The Cochrane risk of bias assessment tool 2 (RoB 2) versus the original RoB: A perspective on the pros and cons.

Background and Aims: Critical appraisal or risk of bias assessment is a fundamental part of systematic reviews that clarifies the degree to which included research articles are qualified and reliable. Version 2 of the Cochrane tool for assessing the risk of bias in randomized trials (RoB 2), the updated version of the first tool, was released in 2019. Here, we have compared these two versions of Cochrane risk of bias assessment tools and highlighted the pros and cons of RoB 2. Methods: Statistical analysis and methodology is not applicable to this article as no new data were created or analyzed in this study. Results: The overall approach in RoB 2 is that by answering some signaling questions after the specification of results, effects of interest, and sources of information, an overall judgment for the quality of each study is reached. Accordingly, in the original version of the Cochrane RoB tool, the judgment can be in three different conclusions, including low, unclear, and high risk of bias. The most prominent difference in bias domains is the removal of "other bias" domain being replaced by "overall bias" judgment. Also, the most common presentation types of Cochrane risk of bias assessments are the "summary" and "graph" which are generated by Review Manager, web-based applications, or packages in R software. Conclusion: The RoB 2 tool, compared to the original RoB, has improved and is the recommended version by the Cochrane Collaboration for quality assessment of randomized controlled trials. It is recommended to consider funding source, duration of follow-up, declaration of data availability, the status of baseline characteristics between groups, and sample size calculation methods in further revisions of the Cochrane risk of bias assessment tools.

Optimal sizing of residential photovoltaic and battery system connected to the power grid based on the cost of energy and peak load.

The use of renewable energy is necessary to achieve the goals of sustainable development, and sooner or later all countries are forced to plan and make policies for the use of this equipment. Considering the growing trend of smart systems and the ability of these systems to control and use renewable resources, it is necessary to investigate how to control and optimally use these resources in smart systems. Considering the geographical conditions and significant solar energy radiation in Iran, the most suitable option for using renewable energy in residential buildings is solar energy. Among the types of solar energy used around the world, photovoltaic panels are used more due to their wide range, being cheaper than other sources of electric power from solar energy and more durable than other sources. In order to reduce widespread losses and reduce the cost of transmission and distribution, increase efficiency, the possibility of the presence of private sector investors and increase the security and stability of the power grid, distributed production of electrical energy at consumption locations using small-scale units is the most cost-effective way to use home solar panels. Also, the production of energy from wind turbines can be done in the areas where anemometer data determine it to be suitable. The combination of solar energy and wind energy can effectively reduce the need for batteries, but studies show that this combination is only economically viable when it is used on a large scale and with high powers, which requires a lot of investment. Large initial capital is one of the biggest problems of distributed production systems, so the use of artificial intelligence methods for accurate capacity determination of renewable energy production systems becomes doubly important. The economic results show that the least cost of electricity and net price cost are 0.44 $ per kWh and 15.0 million $ respectively, when the converter size was gradually changed, with a renewable fraction of 46.7%.

The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects.

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.

Comprehensive Assessment of Skin Disorders in Patients with Common Variable Immunodeficiency (CVID).

BACKGROUND: Common variable immunodeficiency (CVID) is an inborn error of immunity (IEI) characterized by various clinical manifestations such as hypogammaglobulinemia, recurrent infections, and autoimmune diseases. Among different clinical manifestations, skin manifestations have been less reported in these patients. METHODS: In this study, we investigated the prevalence of dermatologic features in 387 CVID patients. Demographic information, clinical manifestations, laboratory data, and genetic findings were collected from medical records. All data were analyzed based on the presence or absence of skin disorders in CVID patients. RESULTS: We observed at least one skin manifestation in about 40% of these patients. Among these complications, skin infection (n = 64, 42.1%) was the most frequent presentation, followed by non-infectious skin lesions (n = 54, 35.6%). Among skin infections, abscesses (n = 34, 22.4%) were the most common complication. Skin infections such as cellulitis, impetigo, measles, and warts were also documented. Eczema (n = 34, 22.4%) was the most common complication in atopic lesions, and vitiligo (n = 13, 8.5%) was prevalent in autoimmune/pigmentation disorders. Among all the patients with genetic mutations, one-quarter had a deleterious mutation in the LRBA gene, relating to the autoimmune and atopic skin lesions. CONCLUSION: This rate of skin disorders in our cohort demonstrating these manifestations could be significant in CVID patients, and they are not rare. Low data of skin complications in CVID patients could be attributed to insufficient attention of physicians and also might alert dermatologists to perform immunological investigations in children with certain skin manifestations.

Health Care Policies and COVID-19 Prevalence: Is There Any Association?

The coronavirus disease 2019 (COVID-19) pandemic has affected almost all countries and territories. As of December 6, 2020, the United States of America and India have the highest prevalence. Each country has implemented different strategies to control and reduce the spread of disease. Here, the association between prevalence number and health policies is evaluated by comparing 2 groups of countries: (1) Italy, the United States of America, Germany, Spain, and India with a higher prevalence than a linear trend line; and (2) Singapore and China with a lower or equal prevalence than linear forecasts. A rapid overview revealed that many countries have similar strategies for controlling COVID-19, including the suspension of air travel, the lockdown on the cities with the most cases detected, active case findings, monitoring of close contacts, and raising public awareness. Also, they used a gradual and phased plan to reopen activities. So, the difference between countries in the burden of COVID-19 can be attributable to the strict mode and nonstrict mode of implementation of strategies. Limitations at the national levels call for systemic rather than regional strategies.

COVID-19 Vaccine Boosters: The Good, the Bad, and the Ugly.

Pursuing vaccinations against COVID-19 brings hope to limit the spread of SARS-CoV-2 and remains the most rational decision under pandemic conditions. However, it does not come without challenges, including temporary shortages in vaccine doses, significant vaccine inequity, and questions regarding the durability of vaccine-induced immunity that remain unanswered. Moreover, SARS-CoV-2 has undergone evolution with the emergence of its novel variants, characterized by enhanced transmissibility and ability to at least partially evade neutralizing antibodies. At the same time, serum antibody levels start to wane within a few months after vaccination, ultimately increasing the risk of breakthrough infections. This article discusses whether the administration of booster doses of COVID-19 vaccines is urgently needed to control the pandemic. We conclude that, at present, optimizing the immunity level of wealthy populations cannot come at the expense of low-income regions that suffer from vaccine unavailability. Although the efficiency of vaccination in protecting from infection may decrease over time, current data show that efficacy against severe disease, hospitalization, and death remains at a high level. If vaccine coverage continues at extremely low levels in various regions, including African countries, SARS-CoV-2 may sooner or later evolve into variants better adapted to evade natural and vaccine-induced immunity, ultimately bringing a global threat that, of course, includes wealthy populations. We offer key recommendations to increase vaccination rates in low-income countries. The pandemic is, by definition, a major epidemiological event and requires looking beyond one's immediate self-interest; otherwise, efforts to contain it will be futile.

COVID-19 and Its Global Economic Impact.

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.

Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks.

Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not adequately represent genetically related coronaviruses (CoVs) [...].

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Cancer cachexia: Diagnosis, assessment, and treatment.

Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.

Individual Radiosensitivity Assessment of the Families of Ataxia-Telangiectasia Patients by G2-Checkpoint Abrogation.

OBJECTIVES: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. METHODS: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. RESULTS: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95-1.00). CONCLUSION: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers.

Costs of Hospital Admission on Primary Immunodeficiency Diseases.

BACKGROUND: Primary immunodeficiency diseases (PID) are heterogeneous group of inherited disorders mainly characterized by recurrent infections leading to several times hospital admissions. The economic impact of PID is a challenging issue; therefore, this study was designed to determine the medical costs of hospitalizations in this group of patients as an indicator of the direct cost of these diseases. METHODS: One hundred and ten children with PID hospitalized in the Children's Medical Center Hospital, Tehran, Iran were included in this study during Jan 2011 and Jan 2012. All direct costs during the admission period were calculated, using the hospital information system. RESULTS: Medical cost was 7.090$ per patient per admission. Among them, about 1.580$ belong to drug consuming during hospitalization. Anti-infective drugs for systemic use were the most cost-consuming group of drugs, followed by alimentary tract and metabolism and blood and blood forming organs agents. Investigation of anti-infective group internally showed that immune sera and immunoglobulin and antiviral agents for systemic use consisting the most important medication for PID patients during hospital admission. CONCLUSION: Although the results of economic evaluations in a region cannot necessarily be applied to other regions, having an overall estimation of hospital admission costs and types of drugs used during admission could be helpful in health policy system.

Evaluating Awareness of Pediatricians and General Practitioners on Transformation of the Health System in Iran.

In orders to promote the level of healthcare in societies, governments try to have different policies to transform the health system. The aim of this study was to measure the level of awareness of practitioners in Iran, after initiating the new transformation of the health system in the country, starting from May 2014. This is a descriptive-cross-sectional study, which was inducted in October 2014. The study population consists of 208 physicians who attended the 26th International Congress of Pediatrics in Tehran, Iran. Data was collected using a self-structured questionnaire, which was estimated as both reliable and valid. Two hundred and eight questionnaires were returned. The results showed that 79.1% of the practitioners were aware of the new health system. Indeed 48.3% of the participants believed that the system was successful. 57.7% of physicians were completely aware of the time of the new system settlement in the country, while the rest had either no idea or did not know the exact date. The participants suggested a few items promote the health system in the country; among them, decreasing the direct payment between patients and physicians was suggested most frequently. According to the results obtained from the study, it is suggested that health care administrators have a detailed plan for health care workers prior to settlement of a new health policy installment, in order to succeed in settlement of a program.

Cost-effectiveness analysis of subcutaneous immunoglobulin replacement therapy in Iranian patients with primary immunodeficiencies.

Background: Economic evaluation of subcutaneous immunoglobulin therapy (SCIG) is important, and it has recently been used for treatment of patients with primary immunodeficiency (PID) diseases, and can improve allocation of resources in health care systems. The present research aimed at providing an economic assessment of SCIG and IVIG (intravenous immunoglobulin therapy) administration in Iran. Methods: Data related to clinical effectiveness were obtained from a meta-analysis. Economic analysis was performed taking into account the perspective of health care providers. Incremental cost-effectiveness ratio (ICER) was applied for economic evaluation of the 2 methods, and GDP per capita was considered as a threshold. Results: The results of meta-analysis suggested a higher effectiveness of SCIG compared to IVIG in serum immunoglobulin (Ig) levels (SMD= 0.336) and adverse effects (OR= 0.497), while the cost of IVIG was higher than SCIG ($1370 vs. $121). The ICER obtained in this paper ($2939 for adverse effects and $4348 for serum Ig level) was less than the GDP per capita in Iran ($4,916.10), and thus SCIG is a more cost-effective therapy for PID patients. Conclusion: Switching from IVIG to SCIG is cost-effective for PID patients and is approved by the health care providers' points of view in this study.

Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management.

INTRODUCTION: Common variable immunodeficiency (CVID) comprises a large heterogeneous group of patients with primary antibody deficiency. Areas covered: The affected patients are characterized by increased susceptibility to infections and low levels of serum immunoglobulin. However, enteropathy, granulomatous organ infiltrates, malignancy, inflammatory and autoimmune conditions are also prevalent. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and creates difficulties in the management of autoimmune complications affecting these patients. Expert commentary: The management of autoimmunity in patients with CVID requires special considerations because dysregulation and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.

Impact of IgE-mediated Food Allergy on Parental Quality of Life in Iranian Patients.

Food allergy is a common disorder especially in the first years of life. Strict avoidance of the responsible food is the most effective therapeutic measure so far. But this continuous vigilance could be stressful for the patient and family and decreases their quality of life (QOL). This survey was designed to evaluate the impact of IgE-mediated food allergy on parental QOL in Iranian patients and to develop a valid Persian version of "Food Allergy Quality Of Life- Parental Burden (FAQL-PB) questionnaire". 90 patients (28 females, 62 males) and their parents who were referred to the clinic of Allergy in Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran were enrolled. The questionnaire was translated with scientific method and its reliability was approved in a pilot study (ICC=0.75, cronbach-α=0.90). Among all patients the most common allergens were wheat (60%) and cow's milk (42%). The patient's age (p=0.02), parent's gender (p=0.004), mother's age (p=0.02), duration of the disease (p=0.048), and allergen multiplicity (p=0.004) were found to have the most significant correlation with family and social activity (FSA) domain. The most meaningful associations were achieved between parent's gender (p<0.001) and emotional issues (EM); as well as meal preparation (MP) with patient's age (p=0.02), parent's gender (p<0.0001) and also allergen multiplicity (p= 0.003); likewise nutrition and health concern (NH) domain with parent's gender (p<0.001). Anaphylaxis's history did not place any burden on each domain. It was concluded that presence of food allergic patients in families could considerably affect all domains of QOL.

Radioimmunotherapy in non-Hodgkin lymphoma: Prediction and assessment of response.

Non-Hodgkin lymphoma (NHL) is one of the most common malignancies and a major cause of morbidity and mortality. Radioimmunotherapy (RIT) is a novel modality for treating NHL which offers the combined use of monoclonal antibodies for specific targeting of malignant cells and radiation for killing these cells. Despite the promising results favoring RIT in several clinical studies in different target populations and NHL types, Food and Drug Administration (FDA) approval for RIT agents is restricted to a limited number of indications and agents, maybe because of several ambiguities that still exist in the field. One of these ambiguities are the lack of evidence-based prognostic factors that determine what patient population would benefit most from RIT, which is essential to know in order to optimize the efficacy and safety of treatment with RIT. As well as selecting the best patient population for RIT, it is important to assess the response to RIT in order to provide further treatment strategies or avoid unnecessary therapies and diagnostic procedures. In this review we have explored the details of how to predict the efficiency of RIT based on various prognostic factors that have been investigated in the evidence, and also discussed the proposed methods and timing schedules for assessing the response to RIT. We have also pointed out the ambiguities in the aforementioned topics, which call for more investigation.

Economic burden of common variable immunodeficiency: annual cost of disease.

OBJECTIVES: In the context of the unknown economic burden imposed by primary immunodeficiency diseases, in this study, we sought to calculate the costs associated with the most prevalent symptomatic disease, common variable immunodeficiency (CVID). METHODS: Direct, indirect and intangible costs were recorded for diagnosed CVID patients. Hidden Markov model was used to evaluate different disease-related factors and Monte Carlo method for estimation of uncertainty intervals. RESULTS: The total estimated cost of diagnosed CVID is US$274,200/patient annually and early diagnosis of the disease can save US$6500. Hospital admission cost (US$25,000/patient) accounts for the most important expenditure parameter before diagnosis, but medication cost (US$40,600/patients) was the main factor after diagnosis primarily due to monthly administration of immunoglobulin. CONCLUSION: The greatest cost-determining factor in our study was the cost of treatment, spent mostly on immunoglobulin replacement therapy of the patients. It was also observed that CVID patients' costs are reduced after diagnosis due to appropriate management.