycin in critically ill patients and nephrotoxicity prediction using individualized pharmacokinetic parameters.

Introduction: Therapeutic drug monitoring (TDM) and pharmacokinetic assessments of vancomycin would be essential to avoid vancomycin-associated nephrotoxicity and obtain optimal therapeutic and clinical responses. Different pharmacokinetic parameters, including trough concentration and area under the curve (AUC), have been proposed to assess the safety and efficacy of vancomycin administration. Methods: Critically ill patients receiving vancomycin at Nemazee Hospital were included in this prospective study. Four blood samples at various time intervals were taken from each participated patient. Vancomycin was extracted from plasma samples and analyzed using a validated HPLC method. Results: Fifty-three critically ill patients with a total of 212 blood samples from June 2019 to June 2021 were included in this study. There was a significant correlation between baseline GFR, baseline serum creatinine, trough and peak concentrations, AUCτ, AUC24h, Cl, and Vd values with vancomycin-induced AKI. Based on trough concentration values, 66% of patients were under-dosed (trough concentration <15 µg/ml) and 18.9% were over-dosed (trough concentration ≥20 µg/ml). Also, based on AUC24h values, about 52.2% were under-dosed (AUC24h < 400 µg h/ml), and 21.7% were over-dosed (AUC24h > 600 µg h/ml) that emphasizes on the superiority of AUC-based monitoring approach for TDM purposes to avoid nephrotoxicity occurrence. Conclusion: The AUC-based monitoring approach would be superior in terms of nephrotoxicity prediction. Also, to avoid vancomycin-induced AKI, trough concentration and AUCτ values should be maintained below the cut-off points.

Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

BACKGROUND: The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. METHOD: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. RESULTS: A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. CONCLUSION: The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

A longitudinal item response model for Aberrant Behavior Checklist (ABC) data from children with autism.

This manuscript aims to present the first item response theory (IRT) model within a pharmacometric framework to characterize the longitudinal changes of Aberrant Behavior Checklist (ABC) data in children with autism. Data were obtained from 120 patients, which included 20,880 observations of the 58 items for up to three months. Observed scores for each ABC item were modeled as a function of the subject's disability. Longitudinal IRT models with five latent disability variables based on ABC subscales were used to describe the irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech over time. The IRT pharmacometric models could accurately describe the longitudinal changes of the patient's disability while estimating different time-course of disability for the subscales. For all subscales, model-estimated disability was reduced following initiation of therapy, most markedly for hyperactivity. The developed framework provides a description of ABC longitudinal data that can be a suitable alternative to traditional ABC data collected in autism clinical trials. IRT is a powerful tool with the ability to capture the heterogeneous nature of ABC, which results in more accurate analysis in comparison to traditional approaches.

Adjusted adaptive Lasso for covariate model-building in nonlinear mixed-effect pharmacokinetic models.

One important aim in population pharmacokinetics (PK) and pharmacodynamics is identification and quantification of the relationships between the parameters and covariates. Lasso has been suggested as a technique for simultaneous estimation and covariate selection. In linear regression, it has been shown that Lasso possesses no oracle properties, which means it asymptotically performs as though the true underlying model was given in advance. Adaptive Lasso (ALasso) with appropriate initial weights is claimed to possess oracle properties; however, it can lead to poor predictive performance when there is multicollinearity between covariates. This simulation study implemented a new version of ALasso, called adjusted ALasso (AALasso), to take into account the ratio of the standard error of the maximum likelihood (ML) estimator to the ML coefficient as the initial weight in ALasso to deal with multicollinearity in non-linear mixed-effect models. The performance of AALasso was compared with that of ALasso and Lasso. PK data was simulated in four set-ups from a one-compartment bolus input model. Covariates were created by sampling from a multivariate standard normal distribution with no, low (0.2), moderate (0.5) or high (0.7) correlation. The true covariates influenced only clearance at different magnitudes. AALasso, ALasso and Lasso were compared in terms of mean absolute prediction error and error of the estimated covariate coefficient. The results show that AALasso performed better in small data sets, even in those in which a high correlation existed between covariates. This makes AALasso a promising method for covariate selection in nonlinear mixed-effect models.

Growth Velocity of Infants From Birth to 5 Years Born in Maku, Iran.

BACKGROUND: Growth velocity standards are essential for proper evaluation of child growth. The goal of this study was to construct weight, height and head circumference growth velocity charts for infants. METHODS: This study includes 256 infants (124 boys and 132 girls) born in Maku, Northwest of Iran, and monitored from birth until they were 5 years. The weights and heights of the subjects were recorded at birth, one, two, four, six months and 1, 1.5, 2, 3, 4 and 5 years of age, while the head circumferences were measured until they were 1.5 years old. In this study, the LMS method using LMS chart maker software, was utilized to obtain growth velocity centiles. RESULTS: Growth velocity charts for weight, height and head circumference (5th, 50th, 95th percentiles) were obtained. The velocity growth charts decreased rapidly from birth to 2 years and then remained relatively constant up to 5 years for both sexes. The growth velocity of boys was higher than girls through the first year of age but became equal at 12 months of age and no significant difference was seen up to 5 years. CONCLUSION: Growth velocity studies are really sparse in Iran. In this study, longitudinal data were used to obtain growth velocity centiles. Furthermore, the weight and height velocities of infants from Shiraz, southern Iran, and U.K were compared.

Child Weight Growth Chart and Its Associated Factors in Birth Cohort of Maku Using a Growth Curve Model and LMS Method.

BACKGROUND: Infant growth is defined as a positive change in body size over a period of time, and is a sensitive predictor of social health. The most effective way to determine child growth is by measuring birth weight and constructing a weight growth trajectory. Many studies were conducted on the effects of different factors on birth weight, but investigations of these effects on growth trajectory are really sparse. This study analyzes longitudinal data to determine factors affecting growth trajectory and used LMS chart for comparing children. MATERIALS AND METHODS: In a cohort study, 256 neonates born in 2004 in Maku, Iran, were recruited and were followed until 2009.The weight of the neonates were measured at 12 occasions from birth, until the age of 5 years. A growth curve model was used to determine the affecting factors. The parametric LMS method was used to construct the reference centiles curve of the weight (5th, 50th, 95th percentiles). FINDINGS: The findings show that while controlling the other factors, birth region, breast feeding duration, mother's education and infants' gender significantly influenced the longitudinal weight rate. However, other variables did not reveal any significant association with growth. The growth charts increased rapidly from birth to 5 years of age for both sexes. It was observed that male children grew faster than females, through the first year of age up to 5 years. CONCLUSION: Although every child has a growth potential, this capacity could be influenced by various factors and can be compared with other infants through a growth chart. We used longitudinal data to obtain the risk factor of growth trajectory. LMS method was also used for description of growth. Thereafter, the weight chart of Shiraz, southern Iran's corresponding infants, was compared.

Longitudinal standards for growth velocity of infants from birth to 4 years born in West Azerbaijan Province of northwest Iran.

OBJECTIVES: Growth velocity is an important factor to monitor for appropriate child growth. This study presents the growth velocity of infants based on length, weight, and head circumference. METHODS: The subjects of this study were 308 neonates (160 boys and 148 girls) born in West Azerbaijan Province of northwestern Iran who were followed from birth for 4 years. The weights and lengths of the subjects were recorded at birth, 1, 2, 4, 6, and 9 months, and 1, 1.5, 2, 3, and 4 years of age, while the head circumferences were measured just up to 1.5 years of age. In this study, the Lambda-Mu-Sigma (LMS) method using LMS Chartmaker Pro (Institute of Child Health, London, UK) was utilized to obtain growth velocity percentiles. RESULTS: After obtaining growth velocity charts for weight, length, and head circumference (5th, 50th, and 95th percentiles), the researchers could deduce that there was a sharp decrease in the velocity growth charts from birth to 2 years of age but these charts remained relatively stable up to 4 years for both sexes. Growth velocities for the length and weight of boys in the present sample are slightly but not significantly greater than those in girls through the first months of infancy and there was no significant difference between girls and boys up to 4 years. CONCLUSIONS: This paper provided the first local growth velocity standards of length, weight, and head circumference for infants by analyzing longitudinal measurements produced for West Azerbaijan Province, which should be updated periodically. It seems that there has been a significant difference between the growth velocity of infants in northwestern Iran and southern Iran within the past few years.

Breast cancer risk factors in a defined population: weighted logistic regression approach for rare events.

PURPOSE: This study aimed to determine out risk factors for female breast cancer in a low socioeconomic population in Iran. METHODS: Between 2007 and 2009, a total of 25,592 women who were ensured by the Imam Khomeini Relief Foundation participated in this screening program. The characteristics of patients diagnosed with breast cancer (n=111) were compared with those of control cases (n=25,481). In this study, we used relogit analysis (rare event logistic regression) with a weighting method using program Zelig. RESULTS: Of 25,592 women, 3.9/1,000 had breast cancer, from which 38 were diagnosed during screening and 73 had already been diagnosed. The mean and standard deviation of age in breast cancer patients and in healthy controls were 49.18±8.86 years and 46.65±9.40 years, respectively. The findings based on the multivariate model revealed that the past history of ovarian cancer, hormone therapy, and first relatives with breast cancer were associated with increased risk for breast cancer. However, the use of oral contraceptive pills was found to be associated with reduced risk for breast cancer. CONCLUSION: Due to the rarity of the event in the population, relogit with a weighting method was used to investigate the major risk factors for breast cancer. These factors include oral contraceptive pill use, a history of ovarian cancer of the person under study, first relatives with breast cancer and hormone therapy.