Medication Changes and Diagnosis of New Chronic Illnesses in COVID-19 Intensive Care Unit Survivors

Background Currently, there is limited literature on the impact of the COVID-19 infection on medications and medical conditions in COVID-19 intensive care unit (ICU) survivors. Our study is, to our knowledge, the first multicenter study to describe the prevalence of new medical conditions and medication changes at hospital discharge in COVID-19 ICU survivors. Objective To determine the number of medical conditions and medications at hospital admission compared to at hospital discharge in COVID-19 ICU survivors. Methods Retrospective multicenter observational study (7 ICUs) evaluated new medical conditions and medication changes at hospital discharge in patients with COVID-19 infection admitted to an ICU between March 1, 2020, to March 1, 2021. Patient and hospital characteristics, baseline and hospital discharge medication and medical conditions, ICU and hospital length of stay, and Charlson comorbidity index were collected. Descriptive statistics were used to describe patient characteristics and number and type of medical conditions and medications. Paired t-test was used to compare number of medical conditions and medications from hospital discharge to admission. Results Of the 973 COVID-19 ICU survivors, 67.4% had at least one new medical condition and 88.2% had at least one medication change. Median number of medical conditions (increased from 3 to 4, P < .0001) and medications (increased from 5 to 8, P < .0001) increased from admission to discharge. Most common new medical conditions at discharge were pulmonary disorders, venous thromboembolism, psychiatric disorders, infection, and diabetes. Most common therapeutic categories associated with medication change were cardiology, gastroenterology, pain, hematology, and endocrinology. Conclusion and Relevance Our study found that the number of medical conditions and medications increased from hospital admission to discharge. Our results provide additional data to help guide providers on using targeted approaches to manage medications and diseases in COVID-19 ICU survivors after hospital discharge.

Site-Specific and Country-of-Origin Labeling for Pharmaceutical Manufacturing

There is increasing concern about the quality of pharmaceuticals, especially generics made in Asia. Popular books and news reports have the public questioning the quality of pharmaceuticals. Recalls and import bans shake confidence in medications, particularly for active pharmaceutical ingredients and finished dosage forms made outside the United States. The Food and Drug Administration uses geography to allocate resources for manufacturing surveillance. Site of manufacturing labeling, including the country, could be linked to the facility’s quality score to assess the risk of poor quality. Clinicians should advocate for legal and regulatory changes to increase the transparency of pharmaceutical manufacturing of products.

Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge

Background: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. Objective: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. Results: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). Conclusions and Relevance: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

Evaluation of Continuous Inhaled Epoprostenol in the Treatment of Acute Respiratory Distress Syndrome, Including Patients With SARS-CoV-2 Infection

Background Acute respiratory distress syndrome (ARDS) management is primarily supportive. Pulmonary vasodilators, such as inhaled epoprostenol (iEPO), have been shown to improve PaO2:FiO2 (PF) and are used as adjunctive therapy. Objective To identify the positive response rate and variables associated with response to iEPO in adults with ARDS. A positive response to iEPO was defined as a 10% improvement in PF within 6 hours. Methods This retrospective study included adults with ARDS treated with iEPO. The primary endpoint was the variables associated with a positive response to iEPO. Secondary endpoints were positive response rate and the change in PF and SpO2:FiO2 within 6 hours. Statistical analysis included multivariable regression. Results Three hundred thirty-one patients were included. As baseline PF increased, the odds of responding to iEPO decreased (odds ratio [OR], 0.752, 95% CI, 0.69-0.819, p < 0.001). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related ARDS (OR 0.478, 95% CI, 0.281-0.814, p = 0.007) was associated with decreased odds of a positive response to iEPO. The total population had a 68.3% positive response rate to iEPO. SARS-CoV-2-related ARDS and non-SARS-CoV-2-related ARDS had a 59.5% and 72.7% positive response rate, respectively. iEPO significantly improved PF (71 vs 95, P < 0.001) in the whole population. Conclusion and Relevance iEPO was associated with a positive effect in a majority of moderate-to-severe ARDS patients, including patients with SARS-CoV-2-related ARDS. Lower baseline PF and non-SARS-CoV-2-related ARDS were significantly associated with a positive response to iEPO. The ability to predict which patients will respond to iEPO can facilitate better utilization.

Finerenone: A Novel Mineralocorticoid Receptor Antagonist for Cardiorenal Protection in CKD and T2DM

Objective: To describe the pharmacology, clinical and safety evidence, and relevance to clinical practice of finerenone. Data Sources: A literature search was conducted utilizing PubMed, MEDLINE, and clinicaltrials.gov with search terms of “finerenone” and “BAY94-8862.” Study Selection and Data Extraction All available studies with human participants in English were considered. Studies were included if they investigated drug pharmacology, efficacy, and safety information. Data Synthesis In addition to standard of care with a renin-angiotensin system inhibitor (RASi), finerenone lowered the risk of kidney disease progression (17.8% vs 21.1%) in patients with type 2 diabetes mellitus and chronic kidney disease compared to placebo. Similarly, finerenone reduced cardiovascular risk in patients with type 2 diabetes mellitus and chronic kidney disease compared to placebo (12.4% vs 14.2%). Relevance to Patient Care and Clinical Practice It is anticipated that finerenone will be added to therapy after a RASi and a sodium-glucose cotransporter-2 inhibitor, as tolerated, based on adverse events and potassium levels. Conclusions Finerenone offers a unique approach to further delay the progression of chronic kidney disease in patients with type 2 diabetes mellitus. It also provides another option for patients who cannot tolerate RASi or sodium-glucose cotransporter-2 inhibitors.

Impact of Defibrotide in the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

Finally, an FDA Approval for an Immunization Against COVID-19: Hope on the Horizon

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018—October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

Evidence Needed for Efficacy of Antidepressant Medications Among Patients With Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) experience pain from inflammation, joint destruction, and neuropathy. Antidepressants may play a role among patients with RA and depression, fibromyalgia, or neuropathy to achieve desired outcomes. This commentary evaluated evidence for medications individually and identified important variables for future research. While we await the results of well-designed studies, a trial of duloxetine or milnacipran may be considered for patients with remnant pain and RA remission. Research is needed to evaluate the efficacy and safety of serotonin–norepinephrine reuptake inhibitors and tricyclic antidepressants in patients with RA and associated comorbid conditions.

Safety and Efficacy of Various Intravenous Insulin Infusion Rates in Patients With and Without Diabetes Presenting With Hypertriglyceridemia

Background The use of IV insulin infusions in the acute management of hypertriglyceridemia has only been evaluated in small observational studies and case reports. Objective To evaluate the safety and efficacy of IV insulin infusions in the acute management of hypertriglyceridemia. Methods This was a retrospective chart review of adult patients who received an IV insulin infusion for the acute management of hypertriglyceridemia. The primary efficacy and safety outcomes were the number of patients who achieved a triglyceride level <500 mg/dL and experienced hypoglycemia (<70 mg/dL), respectively. A subgroup analysis was performed to compare outcomes between patients with and without diabetes, in addition to the IV insulin infusion rate received. Results In the total population (n = 51), there were no statistically significant differences between the insulin intensity groups in the number of patients who achieved TG levels <500 mg/dL. Compared to patients with a past medical history of diabetes, more patients without a past medical history of diabetes achieved triglyceride levels <500 mg/dL (14% vs 53%, respectively, P < 0.001). The number of hypoglycemic events observed in patients with and without a past medical history of diabetes were 5 (14%) and 4 (27%), respectively ( P = 0.023). Conclusion and Relevance Our findings suggest that patients who present with lower initial TG levels are more likely to achieve TG levels <500 mg/dL. To minimize the risk of hypoglycemia providers should consider prescribing a concomitant dextrose infusion and limiting IV insulin infusion rates ≤ 0.075 units/kg/h.