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Evaluation of the Effect of Combination Therapy on Treatment of COVID-19: A Cohort Study
Background: COVID-19 is a new disease for which a definitive treatment has not yet been proposed.
Objectives: The present study aimed to investigate the effect of combination therapy on the treatment of COVID-19 due to the importance
of finding an appropriate treatment for this epidemic disease.
Methods: This two-center cohort study included 175 confirmed COVID-19 inpatients at two medical centers designated for the treatment
of COVID-19 patients in Qom and Qazvin, Iran. In this study, four different groups of drug regimens were studied which included
G1 (azithromycin, prednisolone, and naproxen), G2 (lopinavir/ritonavir, azithromycin, naproxen, and prednisolone), G3
(hydroxychloroquine, azithromycin, naproxen, and prednisolone), and G4 (levofloxacin, vancomycin, hydroxychloroquine, and
oseltamivir). It should be noted that G1, G2, G3, and G4 treatment regimens were used on 48, 39,30, and 77 patients, respectively.
Results: The study participants included 175 confirmed COVID-19 patients with mean±SD age of 58.9 ±15.1 years, out of whom 80 (46%)
patients were male and the rest were females. The results indicated that the hospital stay period was significantly shorter in the G1
compared to other groups (G1:5.9±2.4, G2:8.1±4.2, G3: 6.3±1.7, and G4: 6.4±2.9; [P-value=0.008]). It should be noted that pulse rate,
oxygen saturation, hemoglobin, and platelet count (PLT) changed significantly during the study in four treatment groups; however, a
significant change in temperature, creatinine, and white blood cell (WBC) was observed only in G3, G4, and G1 groups, respectively. The
number of ICU admissions and deaths were not statistically significant among the patients who received the four treatment regimens
(P=0.785). Based on the results, the history of ischemic heart disease, baseline oxygen saturation, WBC, neutrophil, lymphocyte count, and
C-reactive protein (CRP) are the risk factors for the prolonged hospital stay in COVID-19 patients.
Conclusion: The obtained results in this study indicated that the combination of azithromycin, prednisolone, and naproxen is the most
effective regimen for the treatment of COVID-19, compared to three other combination treatment regimens.
Keywords: Anti-inflammatory drugs, Antiviral drugs, Combination therapy, Corticosteroid, COVID-19, Immunomodulators drug
The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran
Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most
common cancers in the world. Hence, the determination of risk factors of UGI helps to
reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study,
we examine the causal effect of opium use on the time to UGI cancer death. Based on the
Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to
the study for four years (2004–2008) and followed annually until July 2018. We used
“parametric g-formula” to study the causal effect of opium use on the time to death due to
UGI. In this study, the information of 49946 individuals due to missingness were analyzed.
So the median of follow-up time was 144 months and the prevalence of opium use was 17%
(about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to
UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula =
1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI
cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results
showed a causal effect of opium use on the intensity of upper gastrointestinal cancer deat
Opium-associated QT Interval Prolongation: A Cross-sectional Comparative Study
Background: Toxicity and side effects of long-term use of opioids are well studied, but little information exists regarding electrophysiological
disturbances of opium consumption. While natural opium has been regarded safe to a great extent among traditional communities, concerns
are emerging owing to the available evidence of QT prolongation that have been exposed during recent outcome surveillance of patients
under opioid use. Potential QT prolonging interactions would raise a higher level of such concern in opium users during COVID pandemic and
warrant attention.
Materials and methods: This study was designed to detect the prevalence of QTc prolongation among opium users and nonusers. Two groups
were compared with regard to gender, age, and median QTc interval. Normal and prolonged QTc intervals of user group were compared with
respect to age, sex, dose of opium consumption, and duration of opium consumption.
Results: 123 opium users and 39 controls were investigated. Median QTc interval in opium user and non-user group was 460 vs 386 milliseconds,
respectively (p value < 0.001). In all, 59.3%, (95% CI: 50.51–67.62%) of cases and none of non-user had prolonged QTc interval (p value < 0.001).
There was no significance between normal and prolonged QTc intervals with respect to dose and duration of opium use.
Conclusion: This study indicated that opium consumption is associated with QTc prolongation. This prolongation does not relate to dose and
duration of opium use. Further study is propounded to assess the clinical significance of these results and to determine risk rating of opium
compared to other opioids in this regard.
Keywords: Opioids, Opium, QT interval, QT prolongation.
Indian Journal of Critical Care Medicine (2020): 10.5005/jp-journals-10071-2359
Lived Experiences of the Patients Hospitalized with COVID-19: A Phenomenological Study in a Province of Northwest Iran
Abstract: Abstract: COVID-19 is a serious infectious disease whose rapid and widespread
spread urged the World Health Organization to declare it a global public health emergency.
Understanding the experience of people infected and quarantined with COVID-19 is very
important in maximizing disease control and minimizing the negative effects on patients,
their families, and social networks. This study explored the experiences of patients with
COVID-19 during care and quarantine in northwest Iran. A purposive sample of 11 patients
with COVID-19 was recruited. Data were collected from the beginning of March to the
beginning of June 2020, using semi‐structured interviews and these were analyzed
according to van Manen's phenomenological method. Interviews were audiotaped,
transcribed verbatim and analyzed using thematic analysis.
Ultimately, four themes, Characteristics of the experience, Response to traumatic
experience, Deprivation, and Confusion, and containing 19 sub-themes, emerged. After
understanding the findings of this research, nurses working in the wards of patients with
COVID-19 can better consider the importance of assessing and analyzing the challenges
and experiences of patients during periods of illness and quarantine. Findings also
enhance the identification and organization of training needs during such a pandemic
and the design of nursing programs to respond to them
Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients
Mutations in adaptor protein complex-4 (AP-4) genes have first been identified in
2009, causing a phenotype termed as AP-4 deficiency syndrome. Since then several
patients with overlapping phenotypes, comprised of intellectual disability (ID) and
spastic tetraplegia have been reported. To delineate the genotype-phenotype correlation of the AP-4 deficiency syndrome, we add the data from 30 affected individuals
from 12 out of 640 Iranian families with ID in whom we detected disease-causing
variants in AP-4 complex subunits, using next-generation sequencing. Furthermore,
by comparing genotype-phenotype findings of those affected individuals with previously reported patients, we further refine the genotype-phenotype correlation in this
syndrome. The most frequent reported clinical findings in the 101 cases consist of ID
and/or global developmental delay (97%), speech disorders (92.1%), inability to walk
(90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been
reported in 72.3% of the investigated patients. The major brain imaging findings are
abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly
(44.5%). Our result might suggest the AP-4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders
Functional differences of Toll-like receptor 4 in osteogenesis, adipogenesis and chondrogenesis in human bone marrow- derived mesenchymal stem cells
Multipotent human bone marrow-derived mesenchymal stem cells (hMSCs) are promising candidates for bone and cartilage regeneration. Toll-like receptor 4 (TLR4) is expressed by hMSCs and is a receptor for both exogenous and endogenous danger signals. TLRs have been shown to possess functional differences based on the species (human or mouse) they are isolated from therefore, the effects of knockdown of TLR4 were evaluated in humans during the differentiation of MSCs into bone, fat and chondrocyte cells in vitro. We investigated the expression profile of TLR4 during the differentiation of hMSCs into three different lineages on days 7, 14 and 21 and assessed the differentiation potential of the cells in the presence of lipopolysaccharide (LPS, as an exogenous agonist) and fibronectin fragment III-1c (FnIII-1c, as an endogenous agonist). TLR4 expression increased following the induction of hMSC differentiation into all three lineages. Alkaline phosphatase activity revealed that FnIII-1c accelerated calcium deposition on day 7, whereas LPS increased calcium deposition on day 14. Chondrogenesis increased in the presence of LPS; however, FnIII-1c acted as a reducer in the late stage. TLR4 silencing led to decreased osteogenesis and increased adipogenesis. Furthermore, Wnt5a expression was inversely related to chondrogenesis during the late stage of differentiation. We suggest that understanding the functionality of TLR4 (in the presence of pathogen or stress signal) during the differentiation of hMSCs into three lineages would be useful for MSC-based treatments
Protective efficacy by a novel multi-epitope vaccine, including MIC3, ROP8, and SAG1, against acute Toxoplasma gondii infection in BALB/c mice
Toxoplasma gondii is an intracellular apicomplexan parasite, which can cause a serious infectious disease in pregnant women and immunocompromised individuals. Therefore, the development of a polyvalent vaccine consisting of all stages of the parasite life cycle using the epitopes from tachyzoites, bradyzoites, and sporozoites is likely to be required for complete protective immunity. In this study, we designed protein vaccine candidate based on the prediction of specific epitopes (i.e., B cell and T cell) from three Toxoplasma gondii antigens. The MRS protein (MIC3: 30–180, ROP8: 85–185, and SAG1: 85–235) was expressed in Escherichia coli, and purification was performed using a HisTrap HP column and then we evaluated immunogenicity and protective property in BALB/c mice. Seventy-two mice were randomly divided into six groups, including three vaccinations (i.e., MRS, MRS-Freund, and MRS-Calcium Phosphate Nanoparticles (MRS-CaPNs)) and three control (i.e., Phosphate-buffered saline, Freund, and CaPNs) groups. All groups were immunized three times via subcutaneous injection within three-week intervals. In the vaccination groups, the BALB/c mice were injected with 20 μg of MRS protein for the first time and 10 μg of MRS for the next two times. Antibodies, cytokines, and splenocytes proliferation in the immunized mice were assayed using the enzyme-linked immunosorbent assay. Protective efficacy was analyzed by challenging the immunized mice with T. gondii of RH strain. Antibody, cytokine, and lymphocyte proliferation assays showed that the mice immunized with MRS induced stronger humoral and T helper type 1 cell-mediated immune responses, compared to the control mice. However, co-immunization with adjuvants (i.e., Freund and CaNPs) resulted in impaired immune responses. Effective protection against the parasite achieved an increase in survival time in the immunized mice, especially in the MRS-CaNPs group. The obtained results of the present study demonstrated that multi-epitope protein vaccination, MRS, is a potential strategy against toxoplasmosis infection. In addition, the vaccine co-delivered with CaPNs could provide an important key for vaccine candidate to control T. gondii infection. © 2021 Elsevier Ltd
Author keywords
Calcium phosphate; Freund; Multi-epitope; Protein vaccine; Toxoplasma gondi
Daytime napping and nighttime sleep during pregnancy and preterm birth in iran
Objectives: This study investigated the relationship between sleep quality during pregnancy and preterm birth.
Methods: This longitudinal study was conducted between August 2018 and May 2019. The participants were 150 pregnant women
who had been referred to 7 healthcare centers in the city of Qazvin, Iran and met the inclusion criteria. The Petersburg Sleep Quality
Index, the Epworth Sleepiness Scale, and 2 questions about daytime sleep status and a demographic questionnaire were administered at 14-18 weeks and 28-32 weeks of gestation. Data were analyzed using the Mann-Whitney test, the Fisher exact test, and univariate and multivariable logistic regression.
Results: In the present study, poor sleep quality affected 84.7% of the participants at 14-18 weeks and 93.3% at 28-32 weeks of gestation. The final model for preterm birth prediction incorporated age and the Petersburg Sleep Quality Index score in the second and
third trimesters. Preterm birth increased by 14% with each unit increase in age. With each unit increase in the Petersburg Sleep Quality Index score in the second and third trimesters, preterm birth increased by 42% and 28%, respectively, but the p-values of these factors were not significant.
Conclusions: Although a significant percentage of pregnant women had poor sleep quality, no significant relationship was found between sleep quality during pregnancy and preterm birth
Opium-associated QT Interval Prolongation: A Cross sectional Comparative Study
Background: Toxicity and side effects of long-term use of opioids are well studied, but little information exists regarding electrophysiological
disturbances of opium consumption. While natural opium has been regarded safe to a great extent among traditional communities, concerns
are emerging owing to the available evidence of QT prolongation that have been exposed during recent outcome surveillance of patients
under opioid use. Potential QT prolonging interactions would raise a higher level of such concern in opium users during COVID pandemic and
warrant attention.
Materials and methods: This study was designed to detect the prevalence of QTc prolongation among opium users and nonusers. Two groups
were compared with regard to gender, age, and median QTc interval. Normal and prolonged QTc intervals of user group were compared with
respect to age, sex, dose of opium consumption, and duration of opium consumption.
Results: 123 opium users and 39 controls were investigated. Median QTc interval in opium user and non-user group was 460 vs 386 milliseconds,
respectively (p value < 0.001). In all, 59.3%, (95% CI: 50.51–67.62%) of cases and none of non-user had prolonged QTc interval (p value < 0.001).
There was no significance between normal and prolonged QTc intervals with respect to dose and duration of opium use.
Conclusion: This study indicated that opium consumption is associated with QTc prolongation. This prolongation does not relate to dose and
duration of opium use. Further study is propounded to assess the clinical significance of these results and to determine risk rating of opium
compared to other opioids in this regard