Joint modeling of longitudinal and competing risks for assessing blood oxygen saturation and its association with survival outcomes in COVID-19 patients.

BACKGROUND: The objective of the present study is to evaluate the association between longitudinal and survival outcomes in the presence of competing risk events. To illustrate the application of joint modeling in clinical research, we assessed the blood oxygen saturation (SPO2) and its association with survival outcomes in coronavirus disease (COVID-19). MATERIALS AND METHODS: In this prospective cohort study, we followed 300 COVID-19 patients, who were diagnosed with severe COVID-19 in the Rohani Hospital in Babol, the north of Iran from October 22, 2020 to March 5, 2021, where death was the event of interest, surviving was the competing risk event and SPO2 was the longitudinal outcome. Joint modeling analyses were compared to separate analyses for these data. RESULT: The estimation of the association parameter in the joint modeling verified the association between longitudinal outcome SPO2 with survival outcome of death (Hazard Ratio (HR) = 0.33, P = 0.001) and the competing risk outcome of surviving (HR = 4.18, P < 0.001). Based on the joint modeling, longitudinal outcome (SPO2) decreased in hypertension patients (ß = -0.28, P = 0.581) and increased in those with a high level of SPO2 on admission (ß = 0.75, P = 0.03). Also, in the survival submodel in the joint model, the risk of death survival outcome increased in patients with diabetes comorbidity (HR = 4.38, P = 0.026). CONCLUSION: The association between longitudinal measurements of SPO2 and survival outcomes of COVID-19 confirms that SPO2 is an important indicator in this disease. Thus, the application of this joint model can provide useful clinical evidence in the different areas of medical sciences.

Association among general health, personality traits, and headache severity in patients with migraine.

Background: Because migraine is a common headache, finding ways to approach it better would be useful. So, studying the relation of dimensions of general health and personality types and pain severity in patients with migraine will be useful for fulfilling this aim. Methods: In this cross-sectional study, the number of patients with migraine headache studied in this study was 170. The checklists used in this study were migraine disability assessment (MIDAS), visual analog scale (VAS), Neuroticism-Extraversion-Openness (NEO FFI), and General Health Questionnaire (GHQ-28). Results: The average scores of general health dimensions in migraine sufferers with aura were higher than in migraine patients without aura. But this difference was significant only in the index of physical symptoms (P=0.02). There was a negative correlation between pain intensity and general health dimensions but it was not statistically significan. A positive correlation was observed between headache intensity and extroversion, which was significant (r=0.18 and P=0.01). The score of physical symptoms increases significantly with the increase of disability severity (P=0.007). Conclusion: According to the results, the severity of migraine disability, general health dimensions, and personality types in patients with and without Aura was not different. Also, general health dimensions and personality types were not associated with pain intensity and the severity of migraine disability.

Superinfected COVID-19 in a young patient with posterior reversible encephalopathy syndrome: A case report.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with central nervous system (CNS) symptoms usually related to autoregulatory cerebral failure and high blood pressure. Neuroimaging is critical to diagnosis. Neurological presentations of COVID-19 disease are categorized into CNS symptoms and peripheral nervous system (PNS) symptoms. The patient was a 15-year-old female with SARS-CoV-2 pneumonia who developed PRES with a typical clinical and radiological appearance. She was treated with dexamethasone, phenytoin, sodium valproate and remdesivir. The patient was discharged after recovery of symptoms and was in good general condition. It is recommended that in patients affected by COVID-19 with neurological symptoms, the PRES can be considered in the differential diagnosis.

Students' happiness and ranking of its dimensions in Mazandaran University of Science and Technology during the COVID-19 crisis.

BACKGROUND: Happiness and life satisfaction are positive indicators of mental health that should be considered by higher education and health officials. The aim of this study was to investigate the status of happiness and life satisfaction in students of Mazandaran University of Science and Technology during the outbreak of Coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This research is practical in terms of purpose and descriptive survey in terms of nature. The statistical population of this research was 2500 people. A total of 333 samples were selected by stratified random sampling. Data collection was performed using the standard Oxford Happiness Questionnaire and data analysis was performed by Friedman test, mean, and ranking. RESULTS: All dimensions of happiness of students of Mazandaran University of Science and Technology at the time of the outbreak of COVID-19 were in a relatively favorable situation. The dimensions of happiness were positive mood (3.57), positive energy (3.56), satisfaction (3.02), self-esteem (2.80), and life satisfaction (2.04). There was a significant difference between the dimensions of happiness and the variables of family income status (students with better financial status had a higher average), field of study (civil engineering students had a higher average), and gender (women had a higher average). No significant difference was found among the variables of marriage, educational level, semester, or rank in terms of several family children, with the dimensions of happiness. CONCLUSION: Examining the dimensions of students' happiness during the COVID-19 crisis will help the officials of the higher education system, in addition to planning to maintain the personal health and safety of students and curriculum appropriate to the time of crisis, and implement appropriate programs to maintain and promote the mental health and happiness of students.

Mistreatment with maggot therapy in diabetic foot ulcer causing an amputation.

Maggot therapy is one of the treatments used in diabetic foot ulcer management. But if we do not pay attention to the indications and contraindications of it, there might be a failure in the treatment.

Lyme neuroborreliosis: A case report.

Key Clinical Message: Lyme neuroborreliosis is the manifestation of Lyme borreliosis that impacts the nervous system. It gives rise to various neurological and psychiatric conditions, and its diagnosis is challenging. The timely administration of antibiotics is effective. Abstract: A male patient, aged 55, was admitted to the emergency department due to the sudden onset of tonic-clonic seizures. All standard laboratory examinations yielded unremarkable outcomes, except a favorable Wright and 2-mercaptoethanol test. The examination of cerebrospinal fluid revealed the presence of 380 white blood cells per milliliter. The protein level was also elevated, while the glucose level was within the normal range. The results of the serologic tests indicated the presence of both IgG and IgM antibodies to Borrelia burgdorferi. Following the administration of ceftriaxone, a significant improvement was observed in the patient's medical status, and he was subsequently discharged. Lyme neuroborreliosis is the manifestation of Lyme borreliosis that impacts the nervous system. It gives rise to various neurological and psychiatric conditions, and its diagnosis is challenging. The timely administration of antibiotics is effective in treating patients.

Anticoagulant therapy in COVID-19: A narrative review.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID-19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.

The Use of Remdesivir in Patients with COVID-19.

Remdesivir has appeared to be the most effective medication against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is broadly administered to coronavirus disease 2019 (COVID-19) patients around the world. Remdesivir is an RNA polymerase inhibitor with a broad spectrum of antiviral activities against RNA viruses in in-vitro and in-vivo models of SARSCoV, the Middle East respiratory syndrome (MERS), and SARS-CoV-2. Remdesivir is the first Food and Drug Administration (FDA) approved anti-SARS-CoV-2 treatment for adult and pediatric patients and has been used for not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death. However, questions have been raised about the value of remdesivir in treating COVID-19, and governing bodies worldwide have been hesitant to approve this medication. Nevertheless, in the context of the public health emergency and the urgent need for effective treatments for patients with COVID-19, remdesivir has been approved by several authorities worldwide. Here, we discuss the characteristics and applications of remdesivir, and various challenging studies with different outcomes about its efficacy are also reviewed.

Clinical misdiagnosis of influenza infection with a confusing clinical course: A case report.

A 32-year-old woman with a history of hypothyroidism and major depressive disorder was admitted with severe weakness and somnolence. She had tachycardia and hypotension, indicative of severe dehydration, and was treated with a vasopressor and sodium bicarbonate, but her clinical manifestations deteriorated. A high-resolution computed tomography (HRCT) scan showed a patchy ground glass appearance with interlobular septal thickening, suggesting pneumonia. Reverse transcription-polymerase chain reaction (RT-PCR) was requested for the influenza A virus (IAV), which was positive. The patient was treated with oseltamivir and discharged with improved clinical symptoms.

SARS-CoV-2 Omicron (B.1.1.529) Variant: A Challenge with COVID-19.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there have been multiple peaks of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus virus 2) infection, mainly due to the emergence of new variants, each with a new set of mutations in the viral genome, which have led to changes in the pathogenicity, transmissibility, and morbidity. The Omicron variant is the most recent variant of concern (VOC) to emerge and was recognized by the World Health Organization (WHO) on 26 November 2021. The Omicron lineage is phylogenetically distinct from earlier variants, including the previously dominant Delta SARS-CoV-2 variant. The reverse transcription-polymerase chain reaction (RT-PCR) test, rapid antigen assays, and chest computed tomography (CT) scans can help diagnose the Omicron variant. Furthermore, many agents are expected to have therapeutic benefits for those infected with the Omicron variant, including TriSb92, molnupiravir, nirmatrelvir, and their combination, corticosteroids, and interleukin-6 (IL-6) receptor blockers. Despite being milder than previous variants, the Omicron variant threatens many lives, particularly among the unvaccinated, due to its higher transmissibility, pathogenicity, and infectivity. Mounting evidence has reported the most common clinical manifestations of the Omicron variant to be fever, runny nose, sore throat, severe headache, and fatigue. This review summarizes the essential features of the Omicron variant, including its history, genome, transmissibility, clinical manifestations, diagnosis, management, and the effectiveness of existing vaccines against this VOC.

The role of cytokines and their antagonists in the treatment of COVID-19 patients.

The coronavirus disease 2019 (COVID-19) has various presentations, of which immune dysregulation or the so-called cytokine storm syndrome (COVID-CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID-19 infections, caused by the excessive release of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, tumour necrosis factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin-6 receptor blocker approved to treat severe COVID-19 infections.

A review of the potential neurological adverse events of COVID-19 vaccines.

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain-Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell's palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

Evaluation of Time-Varying Biomarkers in Mortality Outcome in COVID-19: an Application of Extended Cox Regression Model.

Background: COVID-19 pandemic has created many challenges for clinicians. The monitoring trend for laboratory biomarkers is helpful to provide additional information to determine the role of those in the severity status and death outcome. Objective: This article aimed to evaluate the time-varying biomarkers by LOWESS Plot, check the proportional hazard assumption, and use to extended Cox model if it is violated. Methods: In the retrospective study, we evaluated a total of 1641 samples of confirmed patients with COVID-19 from October until March 2021 and referred them to the central hospital of Ayatollah Rohani Hospital affiliated with Babol University of medical sciences, Iran. We measured four biomarkers AST, LDH, NLR, and lymphocyte in over the hospitalization to find out the influence of those on the rate of death of COVID-19 patients. Results: The standard Cox model suggested that all biomarkers were prognostic factors of death (AST: HR=2.89, P<0.001, Lymphocyte: HR=2.60, P=0.004, LDH: HR=2.60, P=0.006, NLR: HR=1.80, P<0.001). The additional evaluation showed that the PH assumption was not met for the NLR biomarker. NLR biomarkers had a significant time-varying effect, and its effect increase over time (HR(t)=exp (0.234+0.261×log(t)), p=0.001). While the main effect of NLR did not show any significant effect on death outcome (HR=1.26, P=0.097). Conclusion: The reversal of results between the Cox PH model and the extended Cox model provides insight into the value of considering time-varying covariates in the analysis, which can lead to misleading results otherwise.

Do we miss rare adverse events induced by COVID-19 vaccination?

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.

Tuberculosis arthritis of ankle: A case report.

Tuberculosis (TB) primarily involves the respiratory tract, but any organ in the body can be affected. In recent years, extrapulmonary TB cases have significantly increased due to the prevalence of immunocompromised patients. Here, we report a case of unilateral ankle arthritis due to Mycobacterium tuberculosis infection.

Fulminant hepatitis following COVID-19 vaccination: A case report.

The common side effects of COVID-19 vaccination were mostly self-restricted local reactions that quickly resolved. Nevertheless, rare autoimmune hepatitis cases have been reported in some vaccinated with mRNA COVID-19 vaccines. This article presents a young man who developed fulminant hepatitis a few days after vaccination with the first dose of the AstraZeneca COVID-19 vaccine. A 35-year-old man was admitted to our hospital with generalized weakness, abdominal pain, and jaundice. He received the first dose of the AstraZeneca COVID-19 vaccine 8 days earlier. He was admitted to the hospital with a chief complaint of abdominal pain. On admission and because of his high D-dimers, low platelet count, and low Fibrinogen level, vaccine-induced immune thrombosis thrombocytopenia was suspected, which was ruled out later. Then, after a surge in his liver function tests, decreasing platelet, and abnormal clotting tests, fulminant hepatitis was considered for this patient. Several bacterial, viral, and autoimmune etiologies were then suspected, with all ruled out. Thus, fulminant hepatitis secondary to his AstraZeneca COVID-19 vaccine was confirmed. Unfortunately, he died 3 days later of disseminated intravascular coagulopathy, after which a liver necropsy was performed, indicating drug/toxin-induced hepatitis.

Prognostic accuracy of inflammatory markers in predicting risk of ICU admission for COVID-19: application of time-dependent receiver operating characteristic curves.

OBJECTIVE: Intensive care unit (ICU) admission occurs at different times during hospitalization among patients with COVID-19. We aimed to evaluate the time-dependent receive operating characteristic (ROC) curve and area under the ROC curve, AUC(t), and accuracy of baseline levels of inflammatory markers C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in predicting time to an ICU admission event in patients with severe COVID-19 infection. METHODS: In this observational study, we evaluated 724 patients with confirmed severe COVID-19 referred to Ayatollah Rohani Hospital, affiliated with Babol University of Medical Sciences, Iran. RESULTS: The AUC(t) of CRP and NLR reached 0.741 (95% confidence interval [CI]: 0.661-0.820) and 0.690 (95% CI: 0.607-0.772), respectively, in the first 3 days after hospital admission. The optimal cutoff values of CRP and NLR for stratification of ICU admission outcomes in patients with severe COVID-19 were 78 mg/L and 5.13, respectively. The risk of ICU admission was significantly greater for patients with these cutoff values (CRP hazard ratio = 2.98; 95% CI: 1.58-5.62; NLR hazard ratio = 2.90; 95% CI: 1.45-5.77). CONCLUSIONS: Using time-dependent ROC curves, CRP and NLR values at hospital admission were important predictors of ICU admission. This approach is more efficient than using standard ROC curves.

COVID-19 vaccination challenges: A mini-review.

The emergence of SARS-CoV-2 has led to the infection of many people across the globe, over six million deaths, and has placed an unprecedented burden on public health worldwide. The pandemic has led to the high-speed development and production of vaccines against the COVID-19, as vaccines can end the pandemic. At the beginning of the program, vaccinations were initially targeted only at high-risk groups, such as the elderly, those with comorbidities, or healthcare workers. Although most of the mentioned populations have received the two recommended doses, limited resources have left many authorities with an effective vaccine undersupply. Therefore, policies have been implemented to manage the available doses of the vaccines more efficiently. As there is no universally agreed consensus on this topic, we discuss the different recommendations and guidelines regarding the time interval between the two vaccine doses and explain the different scenarios for applying the two doses.

Breakthrough SARS-CoV-2 infections after vaccination: a critical review.

At the beginning of the current pandemic, it was believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection would induce lifelong immunity and that reinfections would be unlikely. However, after several cases of reinfection were documented in previously infected patients, this was understood to be a false assumption, and this waning humoral immunity has raised significant concerns. Accordingly, long-term and durable vaccine-induced antibody protection against infection have also become a challenge, as several breakthroughs of COVID-19 infection have been identified in individuals who were fully vaccinated. This review discusses the current evidence on breakthrough COVID-19 infections occurring after vaccination.

Optimal cut points of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) in patients with COVID-19.

BACKGROUND: COVID19 patients may suffer from multiple cardiovascular complications. Recently, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) was a potentially independent risk factor for COVID-19 in-hospital death. The present study aimed to find new optimal cut points for NT-proBNP across censored survival failure time outcomes in hospitalized COVID-19 patients. RESULTS: This cohort study was conducted on 272 patients with COVID-19 whose initial records were recorded from March 2020 to July 2020. Demographic characteristics, clinical examinations, and laboratory measurements were collected at the beginning of the admission registered in the patient record system located in the hospital. We used the maximally selected rank statistics to determine the optimal cut points for NT-proBNP (the most significant split based on the standardized log-rank test). Survival time was defined as the days from hospital admission to discharge day. In this cohort study, two optimal cut points for NT-proBNP were 331 (pg/mL) and 11,126 (pg/mL) based on a survival model. The adjusted HR of NT-proBNP for in-hospital death was 3.41 (95% CI: 1.22-9.51, P = 0.02) for medium against low category, and 3.84 (95% CI: 1.30-11.57, P = 0.01) for high in comparison with low group. CONCLUSIONS: We reported a dramatically increased concentration of NT-proBNP among COVID-19 patients without heart failure in both severe and non-severe cases. Moreover, our study showed that a high level of NT-proBNP was highly associated with the prolonged survival time of patients with COVID-19. NT-proBNP is a strong prognostic indicator of in-hospital death in the second week of admission.