Assessment of immunological factors in COVID-19 patients treated by convalescent plasma.

Following the outbreak of COVID-19, several immunotherapy methods were used to modulate the immune responses of patients. In this study, we aimed to evaluate the immune response to COVID-19 in patients receiving convalescent plasma. In this regard, this randomized controlled trial included 30 patients who were divided into two groups according to receiving convalescent plasma or normal control plasma. Samples from both groups were collected on days 0, 1, 3, 5 and 7 after plasma infusion. We measured the expression level of TLR7/8, IRF3/7, CTLA-4, PD-1 and T cell transcription factors by Real-time PCR in the mentioned groups. Thirteen cytokines were also evaluated using flow cytometry method. Results showed that compared to the normal control plasma group, the expression levels of TLR7, 8, IRF3, 7 and PD-1 and CTLA-4, on days 3, 5 and 7 after convalescent plasma infusion, were significantly decreased. On the other hand,  Gene expression results showed that the expression levels of Tbet, RORγ3 and Foxp3 on days 3, 5 and 7 after convalescent plasma infusion were significantly increased compared to the normal control plasma group. After convalescent plasma infusion, the viral load was significantly decreased compared to the normal control plasma group. Convalescent plasma infusion also reduced the plasma cytokines levels, including IL-6, IL-10, and IL-4, and enhanced the level of IL-2, IFN- γ and perforin comparing the normal control plasma group. According to the results, the convalescent plasma infusion led to a decrease in the expression of innate immunity receptors and an increase in the expression of transcription factors of adaptive immunity. Therefore, it may be concluded that convalescent plasma infusion can modulate the immune response. To achieve a reliable consequence, further studies are required.

High Post-Infection Protection after COVID-19 among Healthcare Workers: A Population-Level Observational Study.

Background: Even though a few years have passed since the coronavirus disease 2019 (COVID-19) outbreak, information regarding certain aspects of the disease, such as post-infection immunity, is still quite limited. This study aimed to evaluate post-infection protection and COVID-19 features among healthcare workers (HCWs), during three successive surges, as well as the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection, reactivation, re-positivity, and severity. Methods: This cross-sectional population-level observational study was conducted from 20 April 2020 to 18 February 2021. The study population included all HCWs in public or private hospitals in Fars Province, Southern Iran. The infection rate was computed as the number of individuals with positive polymerase chain reaction (PCR) tests divided by the total number of person-days at risk. The re-infection was evaluated after 90 days. Results: A total of 30,546 PCR tests were performed among HCWs, of which 13,749 (61.94% of total HCWs) were positive. Considering the applied 90-day threshold, there were 44 (31.2%) cases of reactivation and relapse, and 97 (68.8% of infected and 1.81% of total HCWs) cases of reinfection among 141 (2.64%) diagnosed cases who experienced a second episode of COVID-19. There was no significant difference in symptoms (P=0.65) or the necessity for ICU admission (P=0.25). The estimated protection against repeated infection after a previous SARS-CoV-2 infection was 94.8% (95% CI=93.6-95.7). Conclusion: SARS-CoV-2 re-positivity, relapse, and reinfection were rare in the HCW population. After the first episode of infection, an estimated 94.8% protection against recurring infections was achieved. A preprint version of this manuscript is available at DOI:10.21203/rs.3.rs-772662/v1 (https://www.researchsquare.com/article/rs-772662/v1).

Factors contributing to the burnout of the faculties of a medical university in Iran: A cross-sectional study.

BACKGROUND AND AIMS: Faculty members confront a variety of obstacles over time, the most recent of which is the coronavirus disease 2019 pandemic, which may increase their vulnerability to burnout (BO). This study aims to examine BO in medical school faculties, as well as the factors that lead to BO and well-being in them. METHODS: This cross-sectional study was conducted in 2021 using online questionnaires completed by 222 faculty members of a medical university in Iran. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and the Well-being index (WBI) were used. Additionally, we gathered individual-level profiles (demographic, well-being) and occupational information (job profile, attitude toward work). RESULTS: A total of 60 (27%) faculties reported having high BO, and 112 (50.5%) reported having low well-being. Being female (odds ratio, OR = 2.69), having time to spend with the family (OR = .26), the intent of turnover (OR = 8.65), job recommendation to the offspring (OR = .26), and experiencing violence last year (OR = 2.97) were some of the individual-level factors and job-related attitudes associated with a higher BO. In the neural network for BO, the most important variables were the intention of turnover, followed by adequate family time. CONCLUSION: One third of the responding faculty reported severe BO, and BO was found to be significantly associated with lower well-being. The increased levels of BO and a decreased experience of well-being were both associated with a higher intention of turnover. According to the study, it is important to pay attention to both clinical and nonclinical field faculty members, female faculty members, those who have a high workload, and members who have experienced violence in the workplace. By acknowledging the unique challenges and experiences faced by these individuals, tailored measures can be developed to address their specific concerns and foster a supportive and inclusive environment.

Absence of Asymptomatic Malaria Reservoirs in an Area with a Previous History of Local Malaria Transmission: A Successful Experience in Line with the Malaria Elimination Program in Iran.

Background: Asymptomatic malaria is a major challenge to be addressed in the implementation of the malaria elimination program. The main goal of the malaria surveillance system in the elimination phase is to identify reliably all the positive cases of malaria reliably (symptomatic and asymptomatic) in the shortest possible time. This study focused on the monitoring of asymptomatic malaria reservoirs in areas where local transmission had been previously established. Methods: It was a case-study approach that was conducted in the Anarestan area. A total of 246 residents and immigrants living in the area at the age range of 4-60 years old were randomly selected to be tested for malaria by microscope, RDT, and nested-PCR techniques. The inclusion criterion for participants to be entered into the study was the absence of specific symptoms of malaria. Moreover, participants who have been taking antimalarials for the last month were excluded from the study. Results: The results indicated no positive cases of asymptomatic malaria among the participants tested by all methods. Conclusion: The results of this study have shown that, without concerns for asymptomatic parasitic patients, a malaria elimination program has been successfully implemented within the studies area. In addition, the findings emphasized the existence of a strong malaria surveillance system in this area.

Efficacy and safety of an inactivated virus-particle vaccine for SARS-CoV-2, BIV1-CovIran: randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial.

OBJECTIVE: To report the efficacy, safety, and exploratory immunogenicity findings of two 5 µg doses of the BIV1-CovIran vaccine. DESIGN: Randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial. SETTING: In six cities of Iran, including Bushehr, Isfahan, Karaj, Mashhad, Shiraz, and Tehran. The first vaccine or placebo injection of the first participant was on 16 May 2021 in Tehran. The last vaccine or placebo injection of the last participant occurred on 15 July 2021 in Isfahan. PARTICIPANTS: 20 000 participants aged 18-75 years were randomly assigned to the intervention or placebo groups with a ratio of 2:1. INTERVENTION: 5 µg vaccine or placebo with the interval of 28 days. MAIN OUTCOME MEASURES: Vaccine efficacy for a 90 day follow-up period, safety and explanatory immunogenicity assessment, and variant detection during the trial. RESULTS: 20 000 participants were recruited and randomly assigned to receive BIV1-CovIran (n=13 335 (66.7%)) or placebo (n=6665 (33.3%)). Participants' mean age was 38.3 (standard deviation 11.2) years, and 6913 (34.6%) were female. Among vaccinated participants that had covid-19 reported during the follow-up (median 83 days), 758 (5.9%) had symptoms, 144 (1.1%) had severe infection, and seven (0.1%) were critical. Among participants who received placebo during the follow-up, 688 (10.7%) had symptoms, 221 (3.4%) had severe infection, and 19 (0.3%) were critical. Overall efficacy was 50.2% (95% confidence interval 44.7% to 55.0%) against symptomatic covid-19, 70.5% (63.7% to 76.1%) against severe disease, and 83.1% (61.2% to 93.5%) against critical cases. Two deaths were reported in the efficacy population in the placebo group, no deaths were from the intervention group. During follow-up, 41 922 adverse events were reported: 28 782 (68.7%) were adverse reactions, of which 19 363 (67.3%) were in the intervention group. Most adverse reactions were mild or moderate in severity (grade 1 or 2) and self-limiting. No serious adverse events were related to the injections. For variant investigation, of 119 participants positive for the SARS-CoV-2 variant, 106 (89.1%) were positive for the delta variant. CONCLUSIONS: A two dose regimen of the BIV1-CovIran vaccine conferred efficacy of 50.2% against symptomatic covid-19, 70.5% against severe disease, and 83.1% against critical disease. Vaccination was well tolerated, with no safety concerns raised. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20201202049567N3. FUNDING: Shifa-Pharmed Industrial Group.

Implementation of an In-House Platform for Rapid Screening of SARS-CoV-2 Genome Variations.

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.

Advanced Theranostic Strategies for Viral Hepatitis Using Carbon Nanostructures.

There are several treatment protocols for acute viral hepatitis, and it is critical to recognize acute hepatitis in its earliest stages. Public health measures to control these infections also rely on rapid and accurate diagnosis. The diagnosis of viral hepatitis remains expensive, and there is no adequate public health infrastructure, while the virus is not well-controlled. New methods for screening and detecting viral hepatitis through nanotechnology are being developed. Nanotechnology significantly reduces the cost of screening. In this review, the potential of three-dimensional-nanostructured carbon substances as promising materials due to fewer side effects, and the contribution of these particles to effective tissue transfer in the treatment and diagnosis of hepatitis due to the importance of rapid diagnosis for successful treatment, were extensively investigated. In recent years, three-dimensional carbon nanomaterials such as graphene oxide and nanotubes with special chemical, electrical, and optical properties have been used for the diagnosis and treatment of hepatitis due to their high potential. We expect that the future position of nanoparticles in the rapid diagnosis and treatment of viral hepatitis can be better determined.

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.

Comparison of mucormycosis infection between patients with and without a history of COVID-19 infection: a retrospective cohort study.

BACKGROUND: Mucormycosis infection is a complication seen in some coronavirus disease 2019 (COVID-19) patients. This study compares the characteristics of mucormycosis infection between COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort comprised 87 patients with mucormycosis divided into two groups. The first included 44 patients who had COVID-19 recently before hospitalization due to mucormycosis at Namazi Hospital, Shiraz, Iran, between February 2019 and August 2021. The second group included all 43 patients hospitalized at the same hospital due to mucormycosis between 2010 and 2019 (pre-pandemic). RESULTS: Mucormycosis patients with a history of recent COVID-19 infection had a higher rate of diabetes mellitus, fewer malignancies and higher blood glucose, erythrocyte sedimentation rate and C-reactive protein levels (p<0.05). Glucocorticoid use was common (77%) in the COVID-19 group. CONCLUSIONS: In the pre-COVID-19 era, mucormycosis mainly affected immunodeficient patients like those receiving chemotherapy due to malignancy but now seems to affect COVID-19 patients with uncontrolled blood glucose and glucocorticoids use. Special care must be taken in prescribing glucocorticoids and controlling the blood glucose levels of COVID-19 patients.

Socioeconomic determinants of nutritional behaviors of households in Fars Province, Iran, 2018.

Introduction: Households' dietary habits are affected by their environment and socioeconomic status (SES). This study aims to investigate eating behaviors and determine the factors affecting nutritional status in households in Fars Province in 2018. Method: In this cross-sectional study, urban and rural households were selected using the multistage sampling method. A questionnaire was employed to interview the mother or householder to record the demographic, SES, and dietary habits of the family for major food items commonly used. A logistic regression model was used to analyze the data. The p-value less than 0.05 was considered significant. Results: In total, 6,429 households participated in the study. The majority of households use traditional flatbread, low-fat milk, and liquid/cooking oil. Frying was the most prevalent method of cooking. Parents' level of education and SES were associated with type of consumed bread, milk and dairy, methods of food preparation, adding salt at the table, eating out, and fast-food usage. Parents' higher level of education was significantly associated with salt storage in optimal conditions and not using salt before tasting the meal. Conclusion: Most of the households had healthy practices, especially in consumption of certain oils and methods of preparing their food as well as keeping salt in an optimal condition and using iodized salt. The most important unhealthy nutritional behavior was high consumption of fast food and outdoor food, especially in urban regions. Unhealthy dietary habits were more prevalent in households with low household and regional SES. Both households and regions with higher SES had better dietary habits.

Evaluation of the Costs and Outcomes of COVID-19 Therapeutic Regimens in Hospitalized Patients in Shiraz.

COVID-19 patients in critical conditions are hospitalized and treated with various protocols including antiviral drugs, which have been updated repeatedly. This study was aimed to analyze the demographics, costs, and outcomes of drug regimens in COVID-19 patients hospitalized in "Ali Asghar" hospital, affiliated with Shiraz University of Medical Sciences, from March 2019 to December 2020 as a retrospective study, approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1399.1003) on Dec. 28, 2020. Using hospital information system (HIS) data, 2174 patients receiving favipiravir, remdesivir, interferon-ß, and Kaletra® were analyzed. Descriptive, univariate, and regression analyses were used. The costs and consequences of different drug regimens were significantly different (P value < 0.05); the highest and lowest costs belonged to remdesivir and Kaletra®, respectively. The highest and lowest mean length of stay and mortality were related to remdesivir and favipiravir, respectively. Mortality did not differ significantly with various regimens. Length of stay was significantly shorter with favipiravir and Kaletra® than interferon-ß. Remdesivir had significantly the highest cost. Age presented a significantly positive relationship with mortality and length of stay. Besides, ICU admission significantly increased mortality, length of stay, and costs. Underlying diseases and low blood oxygen saturation contributed to mortality. COVID-19 correlation with age and underlying diseases is accordant with the published data. Given the highest costs and broad usage of remdesivir, besides controversies regarding its outcomes and side effects, a stricter evaluation of remdesivir benefits seems essential. Totally, COVID-19 therapeutic protocols should be selected carefully to optimize costs and outcomes.

Mortality-Related Risk Factors for Coronavirus Disease (COVID-19)-Associated Mucormycosis: a systematic review and meta-analysis.

Purpose of Review: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) can increase the susceptibility of individuals to contracting mucormycosis through several mechanisms. Nowadays, coronavirus disease (COVID-19)-associated mucormycosis (CAM) is a serious public health concern, particularly in developing countries. This meta-analysis aims to identify the risk factors that affect the mortality rate of patients with CAM. Recent Findings: We systematically searched PubMed, Google Scholar, Scopus, Cochrane library, and preprint databases using pertinent keywords and the reference lists of the included relevant articles from inception till October 27, 2021. In order to reduce the effects of small-scale studies, we only selected cross-sectional, case-control, and cohort studies and case series with at least four patients. We identified 26 articles that included 821 patients with CAM. The effect size (ES) of mortality rate was 28% (95% confidence interval (CI) 20%-38%; I2 =82.28%; p for Cochran Q<0.001). The CAM patients with a history of comorbidities other than diabetes (malignancies, transplant, or renal failure), mechanical ventilation due to COVID-19, pulmonary and cerebral mucormycosis, and those who only received medical treatment for mucormycosis had the highest mortality rate. Summary: Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is a major public health problem, particularly in developing countries. Severe COVID-19 infection, history of mechanical ventilation, early CAM, comorbidities other than diabetes (malignancies, transplant, or renal failure), pulmonary and rhino-orbito-cerebral mucormycosis, and delivering only medical treatment for mucormycosis were the worst prognostic factors in CAM patients. Identifying the mortality-related risk factors in CAM patients may help reduce the mortality rate by implementing optimized treatment approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s12281-022-00440-2.

Left ventricular thrombosis and endogenous endophthalmitis in the setting of COVID-19: A case report.

Aside from typical pneumonia, the coronavirus disease 2019 (COVID-19) has shown several extra-pulmonary manifestations. This study was done on a 66-year-old male patient who concomitantly had endogenous endophthalmitis and left ventricular thrombosis one month after being hospitalized due to COVID-19.

Effectiveness of Coronavirus Disease 2019 Vaccines in Preventing Infection, Hospital Admission, and Death: A Historical Cohort Study Using Iranian Registration Data During Vaccination Program.

Background: There are some concerns about the effectiveness of the inactivated and vector-based vaccines against severe acute respiratory syndrome coronavirus 2 in real-world settings with the emergence of new mutations, especially variants of concern. Data derived from administrative repositories during mass vaccination campaigns or programs are of interest to study vaccine effectiveness. Methods: Using 4-repository administrative data linkage, we conducted a historical cohort study on a target population of 1 882 148 inhabitants aged at least 18 years residing in southern Iran. Results: We estimated a 71.9% [95% confidence interval [CI], 70.7%-73.1%], 81.5% [95% CI, 79.5%-83.4%], 67.5% [95% CI, 59.5%-75.6%], and 86.4% [95% CI, 84.1%-88.8%] hospital admission reduction for those who received the full vaccination schedule of BBIBP-CorV (Sinopharm), ChAdOx1-S/nCoV-19 vaccine (AZD1222, Oxford-AstraZeneca), rAd26-rAd5 (Gam-COVID-Vac, Sputnik V), and BIV1-CovIran (COVIran Barekat) vaccines, respectively. A high reduction in mortality (at least 85%) was observed in all age subgroups of the fully immunized population. Conclusions: The pragmatic implementation of a vaccination plan including all available vaccine options in the Iranian population was associated with a significant reduction in coronavirus disease 2019 (COVID-19) detected infections as well as hospital admissions and deaths associated with COVID-19.

The association between helicobacter pylori infection and erosive gastroesophageal reflux disease; a cross-sectional study.

BACKGROUND: The association between H. pylori (Helicobacter pylori) infection and gastroesophageal reflux disease (GERD) is a complex and confusing subject. The aim of this study was to evaluate the association between helicobacter pylori infection and erosive gastroesophageal reflux disease. METHOD: In a cross-sectional study, all patients referred for endoscopy due to dyspepsia were enrolled. The diagnosis of erosive GERD was made by endoscopy. Patients with normal esophagus were selected as comparison group. Random gastric biopsies were taken from all participants to diagnose H. pylori infection. RESULT: In total, 1916 patients were included in this study, of whom 45.6% had GERD. The mean age (SD) was 42.95 (16.32). Overall, 1442 (75.3%) patients were positive for H. pylori infection. The frequency of H. pylori infection in mild GERD patients was higher than the severe GERD, but this difference was not significant (P = 0.214). Except for sociodemographic status (P < 0.001), other variables including gender, age, ethnicity, body mass index (BMI), smoking, and presence of hiatus hernia in patients had no significant association with the frequency of H. pylori infection. According to Robust Poisson regression models analysis, the association of H. pylori (PR 1.026; 95% CI 0.990-1.064; P = 0.158) and sociodemographic status were not significantly different between the two groups. But smoking, increased BMI, older age, presence of hiatus hernia, and peptic ulcer diseases were significantly associated with GERD compared with the non-GERD group. CONCLUSION: In our results, there was no association between H. pylori infection and erosive GERD. Further studies are recommended.

Serosurvey of hepatitis A virus and E virus infection among municipal sweepers working in the largest city in the south of Iran.

This study was conducted to determine the exposure rate of Hepatitis A and Hepatitis E viruses in urban solid waste collectors/sweepers in the south of Iran. The 385 samples (serums) were collected from Shiraz Municipality waste sweepers.. A questionnaire was used to gather data on their demographic and occupational characteristics, as well as their awareness of viral hepatitis disease. The viral seroprevalence was determined by commercial IgG ELISA kit. All participants were male, mean age of 41 ± 8 years. ELISA assay showed that all of them were positive for anti-HAV IgG. Also, 62 out of 385 individuals were positive for anti-HEV IgG. The statistical analysis showed that the frequency of HEV IgG antibody among age groups 20-30, 31-40, 41-50 and >50 years old had an increasing trend, 4.5%, 10.1%, 17.4%, and 36.7%, respectively, indicating age factor significance (p = .001). Based on some investigated factors including the duration of work experience, current and previous jobs, habitation, personal hygiene status, and knowledge on viral hepatitis diseasees/their transmission, there was no statistically significant difference between anti-HEV IgG positive versus negative sweepers. The results indicated a slighty higher frequency of anti-HAV and anti-HEV IgG among sweepers compared to other pre-investigated population. It doesn't seem that garbage collecting/sweeping could be a significant risk factor for HAV and HEV infection.

Spatial epidemiology of skin cancer in Iran: separating sun-exposed and non-sun-exposed parts of the body.

BACKGROUND: Skin cancer is among the most common cancer types with an increasing global trend of incidence rate. This study explores the spatial distribution of skin cancer, considering body sites exposed and not exposed to sunshine separately. METHODS: We used 4302 skin cancer cases recorded by Fars Cancer Registry in south-western Iran for over 6 years (2011-2017). The variables included in the study were patients' residence address, gender, age, report date, and final topographical code. The patients' addresses were geocoded to the counties of the study area. Skin cancer sites were categorized based on sun exposure in male and female cases. We used the empirical Bayesian smoothing approach to smooth the skin cancer incidence rate at the county level to remove any potential population size bias. Finally, Anselin's Local Moran's Index and Getis Ord G* were used to identify the clustered and high-risk skin cancer geographical areas. RESULTS: The incidence rates had an increasing trend from 14.28 per 100,000 people in 2011 to 17.87 per 100,000 people in 2016, however, it was decreased to 13.05 per 100,000 people in 2017. Out of 4302 patients with skin cancer, 2602 cases (60%) were male. The cancer cumulative incidence rate in males and females who were not exposed to sunshine was 7.80 and 14.18 per 100,000, respectively. The rates increased to 86.22 and 48.20 in males and females who were exposed to the sun. There were some high-risk spatial clusters of skin cancer in the study area. Further investigations are required to identify the underlying cause of the formation of these clusters. CONCLUSIONS: Patients exposed to sunshine, especially among the male group, experienced much higher rates of cancer occurrence as compared to unexposed individuals. With a heterogeneous spatial pattern, hotspots were identified in non-sun-exposed and sun-exposed categories in the study area. Researchers and policymakers can significantly benefit from the spatial analyses of skin cancer incidence. These analyses can provide useful and timely prevention policies as well as tailored monitoring techniques in high-risk regions.

Predictive determinants of overall survival among re-infected COVID-19 patients using the elastic-net regularized Cox proportional hazards model: a machine-learning algorithm.

BACKGROUND: Narrowing a large set of features to a smaller one can improve our understanding of the main risk factors for in-hospital mortality in patients with COVID-19. This study aimed to derive a parsimonious model for predicting overall survival (OS) among re-infected COVID-19 patients using machine-learning algorithms. METHODS: The retrospective data of 283 re-infected COVID-19 patients admitted to twenty-six medical centers (affiliated with Shiraz University of Medical Sciences) from 10 June to 26 December 2020 were reviewed and analyzed. An elastic-net regularized Cox proportional hazards (PH) regression and model approximation via backward elimination were utilized to optimize a predictive model of time to in-hospital death. The model was further reduced to its core features to maximize simplicity and generalizability. RESULTS: The empirical in-hospital mortality rate among the re-infected COVID-19 patients was 9.5%. In addition, the mortality rate among the intubated patients was 83.5%. Using the Kaplan-Meier approach, the OS (95% CI) rates for days 7, 14, and 21 were 87.5% (81.6-91.6%), 78.3% (65.0-87.0%), and 52.2% (20.3-76.7%), respectively. The elastic-net Cox PH regression retained 8 out of 35 candidate features of death. Transfer by Emergency Medical Services (EMS) (HR=3.90, 95% CI: 1.63-9.48), SpO2≤85% (HR=8.10, 95% CI: 2.97-22.00), increased serum creatinine (HR=1.85, 95% CI: 1.48-2.30), and increased white blood cells (WBC) count (HR=1.10, 95% CI: 1.03-1.15) were associated with higher in-hospital mortality rates in the re-infected COVID-19 patients. CONCLUSION: The results of the machine-learning analysis demonstrated that transfer by EMS, profound hypoxemia (SpO2≤85%), increased serum creatinine (more than 1.6 mg/dL), and increased WBC count (more than 8.5 (×109 cells/L)) reduced the OS of the re-infected COVID-19 patients. We recommend that future machine-learning studies should further investigate these relationships and the associated factors in these patients for a better prediction of OS.