Effects of nebulized hypertonic saline on inflammatory mediators in patients with severe COVID-19 pneumonia: A double-blinded randomized controlled trial.

INTRODUCTION: An exaggerated immune response is considered the most important aspect of COVID-19 pathogenesis. Hypertonic saline (HS) has shown promise in combating inflammation in several respiratory diseases. We investigated the effects of nebulized HS on clinical symptoms and inflammatory status in patients with severe novel coronavirus infection (COVID-19) pneumonia. MATERIALS AND METHODS: We randomly assigned 60 adults admitted to the intensive care unit (ICU) due to severe COVID-19 pneumonia to the experimental (received nebulized 5% saline) and control (received nebulized distilled water) groups. All interventions were applied 4 times daily for 5 days. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and other clinical factors from venous blood were evaluated before and after intervention application. Mortality rate, intubation rate, and durations of ICU and hospital stay were also compared between groups. RESULTS: The levels of TNF-α (MD: -21.35 [-32.29, -10.40], P = 0.000) and IL-6 (-9.94 [-18.86, -1.02], P = 0.003) were lower in the experimental group compared to the control group after applying the interventions. The levels of white blood cell count, PO2, and serum sodium were also statistically significant differences between groups. However, we did not observe significant differences in terms of hospitalization durations and mortality rates. CONCLUSION: Nebulization of HS in patients with severe COVID-19 pneumonia appears to be effective in reducing inflammation, but does not appear to affect intubation rates, mortality, hospitalization, or length of stay in ICU.

Effectiveness of a Supportive Program on Caregiver Burden of Families Caring for Patients on Invasive Mechanical Ventilation at Home: An Experimental Study.

The prevalence of patients on mechanical ventilation who are being supported at home is increasing. Due to these patients' complex and chronic conditions, the subjective burden on their family caregivers increases after discharge. The aim of this study was to evaluate the effectiveness of a supportive home care program on the caregiver burden of families caring for patients on invasive mechanical ventilation at home. Sixty patients hospitalized in three university-affiliated hospitals in Tehran, Iran between 7/2020 and 8/2021 were randomly assigned to one of two groups: A supportive home care program, and routine hospital education. The supportive home care program included six educational sessions delivered in the hospital before discharge, and home visits and continued education after discharge. Caregiver burden was measured using the Zarit Burden Interview. Results showed that caregiver burden increased significantly (p ≥ .001) after discharge without the supportive home care program intervention. Follow-up by nurses after discharge is essential to reduce the psychological burden of caring for patients on invasive mechanical ventilation at home.

Determine phenotypical patterns of resistance to antibiotics in COVID-19 patients with associated bacterial infection: largest medical center in Iran.

Background and Objectives: Antibacterial resistance (AMR) is a serious threat and major concern, especially in developing countries. Therefore, we aimed to determine phenotypical patterns of resistance to antibiotics in COVID-19 patients with associated bacterial infection in intensive care units. Materials and Methods: In this cross-sectional study, 6524 COVID-19 patients admitted for more than 48 h in the ICUs of Imam Khomeini Complex Hospital (IKCH) in Tehran from March 2020 to January 2022 were included in the study with initial diagnosis of COVID-19 (PCR test and chest imaging). Data were collected regarding severity of the illness, primary reason for ICU admission, presence of risk factors, presence of infection, length of ICU and hospital stay, microbial type, and antibiotic resistance. In this study, the pattern of antibiotic resistance was determined using the Kirby-Bauer disk diffusion method. Results: In this study, 439 (37.5%) were ventilator-related events (VAEs), and 46% of all hospitalized patients had an underlying disease. The most common microorganisms in COVID-19 patients were carbapenem resistant Klebsiella pneumoniae (KPCs) (31.6%), Escherichia coli (E. coli) (15.8%), and Acinetobacter baumannii (A. baumannii) (15.7%), respectively. Prevalence of vancomycin-resistant enterococci (VRE) and KPCs were 88% and 82%, respectively. Conclusion: A study on AMR surveillance is the need of the hour as it will help centers to generate local antibiograms that will further help formulate national data. It will guide doctors to choose the appropriate empiric treatment, and these studies will be the basis for establishing antimicrobial surveillance and monitoring and regulating of the use of antimicrobials.

Can addressing family education improve outcomes of patients under home invasive mechanical ventilation? A randomized controlled clinical trial.

The use of home mechanical ventilation is increasingly developing. The present study aimed to examine the effect of a family-centered training program on patients under home invasive mechanical ventilation. A total of 60 adult patients under invasive mechanical ventilation were selected and randomly allocated into two groups. The supportive home care program consisting of six training sessions using a teach-back technique and follow up training at home. The rate of hospital readmission and mortality in the intervention group was significantly lower than the control group(P = .02 and P = .03, respectively). Moreover, the home caregivers' level of knowledge in the intervention group was significantly higher than that of the control group(P = 0/000). In addition, implementing the intervention effectively increased home caregivers' ability of functional skills. Therefore, comprehensive preparation of the patient and family before discharge and coherent support and continuity of care after discharge with the effective presence of nurses.

Safety of megadose meropenem in the empirical treatment of nosocomial sepsis: a pilot randomized clinical trial.

Objective: To evaluate the safety of megadose meropenem as empirical treatment of nosocomial sepsis. Materials & methods: Critically ill patients diagnosed with sepsis received either high-dose (2 g every 8 h) or megadose (4 g every 8 h) meropenem as an intravenous infusion over 3 h. Results: A total of 23 patients with nosocomial sepsis were eligible and included in the megadose (n = 11) or high-dose (n = 12) group. No treatment-related adverse events were observed during a 14-day follow-up. Clinical response was also comparable between the groups. Conclusion: Megadose meropenem may be considered for empirical treatment of nosocomial sepsis without serious concern regarding its safety.

As resistance to antibiotics is increasing among microbes, rational use of these drugs is important both in the community and in hospitals. Many infections with resistant microorganisms may be fatal. For a long time, carbapenems have been the last resort for treatment of resistant microorganisms. Unfortunately, resistance to these drugs is increasing. It appears that use of higher doses of antibiotics may help in some cases. However, the potential harm caused by higher doses is a problem. In this primary study, higher doses of meropenem, a common carbapenem, were found to be safe.

Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

Does the rubella immunoglobulin G affect the severity of COVID- 19? : Rubella immunoglobulin G and COVID- 19.

OBJECTIVE & AIM: The coronavirus disease, so far (COVID-19) has brought about millions of infections and fatalities throughout the world. Our aim was to determine the correlation between rubella IGG titers with the severity COVID-19.  MATERIALS & METHODS: This study was conducted among COVID-19 confirmed patients over 18 years of age. The disease severity levels were categorized by WHO interim guidance. The rubella-specific IgG antibody-titer spectrum was measured (within first 48 h of hospitalization) by enzyme-linked immunosorbent assay (ELISA). RESULT: In a study of 46 inpatients with varying COVID-19 disease severity (mild, moderate, severe, and critical), we observed a negative correlation between rubella IgG antibody titers and COVID-19 severity (P-Value = 0.017), There was an interaction between COVID-19 vaccination history and rubella IGG on severity COVID-19 (P-Value = 0.0015). There was an interaction between age group under 44 years (including national measles- rubella (MR) vaccination in Iran) and rubella IGG titers on severity COVID-19 too (p-value = 0.014). CONCLUSION: In conclusion, MR vaccination seems to have a positive effect in reducing the severity of the disease, emphasizing that, the important and separate effect of the IGG rubella (due to natural or extrinsic immunity) titers is determining.

Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II.

BACKGROUND: Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. METHODS: Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. RESULTS: All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). CONCLUSIONS: For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287 . IRCT, IRCT20180619040147N6. Registered 04/01/2021.

The outcome of using intravenous immunoglobulin (IVIG) in critically ill COVID-19 patients': a retrospective, multi-centric cohort study.

BACKGROUND: During the COVID-19 pandemic, different treatments have been used in critically ill patients. Using intravenous immunoglobulin (IVIG) has been suggested in various studies as an effective option. Our study aims to access the efficacy of IVIG in critically ill COVID-19 patients. METHODS: In this retrospective matched cohort study, records of three tertiary centers with a large number of COVID-19 admissions were evaluated and used. Based on treatment options, patients were divided into two groups, standard COVID-19 treatment (109 patients) and IVIG treatment (74 patients) patients. Also, the effect of IVIG in different dosages was evaluated. Patients with IVIG treatment were divided into three groups of low (0.25 gr/kg), medium (0.5 gr/kg), and high (1 gr/kg) dose. Data analysis was performed using an independent t test and one-way analysis of variance (ANOVA) to compare the outcomes between two groups, including duration of hospitalization, intensive care unit (ICU) length of stay, and mortality rate. RESULTS: The duration of hospitalization in the IVIG group was significantly longer than standard treatment (13.74 days vs. 11.10 days, p < 0.05). There was no significant difference between the two groups in ICU length of stay, the number of intubated patients, and duration of mechanical ventilation (p > 0.05). Also, initial outcomes in IVIG subgroups were compared separately with the standard treatment group. The results indicated that only the duration of hospitalization in the IVIG subgroup with medium dose is significantly longer than the standard treatment group (p < 0.01). CONCLUSION: Our data indicate that the use of IVIG in critically ill COVID-19 patients could not be beneficial, based on no remarkable differences in duration of hospitalization, ICU length of stay, duration of mechanical ventilation, and even mortality rate.

Deciding When to Intubate a COVID-19 Patient.

Background: The SARS-CoV-2 pandemic is one of the most significant challenges for healthcare providers, particularly in the critical care setting. The timing of intubation in COVID-19 patients seems to be challenging. Therefore, we aimed to investigate how it may have a survival benefit, and we determined which clinical characteristics were associated with outcomes. Methods: This cross-sectional study was conducted in the Imam Khomeini Hospital Complex. We randomly selected patients admitted to intensive care units and, based on intubation status, categorized them into three subgroups (early, late, and not intubated). Early intubation is defined as intubation within 48 hours of ICU admission, and late intubation is defined as intubation after 48 hours of ICU admission. Results: Early-intubated patients were more likely to have dyspnea than late-intubated patients, and late-intubated patients had a higher mean heart rate than early-intubated patients. The neutrophil/lymphocyte ratio was significantly (P < 0.05) lower in not-intubated patients than in other patients. There was no difference in NLR between early- and late-intubated patients. Mean serum creatine phosphokinase and troponin I levels were higher in late-intubated patients than in early- and not-intubated patients. Early-intubated patients had a lower ROX index than late-intubated patients. Patients with higher scores of APACHE 2, respiratory rates, and neutrophil to lymphocyte ratio were more likely to be intubated. Increasing APACHE and SOFA scores were associated with decreased odds of survival. Conclusions: There were no statistically significant differences in total mortality between early- and late-intubated patients. APACHE 2 scores, NLR, RR, and history of ischemic heart disease are some of the appropriate predictors of intubation. Higher respiratory rates (tachypnea) can be an indicator of early intubation. The ROX index is one of the most sensitive and capable tools for predicting intubation. Intubation status is a potent predictor of in-hospital mortality.

A contextual needs assessment of families with home invasive mechanical ventilation patients: A qualitative study.

OBJECTIVES: With the advancement of technology the number of patients surviving critical illness has increased. Home mechanical ventilation (HMV) is a growing option for patients requiring long-term mechanical ventilation. Caring for these patients is demanding and challenging. The aim of this study was to explore family caregivers'(carers) needs when providing care to adult patients under HMV from the perspective of nurses, home care attendants, and the caregivers themselves. METHODS: Overall, 15 participants (nine carers, three home nurses, and three home care attendants) were selected by purposive sampling. Data were collected by in-depth semi-structured interviews and structured observation. Finally, data were analyzed through conventional content analysis with MAXQDA software. RESULTS: Three categories of carers'needs were identified, including educational needs (basic and emergencies), psychological needs, and economic needs. In addition, since the needs, feelings, and views of caregivers change over time, the noted needs were divided into three periods: Pre-discharge preparation, initial transition from hospital to home, and appropriate long-term follow-up. CONCLUSION: The study results showed that the families of patients under invasive HMV require a standard discharge plan based on their care needs, financial concerns, and psychological screening before discharge as well as a suitable long-term follow-up plan in collaboration with a multidisciplinary treatment team, insurance providers, and home care services.

When Technology Enters at Home: The Challenges of Home Health Care Providers in a Developing Country.

The number of patients with chronic diseases requiring invasive mechanical ventilation at home is increasing. Thus, identifying the challenges of this valuable type of care can be an elective step for achieving health-related goals. This study was conducted to determine the challenges faced by home health care providers. Three themes emerged from the data analysis: (1) hospital-based challenges with 2 subthemes: the family unpreparedness for home care and the lack of continuous education; (2) home health care agency challenges with 2 subthemes: home health care workers and the deficiency in organizational policies; and (3) economic challenges. Three themes of hospital-related challenges, home health care agency challenges, and economic challenges that emerged in the study showed that support from the insurance system, improvement of home care agency policies, and holistic care for patients through a multidisciplinary team approach are essential for addressing the current challenges of care for patients under invasive mechanical ventilation at home.