Case Report: Delayed Alemtuzumab-Induced Concurrent Neutropenia and Thrombocytopenia in Relapsing-Remitting Multiple Sclerosis.

Alemtuzumab is an anti-CD52 monoclonal antibody used to treat relapsing-remitting multiple sclerosis following failure of second-line medications. It is administered intravenously in 2 treatment sequences 1 year apart. This drug is frequently associated with mild infusion reactions within days of administration, increased infection risk, and long term adverse events from secondary autoimmunity. Alemtuzumab-induced serious immune-mediated thrombocytopenia (ITP) is well-reported and occurred in 1.0-2.2% of participants in initial phase 2 and 3 trials for multiple sclerosis. Significant neutropenia, however, is rare and was only observed in 0.1% of study participants. Delayed neutropenia and/or ITP is thought to occur from secondary autoimmunity. Few case reports have described severe neutropenia occurring beyond 2 months of last alemtuzumab dose. We present an unusual case of delayed combined neutropenia and thrombocytopenia that occurred 15 months after the second infusion of alemtuzumab. The patient was asymptomatic and presented following discovery of neutropenia and thrombocytopenia during routine laboratory studies. The patient responded to steroids initially and was discharged, although outpatient cell counts subsequently revealed recurrent neutropenia and ITP. The adverse drug reaction probability (Naranjo) scale was completed and showed probable likelihood that the adverse event was alemtuzumab-related. Long term screening for delayed hematologic abnormalities, at least 4 years after initial dose, is necessary when using alemtuzumab. Greater research is needed to understand the mechanism of drug-associated neutropenia.

Driving Impairment and Healthcare Provider Counseling in Rheumatoid Arthritis and Osteoarthritis Patients: A Cross-Sectional Survey.

BACKGROUND/OBJECTIVE: To examine rates of counseling on driving for individuals with osteoarthritis (OA) and/or rheumatoid arthritis (RA) and evaluate the Health Assessment Questionnaire Disability Index (HAQ-DI) as a screening tool for further driving evaluation. METHODS: A cross-sectional survey was completed by individuals recruited via ResearchMatch (a national web-based recruitment tool) between March 5 and April 20, 2020. Individuals with a current US driver's license, ≥18 years old, with self-reported OA and/or RA diagnosis were surveyed about driving difficulty and vehicle modification and completed a HAQ-DI assessment. Respondents were dichotomized based on reporting vehicle modification(s) due to arthritis versus no modification(s) for univariate and multivariate analyses. RESULTS: Of 4,435 recruited patients, 304 (6.9%) met inclusion/exclusion criteria and completed the surveys. Of all respondents, 259 (85.2%) reported at least some difficulty with one or more driving activities, but only 47 (15.5%) reported discussion with a physician and/or healthcare professional. A total of 184 (60.5%) respondents had HAQ-DI ≥ 1 and were more likely to report vehicle modification(s) compared to respondents with HAQ-DI score < 1 (OR = 5.00, 95% CI = 2.69-9.32, p < 0.011) after controlling for age, gender, type of arthritis, and driving behaviors. CONCLUSION: Few respondents report discussion of driving difficulties with healthcare providers, although many report driving-related impairments, particularly those with HAQ-DI scores ≥ 1. Our data suggest a strong association between HAQ-DI scores and vehicle modification. The HAQ-DI may serve as a screening tool to predict a patient's need for driving evaluation and vehicle modification(s).

Outcomes of Continuous Renal Replacement Therapy in a Community Health System.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is commonly used in critically ill, hemodynamically unstable patients with acute kidney injury (AKI). This procedure is resource intensive with reported high in-hospital mortality. We evaluated mortality with CRRT in our healthcare system and markers associated with decreased survival. METHODS: A retrospective cohort study collected data on patients 18 years or older, without prior history of end stage kidney disease (ESKD), who received CRRT in the intensive care units at one of three hospitals in our health system in Columbus, OH from July 1, 2016 to July 1, 2019. Data included demographics, presenting diagnosis, comorbidities, laboratory markers, and patient disposition. In-hospital mortality rates and sequential organ failure assessment (SOFA) scores were calculated. We then compared information between two groups (patients who died during hospitalization and survivors) using univariate comparisons and multivariate logistic regression models. RESULTS: In-hospital mortality was 56.8% (95%CI: 53.4-60.1) among patients who received CRRT. Mean SOFA scores did not differ between survival and mortality groups. The odds for in-patient mortality were increased for patients age ≥60 (OR = 1.74, 95%CI: 1.23-2.44), first bilirubin >2 mg/dL (OR = 1.73, 95%CI: 1.12-2.69), first creatinine < 2 mg/dL (OR = 1.57, 95%CI: 1.04-2.37), first lactate > 2 mmol/L (OR = 2.08, 95%CI: 1.43-3.04). The odds for in-patient mortality were decreased for patients with cardiogenic shock (OR = .32, 95%CI: .17-.58) and hemorrhagic shock (OR = .29, 95%CI: .13-.63). CONCLUSIONS: We report in-hospital mortality rates of 56.8% with CRRT. Unlike prior studies, higher mean SOFA scores were not predictive of higher in-hospital mortality in patients utilizing CRRT.

Warm Autoimmune Hemolytic Anemia Associated With Asymptomatic SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant coronavirus disease 2019 (COVID-19) are associated with several hematologic abnormalities, including immune thrombocytopenia, antiphospholipid syndrome, and autoimmune hemolytic anemia (AIHA). Initial case reports suggested immune dysregulation to be the underlying etiology of SARS-CoV-2-associated AIHA, as all reported cases involved patients with moderate to severe COVID-19, many of whom had underlying lymphoproliferative disorders. More recently, AIHA has been reported in patients with mildly symptomatic SARS-CoV-2 infection. Here, we detail a patient with asymptomatic SARS-CoV-2 infection who presented with severe, symptomatic anemia. Workup was consistent with warm autoimmune hemolytic anemia (WAIHA) secondary to SARS-CoV-2 infection.

Acute Effusive Pericarditis: A Late Complication of COVID-19.

As the COVID-19 pandemic evolves, the medical community continues to discover novel clinical manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Often, extrapulmonary manifestations occur simultaneously with pulmonary disease. However, there is a paucity of literature describing the cardiac manifestations of COVID-19 in the absence of pulmonary findings. We report a rare case of acute pericarditis presenting with pericardial effusion and cardiac tamponade in a 43-year-old man diagnosed with COVID-19. This case emphasizes the importance of continued investigation regarding diagnosis and treatment of COVID-19 and its related symptoms.

Structure-guided discovery of a novel, potent, and orally bioavailable 3,5-dimethylisoxazole aryl-benzimidazole BET bromodomain inhibitor.

The bromodomain and extra-terminal (BET) family of proteins, consisting of the bromodomains containing protein 2 (BRD2), BRD3, BRD4, and the testis-specific BRDT, are key epigenetic regulators of gene transcription and has emerged as an attractive target for anticancer therapy. Herein, we describe the discovery of a novel potent BET bromodomain inhibitor, using a systematic structure-based approach focused on improving potency, metabolic stability, and permeability. The optimized dimethylisoxazole aryl-benzimidazole inhibitor exhibited high potency towards BRD4 and related BET proteins in biochemical and cell-based assays and inhibited tumor growth in two proof-of-concept preclinical animal models.

Multidisciplinary Approach to Improve Sepsis Outcomes.

Severe sepsis and septic shock cause significant morbidity and mortality with health care costs approximating $17 billion annually. The Surviving Sepsis Campaign 2012 recommended time-sensitive care bundles to improve outcomes for patients with sepsis. At our community teaching hospital, a review of sepsis management for patients admitted to a medical intensive care unit (ICU) between December 2015 and March 2016 found 70.8% compliance with timing of lactate draw, 65.3% compliance for blood cultures, and 51.4% compliance with antibiotic administration recommendations. Thus, a quality improvement initiative to improve detection and time to bundle completion for ICU-level patients was designed. Previous studies suggest that utilization of sepsis alert systems and sepsis response teams in the emergency department setting is associated with improved compliance with recommended sepsis bundles and improved hospital mortality. Therefore, a "sepsis alert" protocol was implemented that used both an electronic alert and an overhead team alert that mobilized nursing, pharmacy, phlebotomy, and a senior internal medicine resident to bedside. In addition, a template to document sepsis diagnosis and bundle adherence was created. After implementation, we noted improvement in appropriately timed serum lactate, 88.6% versus 70.8% (p = .008) with no significant improvements in blood cultures, antibiotic administration, or mortality.

Tumour lysis syndrome: a rare side effect of imatinib therapy for GIST.

Tumour lysis syndrome (TLS) is a life-threatening complication wherein massive tumour cell lysis results in severe metabolic abnormalities. TLS generally follows chemotherapy of rapidly proliferating haematological malignancies; spontaneous TLS and TLS from treatment of solid tumours are infrequently reported. We present a rare case of TLS following treatment of a large gastrointestinal stromal tumour (GIST) in a 63- year-old man. Imatinib was started for tumour size reduction prior to surgical intervention and in 5 days the patient developed metabolic derangements consistent with TLS. Imatinib was held and fluids, allopurinol and rasburicase were started. All metabolic abnormalities resolved in 3 days. Imatinib was restarted, and he eventually underwent surgical intervention. This is the second case demonstrating successful reinitiation of imatinib following TLS when treating GIST. We highlight the importance of risk factor assessment and need for pre-emptive therapy to prevent TLS when using tyrosine kinase inhibitor therapy.

The Effect of an Educational Pamphlet on Patient Knowledge of and Intention to Discuss Screening for Obstructive Sleep Apnea in the Acute Ischemic Stroke Population.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and stroke is well established, thus supporting the importance of secondary prevention via screening and treatment for acute ischemic stroke survivors. Educational pamphlets are commonly used for patient education; however, none currently available on OSA have evaluated. The aim of this study was to evaluate the effect of a brief educational intervention on patient knowledge and interest in OSA screening. METHODS: Adult acute ischemic stroke patients were enrolled into a nonrandomized, single-group, pretest and posttest study. Inclusion criteria included minor or moderate stroke per the National Institutes of Health Stroke Scale score of 1 to 15, with a level of consciousness score of 0. Patients with known dementia or OSA were excluded. After the preintervention survey, patients were given an educational pamphlet reviewing OSA and stroke. A postintervention survey was administered 24 to 72 hours later. Outcomes included an 8-question knowledge test standardized to percentiles, intention to speak with a physician about screening on a 7-point scale (1, not at all likely, to 7, very likely), and perception of the pamphlet's educational value on a 7-point scale (1, not valuable, to 7, quite valuable). RESULTS: Of 124 eligible patients, 36 consented and 26 completed both preintervention and postintervention surveys. Preintervention knowledge scores averaged 69.7% (SD, 21.3%), postintervention scores averaged 80.8% (SD, 21.0%), P = .005, with an effect size of 1.00. Likelihood of speaking with a physician about OSA testing improved from 3.5 (SD, 2.0) to 5.0 (SD, 1.8), P = .001, with an effect size of 0.89. Pamphlet educational value was scored at 5.2 (SD, 1.7). CONCLUSIONS: A brief educational pamphlet written using health literacy concepts was considered valuable and improved patient knowledge and intention to discuss OSA screening with a physician. Further work is needed to determine whether the pamphlet can promote a discussion and referral for OSA screening at the primary care level.

Impact of a telemedicine eICU cart on sepsis management in a community hospital emergency department.

Introduction Intensivist involvement for patients with sepsis is associated with decreased complications and mortality, and lower hospital resource utilization, but few studies have evaluated outcomes for patients exposed to electronic intensive care unit (eICU) telemedicine sepsis management in the emergency department (ED). In this study, we assess whether eICU cart exposure in the ED improved compliance with components of the 2010 Surviving Sepsis Campaign bundles, length of stay (LOS), disposition and hospital costs. Methods An institutional review board-approved, retrospective cohort study was completed on patients with confirmed sepsis who presented to our ED from July 2010 through February 2013. Results Of 711 patient ED encounters, 314 cases met criteria for analysis (95 exposed and 219 non-exposed). Patient cohorts had similar demographics and comorbid International Classification of Diseases, Ninth Edition (ICD-9) diagnoses. The exposed cohort received antibiotics more quickly (122.3 minutes ±83.3 versus 163.4 minutes ±204.4, p = 0.043) and were more likely to have lactic acid levels drawn within six hours (98.9% vs. 90%, p = 0.019). The exposed cohort had a shortened ED LOS (in days) 0.08 ± 0.28 versus 0.16 ± 0.37, p = 0.036. Hospital LOS, disposition and death were similar in both cohorts. Total hospital costs for the exposed cohort were lower and less variable (US$19,713 ± 16,550 vs. US$24,364 ± 25068), but this was not significant ( p = 0.274). Discussion Our findings suggest that in individuals with confirmed sepsis, ED exposure to a telemedicine-based eICU cart impacted adherence to aspects of the Surviving Sepsis Campaign recommended bundle, but did not impact overall survival and medical costs.

Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient.

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy, immunocompetent 37-year-old woman. She initially presented to an urgent care centre with a classic HZ rash localised to her neck, and upper respiratory symptoms and was treated with prednisone and cephalexin. Within 1 week, the rash became diffuse and her clinical status rapidly deteriorated with development of severe acute respiratory distress syndrome. Varicella zoster infection was confirmed via skin biopsy, bronchial viral PCR and serology for varicella antibodies. She was successfully treated with intravenous acyclovir and aggressive supportive care. Though physicians readily recognise typical zoster infection, this case reminds clinicians that HZ infection can be fulminant and potentially life-threatening in younger, immunocompetent individuals. Early recognition and antiviral therapy is important to reduce morbidity and mortality.

Hospitalist Versus Subspecialist Perspectives on Reasons, Timing, and Impact of Consultation.

BACKGROUND: Hospitalists frequently consult medical subspecialists in the management of inpatients. Given the potential impact on health resource utilization, it is important to understand the working relationship between these groups. METHODS: A cross-sectional survey of hospitalists, n = 655, and subspecialists across Ohio (nephrologists and endocrinologists), n = 293, was conducted to investigate perceptions and communication about reasons, timing, and impact of hospital consultations. RESULTS: Survey response rate was 13.3%. Hospitalists were more likely to report subspecialty request to serve as admitting physician with subsequent consultation 63.2% versus 26.7%, p < .001. Hospitalists with a daily workload ≥15 patients per day were more likely to report that this impeded their ability to manage details of patient care versus hospitalists with <15 patients per day, 53.2% versus 24.1%, p = .02, and resulted in subspecialty consultation for problems manageable by the hospitalist, 38.3% versus 6.9%, p = .003. Hospitalists were less likely than subspecialists to report major impact from consultation 50.0% versus 81.0%, p = .001 and they were more likely to report direct communication for urgent consults 97.3% versus 48.8%, p < .001. CONCLUSIONS: Future work should be aimed at addressing hospitalist workload, improving communication, and ensuring appropriate need and timing of consultation.

Associations with resident physicians' early adoption of electronic cigarettes for smoking cessation.

BACKGROUND: Use of the electronic cigarette for nicotine delivery has increased dramatically in recent years. Information continues to emerge on its role as a smoking cessation aid, but little is known about resident physician use of the device in clinical practice. METHODS: In 2015, an electronic survey was administered to resident physicians in one healthcare system in Columbus, Ohio. The survey included questions about personal smoking exposure, knowledge, beliefs, attitudes about electronic cigarettes and early adoption of electronic cigarettes with patients. Data were dichotomised based on a 'stages of change' model that assessed resident physician adoption of electronic cigarettes for therapeutic use. Data were analysed through χ2 tests and logistic regression using ORs and 95% CIs. RESULTS: Of 338 residents, 142 (42%) responded. Of all residents, 25 (17.7%) reported that they have been recommending electronic cigarettes to their patients for the past 6 months or longer. In the multivariate model, residents ≥postgraduate year (PGY)-3 (OR=3.68, 95% CI 1.20 to 11.29), peer-reviewed article exposure (OR=6.65, 95% CI 1.56 to 28.38) and the view that addictive potential is definitely or somewhat less than traditional cigarettes (OR=5.05, 95% CI 1.48 to 17.24) were associated with recommendation of electronic cigarettes. CONCLUSIONS: Few residents report recommending electronic cigarettes to patients who smoke. These residents consider the electronic cigarette less addicting than traditional cigarettes, supporting harm reduction strategies over strict abstinence. Most residents require further evidence-based education on efficacy and long-term safety of electronic cigarettes before recommending to their patients.

Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

New use for an old drug: oral ketamine for treatment-resistant depression.

Treatment-resistant depression (TRD) is a disabling disorder that can interfere with a patient's capacity to understand and participate in medical care and thus negatively impact individual morbidity and mortality. Hospitalised patients with TRD may require rapid alleviation of severe symptomatology, particularly when suicidal or if unable to participate in care decisions. Ketamine is well known for its anaesthetic effects and its use as a 'street' drug; however, its action as an N-methyl-D-aspartate receptor antagonist makes ketamine a potential therapy for TRD. The majority of studies investigating ketamine for TRD have used intravenous drug delivery, demonstrating benefit for rapid alleviation and sustained response of depression symptoms. Oral ketamine for urgent alleviation of TRD symptoms is less reported. We describe rapid alleviation of severe TRD with oral ketamine in a severely ill postoperative hospitalised patient, and review the current literature on 'off-label' use of ketamine for treatment of refractory depression.

Common variable immunodeficiency, immune thrombocytopenia, rituximab and splenectomy: important considerations.

Common variable immunodeficiency (CVID) is readily considered in patients presenting with recurrent sino-pulmonary infections, however this disease has a broad range of clinical manifestations and diagnosis can be delayed by several years. We present the case of a 44-year-old postpartum female who presented with nausea, vomiting and abdominal distension. Four years prior, she was hospitalized for treatment of immune thrombocytopenia (ITP) with splenectomy and rituximab followed by two episodes of bacterial meningitis despite immunizations. The recurrent meningitis had been attributed to splenectomy and immunotherapy. During this hospitalization, extensive workup for gastrointestinal pathology was negative and she was diagnosed with intestinal pseudo-obstruction. Her hospital course was complicated by development of severe pseudomonas pneumonia, and subsequent immunoglobulin testing and impaired antibody response to vaccines were consistent with CVID. We review the clinical presentation of CVID, its association with autoimmune disease, and treatment implications, specifically the impact of rituximab therapy and splenectomy on immunoglobulin function and risk of serious infection. Intestinal pseudo-obstruction has been reported in children with CVID, but literature search failed to reveal similar presentation in adults. Physicians must consider the heterogeneous clinical manifestations of CVID to avoid delay in diagnosis and treatment. Institution of appropriate therapy with immunoglobulin replacement is important to decrease risk of serious infection.

Associations with resuscitation choice: Do not resuscitate, full code or undecided.

OBJECTIVE: To examine associations of individual exposure and knowledge of resuscitation mechanics and prognosis with specific decision: Do Not Resuscitate (DNR), Full Code (FC) or Undecided (UD). METHODS: Cross-sectional questionnaire at 3 sites: geriatric assessment center, internal medicine resident clinic, and inpatient palliative care service. RESULTS: 407 completed the questionnaire: 27% identified as DNR, 24% as FC and 49% as UD. Few (11.8%) respondents reported discussion of DNR status with their primary care doctor. DNR choice was associated with knowledge of DNR mechanics, OR=2.30 (95%CI: 1.23-4.30), physician discussion, OR=5.58 (95%CI: 2.39-13.04) and confidence in understanding own health problems, OR=2.89 (95%CI: 1.04-8.04). FC choice was associated with knowledge of FC mechanics, OR=2.01 (95%CI: 1.03-3.93) and media code exposure, OR=3.80 (95%CI: 1.46-9.92). Knowledge of resuscitation prognosis was negatively associated with FC, OR =0.48 (95%CI: 0.23-0.98). CONCLUSION: Many individuals lack knowledge or understanding of resuscitation procedure, its risks, and prognosis. Educational efforts, for both patients and healthcare professionals, are needed to improve individual knowledge needed for informed decision. PRACTICE IMPLICATIONS: Scheduled time for physician-patient discussion remains important for education about individual health conditions and risk/benefits related to resuscitation.

Endofibrosis: an unusual cause of leg pain in an athlete.

Endofibrosis of the external iliac artery can occur as a rare complication of high endurance physical activities, particularly cycling, running, and rowing. Symptoms mimic claudication and typically occur with vigorous exercise and improve with rest. Patients can experience thigh pain, swelling and paresthesias in the affected extremity. The diagnosis of endofibrosis is often delayed given the patient's overall normal appearance and lack of significant medical history. This report outlines the presentation and evaluation of a case of endofibrosis of the external iliac artery in an otherwise healthy 42-year-old healthy woman. Her diagnosis was delayed for two years before appropriate diagnostic testing and subsequent surgical intervention allowed for return to a normal, active lifestyle.

Understanding the associations between modifying factors, individual health beliefs, and hemodialysis patients' adherence to a low-phosphorus diet.

OBJECTIVE: Hyperphosphatemia in end-stage renal disease is associated with significant morbidity and mortality. Because phosphorus is not effectively dialyzed, dietary adherence remains a significant problem. Previous studies have examined the health belief model, but none have looked at stages of change and dietary adherence in patients undergoing hemodialysis (HD). DESIGN: Cross-sectional survey. SETTING: Three dialysis centers in Columbus, Ohio, between August 2012 and March 2013. SUBJECTS: English-speaking patients age 18 or older on HD without dementia or developmental delay. INTERVENTION: None. MAIN OUTCOME MEASURE: Associations between dietary adherence based on the Precaution Adoption Process Model (stages of change) and serum phosphorus levels via a conceptual model incorporating modifying factors and individual health beliefs. RESULTS: Ninety-five patients completed the survey; 59 (62%) endorsed adherence to a low-phosphorus diet and 32 (34%) had phosphorus values ≤5.5 mg/dL. Modifying factors associated with diet adherence included nonminority status odds ratio (OR), 95%CI 8.99 (1.08-74.60), greater level of education OR 18.23 (1.62-205.00), better quality of life OR 9.28 (1.35-63.71), and time on dialysis OR 1.04 (1.01-1.07). Individual health beliefs associated with diet adherence included perceived benefits OR 3.18 (1.47-6.88) and self-efficacy OR 1.22 (1.09-1.38). Modifying factors associated with phosphorus control included: age OR 0.94 (0.90-0.99), minority status OR 0.11 (0.02-0.68), greater level of education OR 6.60 (1.41-31.04), knowledge about chronic kidney disease OR 1.48 (1.03-2.13), and time on dialysis OR 0.98 (0.96-0.99). Individual health beliefs associated with phosphorus control included self-efficacy OR 1.08 (1.01-1.16). CONCLUSION: HD clinicians and educators may obtain better results with dietary adherence and phosphorus control if they focus not only toward disease and dietary education but also on understanding modifying factors and individual health beliefs. Assessing where the patient is with regard to stages of change may assist health care providers in better matching interventions that build patients' self-efficacy.