Medication safety in a pandemic: A multicentre point prevalence study of QTc monitoring of hydroxychloroquine for COVID-19.

WHAT IS KNOWN AND OBJECTIVE: A pandemic can strain all aspects of the healthcare system, including the ability to monitor the safety of medication use. Reviewing the adequacy of medication safety practices during the COVID-19 pandemic is critical to informing responses to future pandemics. The purpose of this study was to evaluate medication safety practices at a height of both COVID-19 cases and hydroxychloroquine use. METHODS: This was a multicentre observational point prevalence study. Adult inpatients receiving hydroxychloroquine for COVID-19 between March 22 and 28, 2020 were included. The primary outcome was the percentage of patients receiving appropriate QTc monitoring. Secondary outcomes included QTc prolongation, early discontinuation of hydroxychloroquine and ventricular arrhythmias. RESULTS AND DISCUSSION: A total of 59% (167/284) of patients treated with hydroxychloroquine received appropriate QTc monitoring. QTc prolongation occurred in 25%. Hydroxychloroquine was prematurely discontinued in 1.4% of patients, all due to QTc prolongation. Ventricular arrhythmia occurred in 1.1%. WHAT IS NEW AND CONCLUSION: Medication safety practices were suboptimal with regard to hydroxychloroquine monitoring at the height of the COVID-19 pandemic. Preparation for future pandemics should devote considerable attention to medication safety.

Intravenous N-Acetylcysteine in Management of COVID-19: A Case Series.

A novel coronavirus, severe acute respiratory syndrome coronavirus-2, was isolated from patients' lower respiratory tracts in December 2019. As of May 19, 2021, there were over 33 million reported infections and almost 600,000 deaths in the United States. The infection, coronavirus disease-19 (COVID-19), can lead to cytokine storm, with elevations in interleukin-6 (IL-6), IL-10, tumor necrosis factor-α, nuclear factor-kappaB (NF-kappaB), and glutathione reductase. NF-kappaB activation is necessary for further transcription of other pro-inflammatory markers. Glutathione may play a role in modulation of NF-kappaB activation and elevated glutathione reductase may indicate glutathione depletion. Administration of N-acetylcysteine (NAC) may replenish spent glutathione and attenuate over-activation of NF-kappaB. This retrospective case series included 10 patients who were COVID-19 positive and received intravenous NAC in an attempt to attenuate the cytokine storm. Patients' outcomes were graded based on the World Health Organization symptom severity scale from 0, no evidence of infection, to 8, death. Overall, the median WHO Scale prior to NAC was 6.5, and increased by day seven, which indicated clinical worsening. This retrospective case series showed no benefit of NAC; however, further studies are needed to elucidate if differences in drug regimens would lead to positive results.

Impact of Tocilizumab on Clinical Outcomes in COVID-19-Associated Cytokine Release Syndrome: A Single-Center Experience.

BACKGROUND: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. METHODS: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. RESULTS: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. CONCLUSION: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

Early clinical outcomes with tocilizumab for severe COVID-19: a two-centre retrospective study.

Severe COVID-19 (coronavirus disease 2019) is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an interleukin-6 (IL-6) inhibitor effective in treating CRS secondary to chimeric antigen receptor T-cell (CAR T-cell) therapy. The efficacy of tocilizumab in treating COVID-19 is unknown. This was a retrospective cohort study conducted at two hospitals in northern New Jersey (USA). All patients treated with tocilizumab for confirmed or suspected COVID-19 between 10 March 2020 and 9 April 2020 at the study sites were included. The primary endpoint was clinical improvement on Day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. A total of 45 severe and critically ill patients treated with tocilizumab for COVID-19 were evaluated. Of the 45 patients, 11 (24.4%), 22 (48.9%) and 12 (26.7%) patients improved, had no change or worsened by Day 7 after treatment, respectively. Lower white blood cell count and lactate dehydrogenase at the time of drug administration as well as shorter time from supplemental oxygen initiation to dosing were significantly associated with clinical improvement in the univariate analysis. In conclusion, tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with COVID-19.

Implementation of a QTc-interval monitoring protocol by pharmacists to decrease cardiac risk in at-risk patients in an acute care inpatient psychiatric facility.

INTRODUCTION: Many medications commonly prescribed in psychiatric hospitals can cause QTc-interval prolongation, increasing a patient's risk for torsades de pointes and sudden cardiac death. There is little guidance in the literature to determine when an electrocardiogram (ECG) and QTc-interval monitoring should be performed. The primary end point was improvement of the appropriateness of ECGs and QTc-interval monitoring of at-risk psychiatric inpatients at Barnabas Health Behavioral Health Center (BHBH) and Monmouth Medical Center (MMC) following implementation of a standardized monitoring protocol. The secondary end point was the number of pharmacist-specific interventions at site BHBH only. METHODS: Patients who met the inclusion criteria were assessed using a standardized QTc-prolongation assessment algorithm for ECG appropriateness. A retrospective analysis of a control group (no protocol) from January 1, 2016, to July 17, 2017, was compared with a prospective analysis of the intervention group (with protocol) from December 11, 2017, to March 11, 2018. RESULTS: At BHBH, appropriate ECG utilization increased 25.5% after implementation of a standardized protocol (P = .0172) and appropriate omission of ECG utilization improved by 26% (P < .00001). At MMC, appropriate ECGs decreased by 5%, and appropriate ECG omissions increased by 28%, neither of which were statistically significant (P = 1.0 and P = .3142, respectively). There was an increase in overall pharmacist monitoring. DISCUSSION: The study demonstrated that pharmacist involvement in ECG and QTc-interval monitoring utilizing a uniform protocol may improve the appropriateness of ECG and QTc-interval monitoring in patients in an acute care inpatient psychiatric hospital.

miR-10b is a prognostic marker in clear cell renal cell carcinoma.

AIMS: Clear cell renal cell carcinoma (ccRCC) is the most common adult kidney cancer. It is an aggressive tumour with unpredictable outcome. The currently used clinical parameters are not always accurate for predicting disease behaviour. miR-10b is dysregulated in different malignancies including RCC. METHODS: We assessed the clinical utility of miR-10b as a prognostic marker in 250 patients with primary ccRCC. We examined the correlation between miR-10b and clinicopathological parameters. We compared miR-10b expression among different RCC subtypes and normal kidney tissue. RESULTS: We observed a stepwise decrease of miR-10b expression from normal kidney to primary ccRCC and a further decrease from primary to metastatic RCC. miR-10b expression was significantly lower in stages III/IV compared with stages I/II (p=0.038). Using a binary cut-off, miR-10b-positive patients had significantly longer disease-free survival (HR=0.47, CI 0.28 to 0.79, p=0.004). In the subgroup of patients with tumour size >4 cm, higher miR-10b expression was associated with significant longer disease-free and overall survival (p=0.001 and p=0.036, respectively). miR-10b was significantly downregulated in ccRCC compared with normal kidney (p<0.0001), and oncocytoma (p=0.031). It was also downregulated in chromophobe RCC. In addition, we identified a number of miR-10b-predicted targets and pathways that are involved in tumourigenesis. CONCLUSIONS: Our data point to miR-10b as a promising prognostic marker in ccRCC with potential therapeutic applications.

Tinzaparin reduces health care resource use for anticoagulation in hemodialysis.

Anticoagulation is required during hemodialysis to prevent thrombus formation within the extracorporeal circuit. The low-molecular-weight heparin tinzaparin is more expensive than unfractionated heparin (UFH) in Canada but more convenient to administer. We conducted a time-and-motion study to test the hypothesis that tinzaparin may reduce nursing time and total health care costs compared with UFH. Data on health care resource use associated with anticoagulation during hemodialysis for chronic renal failure were collected at an academic hospital in Quebec. Nursing time was recorded for 8 nurses performing 16 dialysis sessions for 4 patients receiving tinzaparin and 4 receiving UFH (2 dialysis sessions per patient). Nurses had ≥ 1 year of experience supervising hemodialysis. We estimated total annual costs of nursing time and health care resources (anticoagulants, medical supplies, and laboratory testing) associated with anticoagulation. In sensitivity analyses, drug costs were varied ± 30% of their base-case values. Estimated annual nursing times per patient were 0.8 vs. 11.5 hours in the first year and 0.6 vs. 10.2 hours in subsequent years for tinzaparin vs. UFH, respectively. Annual drug costs per patient were CAD 898.56 for tinzaparin and 546.75 for UFH. Estimated total annual costs were CAD 1061.03 vs. 1012.71 in the first year and CAD 917.75 vs. 895.23 in subsequent years for tinzaparin vs. UFH, respectively. Use of tinzaparin was cost saving relative to UFH if tinzaparin price was reduced 30%. Most of the price differential between tinzaparin and UFH is offset by substantial time savings to nephrology nurses.