Application of Mixture and Non-mixture Cure Models in Survival Analysis of Patients With COVID-19.

Background Due to the emergence of new COVID-19 mutations and an increase in re-infection rates, it has become an important priority for the medical community to identify the factors affecting the short- and long-term survival of patients. This study aimed to determine the risk factors of short- and long-term survival in patients with COVID-19 based on mixture and non-mixture cure models. Methodology In this study, the data of 880 patients with COVID-19 confirmed with polymerase chain reaction in Fereydunshahr city (Isfahan, Iran) from February 20, 2020, to December 21, 2021, were gathered, and the vital status of these patients was followed for at least one year. Due to the high rate of censoring, mixture and non-mixture cure models were applied to estimate the survival. Akaike information criterion values were used to evaluate the fit of the models. Results In this study, the mean age of the patients was 48.9 ± 21.23 years, and the estimated survival rates on the first day, the fourth day, the first week, the first month, and at one year were 0.997, 0.982, 0.973, 0.936, and 0.928, respectively. Among the parametric models, the log-logistic mixed cure model with the logit link, which showed the lowest Akaike information criterion value, demonstrated the best fit. The variables of age and prescribed medication type were significant predictors of long-term survival, while occupation was influential in the short-term survival of patients. Conclusions According to the results of this study, it can be concluded that elderly patients should observe health protocols more strictly and consider receiving booster vaccine doses. The log-logistic cure model with a logit link can be used for survival analysis in COVID-19 patients, a fraction of whom have long-term survival.

Disseminated mycobacterium genavense infection with central nervous system involvement in an HIV patient: a case report and literature review.

BACKGROUND: Immunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients. CASE PRESENTATION: We describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses. CONCLUSION: The diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system.

Managing Hepatotoxicity Caused by Anti-tuberculosis Drugs: A Comparative Study of Approaches.

BACKGROUND: Tuberculosis (TB) is one of the oldest and most well-known diseases that has been associated with humans for many years and remains a global health challenge today. Timely diagnosis and proper treatment are crucial for controlling and preventing the spread of the disease. While anti-TB drugs offer many benefits, inadequate monitoring can lead to a range of side effects, including hepatotoxicity, which is a major concern and can cause treatment discontinuation. The aim of this study was to determine the approach to the hepatotoxicity of anti-TB drugs and to investigate potential relationships between demographic factors, underlying medical conditions, and successful retreatment outcomes for hepatotoxicity induced by anti-TB drugs. METHODS: For this study, we reviewed the medical records of patients who experienced hepatotoxicity due to anti-TB treatment and were admitted to the infectious ward of Imam Khomeini Hospital between April 2015 and February 2019. The data were collected using a questionnaire. RESULTS: The findings indicated that the female gender, weight loss at the beginning of hospitalization, hepatitis C virus, hepatitis B virus (HBV), heart disease, and high levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) at the beginning of hepatotoxicity are risk factors for failure to the retreatment of hepatotoxicity. There were two different approaches to the anti-TB retreatment regimen. The first approach involved gradually starting the drugs in full dose, while the second approach encompassed starting the drugs in the minimum dose and then increasing to the maximum dose. The results demonstrated no significant difference between the two approaches to managing hepatotoxicity induced by anti-TB drugs. CONCLUSION: Drug-induced hepatotoxicity is a common occurrence that often results in treatment discontinuation. Understanding the prevalence of this complication and identifying appropriate methods of rechallenge treatment is crucial to reducing complications and mortality rates.

Vitamin D deficiency and oral candidiasis in patients with HIV infection: A case‒control study.

BACKGROUND: Oral candidiasis is a common opportunistic infection in patients with human immunodeficiency virus (HIV). In addition, most of these patients suffer from vitamin D deficiency. This study aimed to investigate the association between vitamin D levels and oral candidiasis in patients with HIV infection. METHODS: This case‒control study was conducted on HIV-infected patients. Cases were patients with oral candidiasis diagnosed based on physical examinations. Controls were age- and sex-matched individuals without oral candidiasis. The levels of 25-OH vitamin D and other laboratory markers (CD4 count and viral load) were compared between the case and control groups. RESULTS: A total of 104 cases and 102 controls were included in the study. The cases had significantly lower 25-OH vitamin D3 levels (MD = 33.86 ng/mL, 95% CI= (31.85, 35.87), P < 0.001) and CD4 counts (MD = 267.48 cells/mm3, 95% CI= (189.55, 345.41), P < 0.001) than the controls. In addition, viral load was significantly higher in cases than in controls (MD = 7.03 × 105 copies/mL, 95% CI= (4.46 × 105, 9.61 × 105), P < 0.001). The multivariate logistic regression analysis revealed that educational status (OR = 0.032, 95% CI= (0.002, 0.100), P < 0.001), current HAART (OR = 0.005, 95% CI= (0.001, 0.014), P < 0.001), history of oral candidiasis (OR = 20.114, 95% CI= (18.135, 21.957), P < 0.001), CD4 count (OR = 0.004, 95% CI= (0.001, 0.006), P < 0.001), viral load (OR = 12.181, 95% CI= (1.108, 133.392), P < 0.001), and vitamin D level (OR = 0.011, 95% CI= (0.008, 0.015), P < 0.001) were significantly associated with the risk of developing oral candidiasis. CONCLUSIONS: Based on the findings, most patients with HIV infection suffer from vitamin D deficiency, especially those with oral candidiasis. Hypovitaminosis D was significantly associated with an increased risk of oral candidiasis. Thus, vitamin D supplementation may assist HIV-positive patients in improving their oral health and preventing oral candidiasis.

Tenofovir alafenamide plus dolutegravir as a switch strategy in HIV-infected patients: a pilot randomized controlled trial.

BACKGROUND: Currently, two-drug antiretroviral regimens are emerging fields in life-long treatment in people living with HIV. OBJECTIVES: This randomized non-inferiority open-label controlled trial was designed to compare the 48-week efficacy and safety of tenofovir alafenamide plus dolutegravir versus the standard triple therapy in virologically suppressed people living with HIV. To the best of our knowledge this combination has not been studied before. METHODS: This open-label randomized controlled trial was conducted in treatment-experienced people with HIV who had HIV-RNA < 47 copies/mL for at least two years. Patients received either tenofovir alafenamide plus dolutegravir combination (26 patients) or a standard three-drug regimen (29 patients). The primary outcome was the proportion of patients maintaining HIV-RNA < 47 copies/mL during 48 weeks, and the secondary outcomes were CD4 cell count changes, the adherence rate, and adverse drug reactions, all over 48 weeks of study. RESULTS: HIV viral load remained undetectable (HIV-RNA < 47 copies/mL) during the 48 weeks of the study in both arms. The absolute CD4 cell count change was not significant between the two groups. The overall proportion of adverse effects in each group was comparable. The rate of adherence to treatment was acceptable in both groups, and no significant difference was observed. CONCLUSIONS: Treatment simplification with tenofovir alafenamide plus dolutegravir regimen as maintenance therapy was non-inferior in terms of efficacy and safety compared to the standard triple therapy. Comparing efficacy of antiretroviral therapy.

Identification of Mycobacterium tuberculosis in pulmonary and extrapulmonary specimens of Iranian hospitalized patients during 2017-2021.

Background: Tuberculosis (TB) is one of the most serious public health problems worldwide which is a chronic infectious disease and is still one of the major challenges for developing countries. This study was undertaken to identify Mycobacterium TB (MTB) in clinical specimens in hospitalized patients. Methods: The study was carried out on specimens from pulmonary and extrapulmonary suspected TB patients that were admitted to one of the largest tertiary hospitals located in Tehran, Iran from 2017 to 2021. The GeneXpert MTB/rifampin (RIF) method was applied to detect MTB and RIF resistance. Characteristics of demography, clinical features, and lifestyle were obtained from medical case records registered in the hospital. Results: Of 957 specimens, 92 (9.61%) were found positive for TB by GeneXpert assay. Of positive samples, 72 (78.26%) were considered pulmonary TB, and 20 (21.73%) of them are associated with extrapulmonary involvement. Four (4.3%) positive TB cases were categorized as rifampicin-resistant. Conclusion: This study showed a relatively high incidence rate of TB in distinct types of specimens in Iranian hospitalized patients but a low level of RIF resistance.

Spontaneous Loculated Pneumomediastinum in a COVID-19-Infected Patient.

While we are still learning about COVID-19 affecting people, older persons and persons with underlying diseases such as high blood pressure, heart disease, and diabetes mellitus (DM) appear to develop serious illness and more complications often than others. In this report, we presented a patient with spontaneous pneumomediastinum after COVID-19. The patient was a 61-year-old man with a history of DM, hypertension, and heart failure, who has been infected with COVID-19. The patient was diagnosed with COVID-19 based on RT-PCR analysis of nasopharyngeal samples, and chest X-ray showed patchy infiltration upper and lower lobes bilaterally. By day 4, imaging was repeated, performed due to exacerbation of pleuritic chest pain, decreased O2 saturation (80%), and coughing that revealed multiple ground-glass opacities bilaterally, and interlobular septal thickening with emphysema in most of the left upper lobe and a small part of right upper lobe which led to severe spontaneous left pneumomediastinum and parenchymal consolidation was also observed. The combination of a chest tube, antibiotics (vancomycin 1 gr/bid and meropenem 1 g/bid), and antiviral (hydroxychloroquine 200 mg/bid and atazanavir 300 mg/daily) was prescribed, and continued treatment with antiviral and appropriate care for pneumomediastinum was successful. Spontaneous pneumomediastinum in the context of COVID-19 should be considered as a prognostic factor in favor of worsening diseases.

Rapid Detection Test for COVID-19 among Healthcare Workers and the Role of Personal Protective Equipment.

BACKGROUND: In this study, we assessed the prevalence of positive rapid detection test (RDT) among healthcare workers (HCWs) and evaluated the role of personal protective equipment (PPE) and knowledge of the pandemic. METHODS: In a cross-sectional study conducted between August 2020 and October 2020 in a tertiary referral center (Tehran, Iran), we enrolled 117 physicians, nurses, and other HCWs (OHCWs)-aides, helpers, and medical waste handlers-regularly working in coronavirus disease 2019 (COVID-19) wards. The RDT kit was utilized to reveal recent infection; data on demographics, PPE use and availability, and knowledge of the pandemic was collected through pre-defined questionnaires. RESULTS: Overall, 24.8% (95% CI: 16.8-32.7%) of HCWs had positive RDTs. The more PPE was available and used, the less the chance of positive RDT was (OR: 0.63 [0.44-0.91], P = 0.014 and 0.63 [0.41-0.96], P = 0.030). The same was true for the knowledge of prevention and adhering to preventive rules (OR: 0.44 [0.24-0.81], P = 0.008 and 0.47 [0.25-0.89], P = 0.020). OHCWs had the highest prevalence of positive RDT, while they had more shifts per month, less accessibility to PPE, and less knowledge of the pandemic than physicians. CONCLUSION: The findings of this study suggest that HCWs should have a thorough knowledge of the pandemic along with using PPE properly and rationally. Furthermore, adhering to preventive regulations plays a crucial role in HCWs' safety. It is also noteworthy that shifts should be arranged logically to manage exposures, with a special attention being paid to OHCWs.

Efficacy of a multiple-indication antiviral herbal drug (Saliravira®) for COVID-19 outpatients: A pre-clinical and randomized clinical trial study.

BACKGROUND: The scientific researches on COVID-19 pandemic topics are headed to an explosion of scientific literature. Despite these global efforts, the efficient treatment of patients is an in-progress challenge. Based on a meta-study of published shreds of evidence about compounds and their botanic sources in the last six decades, a novel multiple-indication herbal compound (Saliravira®) has been developed. Based on the antiviral, anti-inflammatory, and immune-enhancing properties of its ingredients, we hypothesized that Saliravira® has the potential to act as an antiviral agent, accelerate treatment, and reduce undesirable effects of COVID-19. METHODS: In this randomized, controlled, open-label clinical trial, COVID-19 outpatients were included by RT-PCR test or diagnosis of physicians according to the symptoms. Participants were randomly divided into intervention and control groups to receive Saliravira® package plus routine treatments of COVID-19 or routine treatments of COVID-19 alone, respectively. Saliravira® package includes tablets, nasal-sinuses spray, oral-pharynx spray, and inhaler drops. The treatment was for 10 days and followed up till 23 days after admission. RESULTS: On the 8th day, the "mean reduction rates" of viral load of the patients in the intervention group was 50% lower compared to the control group with a p-value < 0.05. The improvement of 10 out of 14 COVID-19 symptoms in the intervention group was significantly accelerated. The mean treatment duration of patients in the intervention group was 4.9 days less than the control group. In addition, no patients in the intervention group were hospitalized compared to 28% of the control group needed to be hospitalized.

Comparing efficacy and safety of tocilizumab and methylprednisolone in the treatment of patients with severe COVID-19.

OBJECTIVES: This study was designed to compare the efficacy and safety of methylprednisolone and tocilizumab in the treatment of patients with severe COVID-19. METHODS: During a prospective cohort study, hospitalized patients with severe COVID-19 received intravenous methylprednisolone (250-500 mg daily up to three doses), weight-based tocilizumab (maximum 800 mg, one or two doses as daily interval) or dexamethasone (8 mg daily). The primary outcome was time to onset of clinical response. Secondary outcomes were improvement rate of oxygen saturation and CRP, need for ICU admission, duration of hospitalization and 28-day mortality. During study, adverse events of the treatments were recorded. RESULTS: Although the difference was not statistically significant (p = 0.090), clinical response occurred faster in the tocilizumab group than other groups (10 vs. 16 days). Clinical response was detected in 74.19%, 81.25%, and 60% of patients in the methylprednisolone, tocilizumab, and dexamethasone groups respectively (p = 0.238). Based on the Cox regression analysis and considering dexamethasone as the reference group, HR (95% CI) of clinical response was 1.08 (0.65-1.79) and 1.46 (0.89-2.39) in the methylprednisolone and tocilizumab groups respectively. Improvement rate of oxygen saturation and CRP was not significantly different between the groups (p = 0.791 and p = 0.372 respectively). Also need for ICU admission and 28-day mortality was comparable between the groups (p = 0.176 and p = 0.143 respectively). Compared with methylprednisolone, tocilizumab caused more sleep disturbances (p = 0.019). Other adverse events were comparable among patients in the groups. CONCLUSION: When or where access to tocilizumab is a problem, methylprednisolone may be considered as an alternative for the treatment of patients with severe COVID-19.

The Persistence Time of SARS-CoV-2 RNA in Hospitalized COVID-19 Patients: A Prospective Study.

BACKGROUND: In late December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), spread to almost all countries worldwide. The outbreak of this virus has been confirmed on 19th February, 2020, in Iran. OBJECTIVE: The aim of this study was to investigate the time of viral RNA clearance in swab and serum samples of COVID-19 patients having received different medications. We also evaluated different factors that may affect viral RNA persistence in patients infected by SARS-CoV-2. METHODS: In March 2020, twenty-one hospitalized COVID-19 patients participated in this prospective study. All patients received antiviral agents in their routine care. Throat swabs and blood samples were obtained from all patients in different intervals, including day 3 or 5, day 7, day 10, and finally, 14 days after the first positive real-time RT-PCR (rRT-PCT) test. RESULTS: The median time from the symptom onset (SO) to the first negative rRT-PCR results for throat swabs and serum samples of COVID-19 patients was 18 and 14 days, respectively. These times were more significant in patients with lymphopenia, oxygen saturation ≤ 90%, and comorbidity. CONCLUSION: This preliminary study highlights that SASR-CoV-2 RNA was not detectable in the upper respiratory tract for longer than three weeks. In addition, SARS-CoV-2 may persist for a long period of time in the respiratory than in the serum samples. This study supports the idea that in limited resource settings, the patients should be tested earlier than three weeks for discharge management.

An Update to Enterococcal Bacteremia: Epidemiology, Resistance, and Outcome.

BACKGROUND: An increase in resistant gram-positive cocci, especially enterococci, requires an epidemiologic re-assay and its results may affect empirical treatments for these infections. OBJECTIVE: In this study, we investigated the microbial epidemiology and resistance pattern of enterococcal bacteremia. METHODS: This study was a cross-sectional study that investigated all cases of positive blood cultures with Enterococcus spp. at a tertiary referral colligates hospital in Tehran in 2018. RESULTS: Enterococcus spp. was isolated from blood cultures of a total of 73 patients. Most of the patients were male i.e: 42 (57.7%). The mean age of the patients was 58.8 (±18.8) years. Hospital- acquired infection was the most prevalent type of infection involving enterococcal bacteremia (80.8%) compared with community-acquired (6.7%) and the health care-associated one (12.3%). Renal failure and cancer were the most underlying disease in E. faecalis and E. faecium, respectively. Mortality for Vancomycin-resistant enterococci (VRE) was approximately two times more than the sensitive ones. Between the dead/alive groups, the following items were significantly different (P.Value<0.05): Vancomycin resistance for enterococcus isolated, immunodeficiency as an underlying disease, Mechanical ventilation, hospitalization period, and the empiric regimen. CONCLUSION: Increased antibiotic-resistant strains, especially Vancomycin-resistant enterococci (VRE), pose a serious threat to the general public, especially hospitalized patients, causing an increase in mortality. Surveillance of microorganisms and antimicrobial resistance is a crucial part of an efficient health care system.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.

BACKGROUND: The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19. METHODS: We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events. RESULTS: The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss. CONCLUSION: Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO2 < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.