Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date.

Sickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin ß-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.

Review of Medication Therapy for the Prevention of Sickle Cell Crisis.

This article reviews the clinical data concerning the uses of hydroxyurea, L-glutamine, and crizanlizumab in treating pain crises associated with sickle cell disease.

Evaluation of Bleeding Events Requiring Hospitalization in Patients With Atrial Fibrillation Receiving Dabigatran, Warfarin, or Antiplatelet Therapy.

OBJECTIVE: To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel). METHODS: This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy. RESULTS: Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04). CONCLUSION: Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Breaking the Mold: A Review of Mucormycosis and Current Pharmacological Treatment Options.

OBJECTIVE: To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. DATA SOURCES: An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. STUDY SELECTION AND DATA EXTRACTION: Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. DATA SYNTHESIS: Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. CONCLUSION: Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B.

Frequency and characteristics of hospital-sponsored pertussis revaccination programs in the southern United States.

OBJECTIVE: The Centers for Disease Control and Prevention (CDC) released guidelines in December, 2006, recommending revaccination against Bordetella pertussis with Tdap for all post-partum women and healthcare workers. The CDC recommendations specifically state "the postpartum Tdap should be administered before discharge from the hospital or birthing center" and "hospitals and ambulatory-care facilities should provide Tdap for healthcare personnel." The purpose of this survey was to determine the frequency and characteristics of hospital-sponsored pertussis revaccination programs in the southern United States. METHODS: A twenty-six question electronic survey was sent to a representative of either the infection control or pharmacy department of hospitals in the following south central states: Kentucky, Tennessee, Alabama, Mississippi, Arkansas, Louisiana, Oklahoma, and Texas. The survey was designed to collect information regarding the institution's demographic factors and Tdap vaccination policies. RESULTS: Thirty-seven of 120 surveys (30.8%) were returned. Thirty respondents (81.1%) reported awareness of the 2006 CDC recommendations. Of the 29 institutions offering labor and delivery services, 14 (48.3%) confirmed having a post-partum vaccination policy, 12 (41.4%) reported having no post-partum vaccination policy, and 3 (10.3%) were unaware of whether a policy was currently in place. Of the 37 responding institutions, 34 (91.9%) offer employee vaccinations, although only 31 of those 34 programs (91.1%) offer Tdap to employees. CONCLUSION: According to survey responses, many institutions have not yet implemented Tdap vaccination programs for post-partum patients or healthcare workers according to CDC recommendations. There was no correlation between institution demographics and the presence or characteristics of Tdap revaccination programs.