Retrospective Study Evaluating Effect of Voxelotor Treatment on Acute Care Utilization during the Peak of COVID-19

Introduction In sickle cell disease (SCD), the polymerization of deoxygenated HbS fundamentally alters the structure of the erythrocyte, producing the sickle cell that is characteristic of the disease. Clinical manifestations often perceived in patients suffering from SCD include vaso-occlusion, anemia, and hemolysis. Due to these sequelae, patients frequent the emergency room (ER), urgent care clinic, and hospital. Voxelotor, an oral medication approved by the Food and Drug Administration (FDA) in 2019 for the treatment of SCD, directly targets the pathophysiology of SCD by inhibiting deoxygenated HbS polymerization. Results of the Phase III HOPE trial indicate that the drug can increase hemoglobin levels and reduce markers of hemolysis as well as the incidence of worsening anemia in patients with SCD (Vichinsky et al. N Engl J Med 2019). The COVID-19 pandemic has posed several challenges for patients with SCD in 2020. Amid the pandemic, patients continued to seek out acute medical care, including care in the ER, urgent care clinics, and hospital. The aim of this study was to determine whether utilization of acute medical care differed for patients who received voxelotor before and after therapy in 2020. We also evaluated the utilization of healthcare through telemedicine platforms to facilitate access to novel therapies such as voxelotor for patients with SCD. Methods 13 patients (≥18 years of age as of January 1, 2020) with SCD who had begun treatment with voxelotor between January 1, 2020 and December 31, 2020 were included in the initial analysis. Six patients were excluded from final analysis: three discontinued treatment due to side effects, one was noncompliant with treatment, and two were lost to follow-up. Acute care utilization, measured by the number of times each patient visited the ER, urgent care clinic, and hospital was compared for each patient in the period six months prior to their first dose of voxelotor and in the period six months after their last dose of the drug in 2020 using paired t-tests and Wilcoxon matched-pairs signed rank tests. Demographic information and the type of visit at which patients agreed to proceed with voxeletor was recorded for each patient. Simple linear regressions and multiple regressions controlled for covariates, defined as sex, BMI, age, type of insurance coverage, and duration of treatment. Results All seven (100%) patients discussed voxelotor treatment with their provider during a telehealth video visit. In the period before initiating treatment, patients frequented the ER an average of 2.71 (SD=6.75) times. In the six months after their last dose, patients visited the ER less than they had in the period prior to treatment, on average 0.57 (SD=0.79) times. This difference did not achieve statistical significance (p>0.9999). The mean number of visits to the urgent care clinic in the six months before treatment was 2.71 (SD=6.75) compared to 2 (SD=4) in the period after patients' last dose in 2020. This finding was not statistically significant (p>0.9999). Hospitalizations, on average, decreased significantly from 5.14 (SD=2.34) in the six months before starting treatment to 1.57 (SD=0.98) after ending therapy for 2020 (p=0.0015). Covariates did not have an effect on the differences in acute care utilization before treatment and after last treatment in 2020. Conclusions The findings of this study imply that treatment with voxelotor was associated with a decrease in the frequency of hospitalizations for the seven patients analyzed. This finding can potentially be attributed to the efficacy of voxelotor in improving anemia and reducing complications associated with SCD. While the difference between ER visits and urgent care visits before treatment and after the last dose in 2020 did not achieve statistical significance, likely due to small sample size, the data does suggest a reduction in both outcomes. In addition, the observation that all visits in which patient and provider discussed and initiated treatment were virtual support the use of telemedicine technology to improve access to multidisciplinary care and novel therapies for SCD patients. The impact of voxelotor treatment will continue to be assessed in SCD patients at our institution, and more data from clinical encounters will lead to a greater understanding of the efficacy of voxelotor. Figure 1 Figure 1. Disclosures Jain: GBT: Speakers Bureau; Novartis: Speakers Bureau; Sanofi: Other: advisory board; Argenx: Other: advisory board; DOVA: Other: advisory board.

Simulation-Based Training Program to Improve Cardiopulmonary Resuscitation and Teamwork Skills for the Urgent Care Clinic Staff

ABSTRACT Introduction Lack of high-quality cardiopulmonary resuscitation (CPR) and effective team communication during cardiovascular emergencies could lead to poor patient outcomes and adverse events. Studies have shown that CPR psychomotor skills declined 3 months and plateaued up to 6 months after the completion of CPR training. The Urgent Care Clinic (UCC) interprofessional staff did not receive consistent training on CPR and teamwork skills beyond what was received from the biannual American Red Cross (ARC) Basic Life Support (BLS) training and semiannual Resuscitative Care Function mock cardiac arrest. Most participants took their last CPR training for more than 6 months (n = 12, 67%), between 3 and 6 months (n = 2, 11%), and within the last 3 months before the pre-intervention period (n = 4, 22%). The purpose of the project was to form an interprofessional team to lead the development and implementation of a theory- and evidence-based simulation-based training program to improve CPR and teamwork skills while enhancing patient safety and emergency medical readiness in the hospital and UCC. Materials and Methods The quality improvement project utilized an interprofessional in situ simulation-based training to improve participants’ CPR and teamwork skills. The UCC physicians, nurses, and medical technicians completed a CPR and teamwork simulation-based training with a high-fidelity mannequin, pre-simulation preparation, briefing, and debriefing. The project collected pre-intervention and post-intervention data for CPR competence and teamwork perceptions. A paired t-test was used to assess differences in participant CPR skills and Team Strategies to Enhance Performance and Patient Safety Teamwork Perceptions Questionnaire responses before and after the simulation-based training intervention. The 59th Medical Wing and the University of South Alabama Institutional Review Boards approved the quality improvement project. Results A total of 18 participants completed the ARC BLS and Team Strategies to Enhance Performance and Patient Safety simulation-based training. Most participants were medical technicians (n = 8, 44%), followed by physicians (n = 5, 28%) and (n = 5, 28%) nurses. There was a statistical significance in participants’ ARC BLS scores, with a pre-simulation mean score of 45.42 and a post-simulation mean score of 89.21 (P = .000, 95% CI = 36.89-50.68). For Team Strategies to Enhance Performance and Patient Safety teamwork perceptions, there was a statistically significant increase in the participants’ teamwork perception levels, with a pre-simulation mean score of 4.61 and a post-simulation mean score of 4.86 (P = .000, 95% CI = 0.20-0.31). Conclusions Our results demonstrated that the participants’ ARC BLS scores and UCC’s team perceptions have increased after in situ simulation-based training. We did not assess the ideal time for re-training. We recommend a 3- to 6-month post-training assessment to determine the optimal time for a CPR and teamwork refresher training. A high-fidelity simulation-based program with trained facilitators that assess the healthcare providers’ CPR and teamwork skills could enhance the delivery of high-quality CPR and execution of effective teamwork skills in their workplace.

Urgent care in the community: an observational study

PurposeThis case study describes a community-based urgent care clinic in a general practitioner (GP) super clinic in South East Queensland.Design/methodology/approachThis retrospective chart audit describes patient demographic characteristics, types of presentations and management for Sundays in 2015.FindingsThe majority of patients (97%) did not require admission to hospital or office investigations (95%) and presented with one condition (94%). Of the presentations, 66.5% were represented by 30 conditions. Most patients received a prescription (57%), some were referred to the pathology laboratory (15%) and some were referred to radiology (12%). A majority (54%) of patients presented in the first three hours. Approximately half (51%) of patients presenting were aged under 25. More females (53%) presented than males. A majority (53%) lived in the same postcode as the clinic. The three most common office tests ordered were urinalysis, electrocardiogram (ECG) and urine pregnancy test. Some patients (19%) needed procedures, and only 3% were referred to hospital.Research limitations/implicationsThe study offers analysis of the client group that can be served by an urgent care clinic in a GP super clinic on a Sunday. The study provides an option for emergency department avoidance.Originality/valueDespite calls for more research into community-based urgent care clinics, little is known in Australia about what constitutes an urgent care clinic. The study proposes a classification system for walk-in presentations to an urgent care clinic, which is comparable to emergency department presentations.

Reactive arthritis: an unusual presentation of acute Clostridioides difficile colitis

A 20-year-old Caucasian man with a history of psoriasis presented to the emergency department due to a 2-week history of severe polyarthralgia and a 3-week history of non-bloody diarrhoea. The initial workup 2 days prior in an urgent care clinic returned negative for all enteric pathogens including Clostridioides difficile nucleic acid amplification test. Investigations revealed colitis on CT and pseudomembranous colitis on colonoscopy. The aspirate returned positive for C. difficile toxin. Tissue biopsies of the ascending, transverse, sigmoid colon and rectum were negative for chronicity to suggest inflammatory bowel disease with extraintestinal manifestation as the aetiology of polyarthralgia, which had been the most likely differential diagnosis until that point. The biopsy confirmed the diagnosis of reactive arthritis in the setting of C. difficile colitis. The patient improved on treatment with naproxen and was referred to rheumatology where he was found to be HLA-B27 positive.

Do Pruritus and Urticaria Predict For Response to Antihistamine Therapy in COVID-19 Patients with Pulmonary Symptoms?

Dear Editor, Skin manifestations and respiratory symptoms are commonly seen in patients with COVID-19. While infection by SARS-CoV-2 and an accompanying cytokine storm are proposed to account for respiratory symptoms, additional inflammatory mediators including histamine may also contribute. In this regard, we report the resolution of dyspnea associated with urticaria in a 61-year-old female patient acutely infected with SARS-CoV-2. The patient’s medical history is significant for idiopathic thrombocytopenic purpura, hypertension, and gastroesophageal reflux disease, and her long-standing medications consisted of eltrombopag, hydrochlorothiazide, lisinopril, and pantoprazole. The patient had no prior history of urticaria, angioedema, or respiratory illness. Due to the severity of her symptoms which developed over the course of a few days, the patient was referred to an urgent care clinic where intravenous methylprednisolone was administered, and tapering doses of prednisone were prescribed starting at 50mg. Nevertheless, all of her symptoms, particularly the urticaria (Figure 1 a,b), continued to worsen, prompting her to visit our dermatology clinic where she was started on hydroxyzine 25mg q.d. and topical triamcinolone acetonide 0.1%. A first-generation antihistamine was selected to address both pruritus and associated insomnia. Additionally, prednisone was discontinued as there was no response to the medication. The patient experienced relief of urticaria within 4 hours after starting hydroxyzine and reported improvement of her dyspnea by the following morning. A SARS-CoV-2 test performed at the urgent care clinic was positive for the detection of viral antigen. The patient’s symptoms completely resolved within 5 days after initiating hydroxyzine. The signs and symptoms of mast cell activation including urticaria and pruritus and response to antihistamines suggest that mast cells and their chemical mediators play a significant role in the pathophysiology of some COVID-19 patients. While case reports have described improvement of urticaria and other mast cell-mediated symptoms in COVID-19 patients following the administration of antihistamines, these cases were co-founded by the concomitant addition of new medications; this issue is less relevant in our report.1 Urticaria is a common dermatologic manifestation of COVID-19 patients, with an incidence of 19% in a prospective study of 375 patients.2 No correlation between urticaria and disease severity, or timing of onset has been described.3 Possible etiologies of urticaria in COVID-19 patients include a reaction to viral infection, medications, and stress. The SARS-CoV-2 virus itself may directly activate mast cells via toll-like receptors or signaling molecules such as interferon type 1, TNF-α, and/or chemokines.4 It is thought that mast cell degranulation may either be caused directly by the virus or indirectly through viral stimulation of complement fragments C3a and C5a activating G-protein-coupled receptors.4 While cytokine storms, and more recently, bradykinin storms, are proposed as mediators in the pathophysiology of COVID-19, mast cells and histamine may also contribute to the development of pulmonary manifestations of COVID-19 patients.5 The clinical course of our patient indicates her respiratory symptoms appeared solely related to SARS-CoV-2 induced urticaria. Release of histamine, prostaglandin-D2, and leukotriene-C4 by mast cells cause bronchoconstriction.6 Further, the release of mast cell cytokines such as IL-1 and IL-6 contribute to the development of pulmonary and systemic inflammation, as well as urticaria in COVID-19 patients.3,4,6,7 Preliminary clinical trial reports suggest antihistamine treatment mitigates pulmonary symptoms in COVID-19 patients. Trials of dual-histamine receptor blockade with cetirizine-famotidine in hospitalized COVID-19 patients with severe pulmonary symptoms resulted in marked reductions in rates of intubation, mortality, and length of hospital stay.8 Additionally, a retrospective study of 1,620 COVID-19 patients who received the H2 receptor antagonist famotidine, showed a statistically significant reduction in the rates of intubation and death.9 Based on the observations that urticaria and pruritus may accompany pulmonary symptoms, we postulate these patients may better respond to antihistamine therapy. Therefore, we suggest these dermatologic findings are incorporated into the analysis plans of clinical studies assessing antihistamines in COVID-19 patients with pulmonary symptoms. Further, we suggest considering antihistamines as a component of the first-line treatment for COVID-19 patients with urticaria.

Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type, a Convoluted Path to Diagnosis

Primary cutaneous diffuse large B cell lymphoma is a rare and aggressive form of primary cutaneous B-cell lymphoma. It typically presents with reddish to brown-nodules on the distal legs. We introduce the case of a 71 year-old female who presented to an urgent care clinic with a new onset of painful nodules on her right lower extremity. After workup and treatment for superficial thrombophlebitis, the patient improved until she presented to her primary care physician with worsening symptoms one month later. Diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type was confirmed via biopsy. After referral to oncology, further workup showed stage 4 disease. The patient was subsequently scheduled to begin treatment with R-CHOP. Unfortunately, prior to the initiation of chemotherapy she passed away after contracting COVID-19 pneumonia.

A comparison of disease burden and symptoms with age among CoVid-19 patients from data in a Florida clinic

Our knowledge of the disease burden and symptoms with age in COVID-19 patients is limited. Therefore, it is of interest to document the clinical aspect of this association with respect to the disease. We used the data of 3363 patients enrolled with an urgent care clinic in Volusia county, Florida for this study. Data shows difference in age among COVID-19 antibody (Ab) - positive patients (48.3 years, 95% CI = 46.9, 49.7 years) and Ab-negative patients (46.1 years, 95% CI = 45.4, 46.8 years). However, disease burden by age is not significant on average. Nonetheless, COVID-19 positive patients between 40-69-years of age experienced the highest burden of disease and highest average number of symptoms. Thus, COVID-19 disease burden and number of symptoms experienced were highest among the 40-69-year-old patients. Those above the populations mean age of 46.4 years old were more likely to test positive for COVID-19.