Navigating the evolving landscape of HFpEF management: A detailed look at key ACC/AHA/ESC guideline updates.

Heart failure, a growing concern in the United States, significantly impacts both morbidity and mortality. Classified by ejection fraction, heart failure with preserved ejection fraction (HFpEF) now accounts for half of all cases and is steadily rising. Unlike its counterpart, heart failure with reduced ejection fraction (HFrEF), HFpEF lacks clear management guidelines. Recognizing this critical gap, we aim to review existing recommendations and formulate effective management strategies for HFpEF.

Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus.

In 2005, exenatide became the first approved glucagon-like peptide-1 receptor agonist (GLP-1 RA) for type 2 diabetes mellitus (T2DM). Since then, numerous GLP-1 RAs have been approved, including tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, which was approved in 2022. This class of drugs is considered safe with no hypoglycemia risk, making it a common second-line choice after metformin for treating T2DM. Various considerations can make selecting and switching between different GLP-1 RAs challenging. Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.

Adherence to Advisory Committee on Immunization Practices in diabetes mellitus patients in Saudi Arabia: A multicenter retrospective study.

BACKGROUND: Patients with diabetes mellitus (DM) are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications. The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices (CDC/ACIP) issued immunization re-commendations to protect this patient population. AIM: To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate. METHODS: An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey. RESULTS: Among participants, 10.01% (n = 71) had never received any vaccine, while 85.89% (n = 609) received at least one dose of the coronavirus disease 2019 (COVID-19) vaccine, and 34.83% (n = 247) had received the annual influenza vaccine. Only 2.96% (n = 21), 2.11% (n = 15), and 1.12% (n = 8) received herpes zoster, tetanus, diphtheria, and pertussis (Tdap), and human papillomavirus (HPV) vaccines, respectively. For patients with DM in Saudi Arabia, the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, site of care, income level, DM-related hospitalization history, residency site, hemoglobin A1c (HbA1c) level, and health sector type can significantly influence the vaccination rate in patients with DM. Among non-vaccinated patients with DM, the most reported barriers were lack of knowledge and fear of side effects. This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM. CONCLUSION: In Saudi Arabia, patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, the site of care, income level, DM-related hospitalization history, residency site, HbA1c level, and health sector type can significantly influence the vaccination rate in patients with DM.

Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study.

BACKGROUND: Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone's clinical and safety outcomes compared to methylprednisolone. METHODS: A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient's age and MODS within 24 h of ICU admission. RESULTS: After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. CONCLUSION: Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Clonidine safety and effectiveness in the management of suspected paroxysmal sympathetic hyperactivity post-traumatic brain injury: A retrospective cohort study.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. In addition, TBI may cause paroxysmal sympathetic hyperactivity (PSH), which is associated with poor clinical outcomes. This study aimed to evaluate the safety and effectiveness of clonidine in patients with TBI and suspected PSH. METHODS: A retrospective cohort study for critically ill patients with TBI with suspected PSH admitted to intensive care units (ICUs) from 1 May 2016 to 31 January 2020 at a tertiary academic medical center. Eligible patients were categorized based on clonidine use during their ICU stay (Clonidine group vs. Control group). The primary outcome was the improvement in functional outcomes during ICU stay, defined by a delta Glasgow Coma Score (GCS). Secondary outcomes included ICU and hospital length of stay, heart rate variation, and 90-day mortality. RESULTS: A total of 2915 patients were screened, of which 169 were included. Based on multiple regression analysis, patients who received clonidine showed better improvement in functional outcomes by a higher mean delta GCS than patients who did not (Beta Coeff. 0.41; CI: 0.07 - 0.74; P = 0.02). In addition, the patient's GCS upon ICU discharge and IV opioids requirement on day three were higher in the clonidine group than control (beta coefficient (95% CI): 0.18 (0.03, 0.32); p = 0.02 and beta coefficient (95% CI): 1.38 (0.24, 2.52); p = 0.02, respectively). No statistical differences were observed in any of the other secondary outcomes after adjusting for confounders. CONCLUSION: This study found that patients who received clonidine had better functional outcomes during their ICU stay, as shown by their delta GCS than those who did not. Other outcomes were similar between the groups. More data are needed to explore the role of clonidine in patients with TBI with suspected PSH.

Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19-A multicenter cohort study.

Background: Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients. Methods: A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate. Results: A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87-1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00-0.47), p = 0.05 and beta coefficient 0.16 (95% CI -0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03]. Conclusion: The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.

Alternatives to Hydrocortisone for Hemodynamic Support in Septic Shock Management Due to Medication Shortage.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Septic shock is when initial fluid resuscitation fails to increase the mean atrial pressure to greater than or equal to 65 mm Hg. The 2021 Surviving Sepsis Campaign guidelines recommend corticosteroids for vasopressor and fluid-refractory septic shock patients. Medication shortages can arise, and their etiologies include natural disasters, quality control issues, and manufacturing discontinuation. The U.S. Food and Drug Administration and the American Society of Health-System Pharmacists announced a shortage of IV hydrocortisone. Methylprednisolone and dexamethasone are considered therapeutic alternatives to hydrocortisone. This commentary aims to guide clinicians on the alternative to hydrocortisone among septic shock patients due to medication shortage.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Effect of Broad-Spectrum Antibiotic De-escalation on Critically Ill Patient Outcomes: A Retrospective Cohort Study.

PURPOSE: Antibiotic de-escalation (ADE) in critically ill patients is controversial. Previous studies mainly focused on mortality; however, data are lacking about superinfection. Therefore, we aimed to identify the impact of ADE versus continuation of therapy on superinfections rate and other outcomes in critically ill patients. METHODS: This was a two-center retrospective cohort study of adults initiated on broad-spectrum antibiotics in the intensive care unit (ICU) for ≥ 48 h. The primary outcome was the superinfection rate. Secondary outcomes included 30-day infection recurrence, ICU and hospital length of stay, and mortality. RESULTS: 250 patients were included, 125 in each group (ADE group and continuation group). Broad spectrum antibiotic discontinuation occurred at a mean of 7.2 ± 5.2 days in the ADE arm vs. 10.3 ± 7.7 in the continuation arm (P value = 0.001). Superinfection was numerically lower in the ADE group (6.4% vs. 10.4%; P = 0.254), but the difference was not significant. Additionally, the ADE group had shorter days to infection recurrence (P = 0.045) but a longer hospital stay (26 (14-46) vs. 21 (10-36) days; P = 0.016) and a longer ICU stay (14 (6-23) vs. 8 (4-16) days; P = 0.002). CONCLUSION: No significant differences were found in superinfection rates among ICU patients whose broad-spectrum antibiotics were de-escalated versus patients whose antibiotics were continued. Future research into the association between rapid diagnostics with antibiotic de-escalation in the setting of high resistance is warranted.

Adefovir Dipivoxil as a Therapeutic Candidate for Medullary Thyroid Carcinoma: Targeting RET and STAT3 Proto-Oncogenes.

Aberrant gene expression is often linked to the progression of various cancers, making the targeting of oncogene transcriptional activation a potential strategy to control tumor growth and development. The RET proto-oncogene's gain-of-function mutation is a major cause of medullary thyroid carcinoma (MTC), which is part of multiple endocrine neoplasia type 2 (MEN2) syndrome. In this study, we used a cell-based bioluminescence reporter system driven by the RET promoter to screen for small molecules that potentially suppress the RET gene transcription. We identified adefovir dipivoxil as a transcriptional inhibitor of the RET gene, which suppressed endogenous RET protein expression in MTC TT cells. Adefovir dipivoxil also interfered with STAT3 phosphorylation and showed high affinity to bind to STAT3. Additionally, it inhibited RET-dependent TT cell proliferation and increased apoptosis. These results demonstrate the potential of cell-based screening assays in identifying transcriptional inhibitors for other oncogenes.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors Use among Heart Failure Patients and the Role of Pharmacists in Early Initiation of Therapy.

Heart failure (HF) is a growing major public health and economic concern in the United States and worldwide. Heart failure mortality rates can be as high as 75% despite advances in therapies. HF is expected to be the fastest growing among all cardiovascular diseases, with HF-associated direct medical costs projected to nearly double over the next 10 years. Hospital admissions, re-admission, and medical cost are a huge burden to the healthcare system, and this is estimated to have increased gradually over the past decades despite the available advances in HF treatment and prevention. Many heart failure therapies have shown improvement in terms of mortality, morbidity, and symptomatic management. Guideline-directed medical therapy (GDMT) for heart failure has proven its ability to reduce morbidity and mortality by 66%. GDMT is recommended to be used among all HF patients when appropriate. In recent years, two new drug classes, angiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, were approved by the United States Food and Drug Administration (US FDA) for the management of heart failure. The exact mechanism by which the SGLT-2 inhibitors attenuate the inflammatory process remains unclear. Several mechanisms have been suggested related to the cardiovascular benefit of SGLT-2 inhibitors, including a reduction in inflammation, improvement in natriuresis/diuresis, and promotion of the use of ketones as a secondary energy source. Clinical data showed that SGLT-2 inhibitors have morbidity and mortality benefits within 30 days of initiation. Studies have proven that clinical pharmacists practicing in HF inpatient and outpatient settings resulted in a reduction of HF hospitalization and an increase in the uptake of GDMT by initiating or up-titrating GDMT agents as well as providing patient education.

Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice.

In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran. DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin. The immediate reversal of these agents can be indicated in an emergency setting. Antithrombotic reversal recommendations are still in development. Vitamin K and prothrombin complex concentrate (PCCs) can be used for warfarin reversal. Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively. Protamine sulfate is the solely approved reversal agent for unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.

Evaluation of Rocuronium Continuous Infusion in Critically Ill Patients During the COVID-19 Pandemic and Drug Shortages.

Background: Limited data exist to support the use of rocuronium continuous infusions in the intensive care unit (ICU). Objective: To evaluate the dosing and monitoring of adult patients who received rocuronium for hypoxemic respiratory failure during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This was a retrospective, single-center study from March 1, 2020 to May 31, 2020. We identified all adult patients admitted to any ICU who received rocuronium via continuous infusion. Patients were excluded if they received rocuronium for <6 hours. The main outcome of this study was to determine the median rocuronium maintenance continuous infusion rate in the ICU. Secondary outcomes of this study included the initial continuous infusion rate, duration of therapy, cumulative dose, frequency and median of rocuronium boluses, time to resolution of neuromuscular blockade, and the relationship between the hourly administration rates of rocuronium and train-of-four (TOF) assessments. Results: Seventy-one patients and 97 paralytic infusions were included. Fifty-nine patients (83%) were positive for SARS CoV-2. Of the 97 rocuronium infusions, the median dose at initiation was 3 (3-5) mcg/kg/min and duration of infusion was 45 (23.6-92.5) hours. The median continuous infusion maintenance rate was 4.3 (2.8-7.2) mcg/kg/min. There was a negligible correlation between the dose of rocuronium and the TOF results (r = .04). A total of 1775 TOFs were assessed, of which 46.2% were over-paralyzed, 35.7% well-paralyzed, and 18.1% under-paralyzed. Conclusions: The initial and maintenance infusion doses in our analysis were lower than what have been previously referenced.

The 2022 human monkeypox outbreak: Clinical review and management guidance.

PURPOSE: The objective of this clinical review is to provide an overview of antiviral therapies for monkeypox treatment and summarize the role of vaccines in monkeypox prevention. SUMMARY: The human monkeypox virus is a double-stranded DNA virus of the Orthopoxvirus genus of the Poxviridae family. The estimated case fatality rate for monkeypox ranges between 0% and 11%. The first human monkeypox infection was reportedly due to an unidentified animal reservoir. Per the Centers for Disease Control and Prevention, isolation and infection control procedures should be followed in the care of those infected with monkeypox virus. Monkeypox virus infection symptoms include rash, fever, chills, headache, muscle aches, backache, and fatigue that may progress to exhaustion. Severe complications such as encephalitis, pneumonia, and retropharyngeal abscess could appear in immunocompromised or critically ill patients. There are currently no specific Food and Drug Administration (FDA)-approved therapies for monkeypox. As with most viral infections, supportive care is the backbone of monkeypox clinical management. However, therapies effective for smallpox, such as cidofovir, brincidofovir, and tecovirimat, have previously been reported to be effective in the management of monkeypox. Pre- and postexposure prophylaxis to prevent monkeypox transmission are recommended in the US for those at high risk for disease transmission. CONCLUSION: There are no FDA-approved treatments for monkeypox infection. Surveillance and detection of monkeypox among high-risk populations should be implemented to help understand the epidemiology of this disease.

Systolic Blood Pressure Variability When Transitioning From Intravenous to Enteral Antihypertensive Agents in Patients With Hemorrhagic Strokes.

Background/Objective: Systolic blood pressure variability (SBPV) in patients with intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is associated with an increased risk of acute kidney injury (AKI) and mortality. SBPV is a strong predictor of poor functional outcomes in patients with ICH. Intravenous (IV) antihypertensive agents are commonly used to achieve sustained target blood pressure goals; however, this is not a feasible long-term option. The transition from IV to enteral antihypertensives is not yet well established in patients with ICH and SAH. This study aimed to assess the effect of the number of antihypertensive agents and overlap time during the transition period from IV to enteral route on SBPV in patients with ICH and SAH. Methods: This retrospective single-center study was conducted at a tertiary teaching hospital in Riyadh, Saudi Arabia. Data were extracted from electronic medical records after obtaining Institutional Review Board approval. Patients were included if they were >18 years old, admitted with spontaneous ICH or SAH, and received continuous infusion antihypertensives prior to transitioning to the enteral route. The major outcome was the effect of the number of antihypertensive agents and overlap time on SBPV during the transition process. Minor outcomes included the effect of the number of antihypertensive agents and overlap time on heart rate variability and the incidence of AKI on day 7. Results: After the screening, we included 102 patients. Based on our regression model, the number of enteral antihypertensive agents upon transitioning from IV to enteral antihypertensive therapy had no effect on SBPV in the intensive care unit (ICU) among our patients (p-value = 0.274). However, the prolonged overlap was associated with reduced SBPV in the ICU (p-value = 0.012). No differences were observed between the groups in heart rate variation or AKI rate. Conclusions: In patients with ICH and SAH, prolonged overlap of enteral antihypertensive agents to overlap with intravenous antihypertensive therapy may result in lower SBPV. This finding needs to be confirmed on a larger scale with more robust study designs for patients with ICH and SAH.

Kidney Function Assessment in African American Patients: A Narrative Review for Pharmacists.

Recent recognitions of longstanding societal inequity in kidney function assessments have prompted the call to eliminate race as part of the algorithm to assess estimated glomerular filtration rate (eGFR). Previous equations for eGFR estimation adopted race as part of the calculation. Incorporating race within eGFR equations results in overestimating and underestimating Black and nonblack patients, respectively. The inclusion of race is controversial. In September 2021, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) combined task force recommended estimating the kidney function without using a race variable. The task force endorsed race-free creatinine-cystatin C equations to be more accurate than the creatinine-only equations. Before the application of NKF-ASN revised recommendations, major healthcare disparities influenced daily clinical practice. Those disparities include the delay in initiating medications that have reanl or cardio-protective effects, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and angiotensin-converting enzyme inhibitors (ACEIs). Clinical judgment should be employed when dose adjusting medications. Combining the eGFR with other clinical assessment tools such as urinary output, the expanded use of confirmatory tests, and the eGFR trend is suggested for a better kidney function assessment. Additionally, creatinine-cystatin C is recommended when feasible, and when institutions have the laboratory abilities.

The safety and effectiveness of tocilizumab in older adult critically ill patients with COVID-19: a multicenter, cohort study.

OBJECTIVES: Evidence supports tocilizumab (TCZ) benefit and safety in adult patients with severe COVID-19. However, its effectiveness in critically ill older adult patients remains questionable. Thus, the study aimed to evaluate the safety and effectiveness of TCZ in older critically ill patients with COVID-19. METHODS: A multicenter, retrospective study for all critically ill older adults (aged ≥65 years) with confirmed COVID-19 infection and admitted to the intensive care units (ICUs). Eligible patients were categorized into two groups based on TCZ use during ICU stay (control vs TCZ). Propensity score (PS) matching was used (1:1 ratio) based on the selected criteria. The primary outcome was the in-hospital mortality. RESULTS: A total of 368 critically ill older adult patients were included in the study. Fifty one patients (13.8%) received TCZ. The in-hospital mortality was lower in the TCZ group (HR 0.41; 95% CI 0.22-0.76, P-value = 0.005). Patients who received TCZ had lower odds of respiratory failure requiring mechanical ventilation (OR [95% CI]: 0.32 [0.10-0.98], P-value = 0.04). No statistically significant differences were found between the two groups for 30-days mortality, ventilator-free days, length of stay, and complications during ICU stay. CONCLUSION: Tocilizumab use in critically ill older adult patients with COVID-19 is associated with lower in-hospital mortality and a similar safety profile.

Colistin Loading Dose in Septic Patients with Gram Negative Infections.

Purpose: Intravenous (IV) colistin is commonly used to treat multidrug-resistant gram-negative infections. It is primarily eliminated renally and may induce acute kidney injury (AKI) at a rate of up to 53%. Consequently, septic patients who require colistin administration have an additional risk of developing AKI. The aim of this study is to investigate clinical failure and AKI predictors for septic patients treated with IV colistin. Methods: This retrospective cohort study was conducted at a tertiary teaching hospital in Saudi Arabia. Adult septic patients with suspected or confirmed gram-negative infections who received colistin admitted to the hospital between May 2016 and December 2020 were screened after obtaining IRB approval. AKI was defined based on the AKI Network criteria. We investigated the incidence of clinical failure based on colistin dosing and AKI risk factors, such as the development of septic shock, severity of illness, and medication co-administration using a multiple logistic regression model. Results: After screening 163 patients, 103 patients were included in the analysis. No difference was observed between the colistin dosing strategies for clinical failure. Of the included predictors, development of septic shock (OR: 3.75; 95% CI 1.18-13.15), carbapenem co-administration (OR, 3.96; 95% CI, 1.134-15.57) were associated with an increased risk of AKI. The other factors were not significant predictors. Conclusion: Clinical failure was not affected by colistin dosing strategies in our cohort of patients with sepsis. Moreover, the co-administration of carbapenems and the development of septic shock may increase the risk of inducing AKI in adult septic patients treated with IV colistin. Further studies are required to confirm these findings.