Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease.

Objective: To review the efficacy and safety of crizanlizumab (Adakveo) in the prevention of vaso-occlusive pain crises in sickle cell disease. Data Sources: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to January 2021) was completed using the terms crizanlizumab, SEG101, SelG1, and sickle cell disease. Manufacturer prescribing information, article bibliographies, and data from clinicaltrials.gov were incorporated in the reviewed data. Study Selection/Data Extraction: All studies registered on clinicaltrials.gov were incorporated in the reviewed data. Data Synthesis: Crizanlizumab is the first monoclonal antibody approved for sickle cell disease to reduce the frequency of vaso-occlusive crises. One phase 2 clinical trial and a post hoc analysis of the trial have been published. Relevance to Patient Care and Clinical Practice: Crizanlizumab is a monthly intravenous infusion approved by the Food and Drug Administration for patients with sickle cell disease 16 years of age and older to reduce the frequency of vaso-occlusive crises. Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns include drug cost and administration. Long-term benefits and risks have not been determined.

Intentional ingestion of hand sanitizer in an adult psychiatric unit.

Intentional ingestion of ethanol- or isopropanol-based hand sanitizer has been reported in the literature in a variety of settings within the health care system. Specifically in psychiatric units, case reports have only described ingestion of ethanol-based products. This report describes a case of intentional ingestion of isopropanol-based hand sanitizer by a patient while hospitalized on a psychiatric unit. The patient developed acute respiratory failure, acute kidney injury, and metabolic encephalopathy and was treated for 3 days in the intensive care unit before returning to the psychiatric unit. This case highlights the process of identifying suspected ingestion while hospitalized. In any patient who has a sudden change in level of consciousness, clinicians should consider the potential for ingestion of ethanol- or isopropanol-based hand sanitizer. Facilities should be aware of how accessible hand sanitizer is, particularly in areas with patients who have a history of substance dependence.

Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy.

OBJECTIVE: To review the efficacy and safety of onasemnogene abeparvovec-xioi (Zolgensma) in the treatment of spinal muscular atrophy (SMA). DATA SOURCES: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to December 2019) was completed using the terms onasemnogene, AVXS-101, and spinal muscular atrophy. Manufacturer prescribing information, article bibliographies, and data from ClinicalTrials.gov were incorporated in the reviewed data. STUDY SELECTION/DATA EXTRACTION: All studies registered on ClinicalTrials.gov were incorporated in the reviewed data. DATA SYNTHESIS: Onasemnogene is the first agent for SMA utilizing gene therapy to directly provide survival motor neuron 1 (SMN1) gene to produce SMN protein. Four publications of 1 clinical trial, 1 comparison study of treatment effects, and 1 combination therapy case series have been published. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Onasemnogene is a one time dose approved by the Food and Drug Administration for SMA patients <2 years old who possess mutations in both copies of the SMN1 gene. CONCLUSION: Onasemnogene appears to be an efficacious therapy for younger pediatric patients with SMA type 1. Concerns include drug cost and potential liver toxicity. Long-term benefits and risks have not been determined.

Nusinersen: A Treatment for Spinal Muscular Atrophy.

OBJECTIVE: To review the efficacy and safety of nusinersen (Spinraza) in the treatment of spinal muscular atrophy (SMA). DATA SOURCES: An English-language literature search of PubMed and MEDLINE (1946 to June 2018) was performed using the terms nusinersen, ISIS-SMN (Rx), and spinal muscular atrophy. Manufacturer prescribing information, abstracts, article bibliographies, and clinicaltrials.gov data were incorporated for additional materials. STUDY SELECTION/DATA EXTRACTION: All clinical trials of nusinersen were identified and analyzed in the review. DATA SYNTHESIS: Nusinersen is the first drug therapy approved for the treatment of SMA. It is a novel modified antisense oligonucleotide designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron protein deficiency. Nusinersen has been studied for safety, pharmacokinetics, and efficacy in both open-label and randomized controlled trials. The studies show improvement in motor function across SMA of all types. The most common adverse effects were respiratory tract infections, headache, back pain, constipation, and post-lumbar puncture syndrome. Relevance to Patient Care and Clinical Practice: Based on phase III trial data, nusinersen produced positive changes in the clinical course of patients with SMA. The acquisition and administration of nusinersen present a number of challenges in clinical practice. Its intrathecal delivery and costly price tag must be recognized. CONCLUSION: Nusinersen is safe and effective in patients with SMA. It was well tolerated across all studied age groups.

Duloxetine-associated tachycardia.

OBJECTIVE: To report a case of symptomatic tachycardia that was successfully treated with propranolol in a patient receiving duloxetine. CASE SUMMARY: A 26-year-old man presented with episodes of fatigue, tachycardia, diaphoresis, and chest pain approximately 2 months after the initiation of duloxetine 20 mg/day for dysthymic disorder. Cardiac workup including echocardiogram, exercise treadmill testing, and Holter monitoring was negative, except for tachycardia (heart rate 110-120 beats/min). Duloxetine was withheld, and the patient's heart rate returned to normal in less than a week. Duloxetine was restarted at the same dosage, and tachycardia returned within 2 days. Propranolol was added to the treatment regimen to lower the heart rate. Because of therapeutic failure of other antidepressants, duloxetine was continued because of its beneficial effects on mood. DISCUSSION: One published case report describing tachycardia in association with duloxetine in 2 heart failure patients was found in a MEDLINE search (1966-July 2008). Increased blood pressure and heart rate have been reported in duloxetine trials. The proposed mechanism for duloxetine-induced tachycardia is its effects on norepinephrine, which impact the cardiovascular system. Use of the Naranjo probability scale indicated duloxetine as a probable cause of this patient's tachycardia. CONCLUSIONS: Clinicians should be aware of the possibility of clinically significant tachycardia in patients receiving duloxetine, even in low doses.

Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome.

OBJECTIVE: To review the published reports of neuroleptic malignant syndrome (NMS) associated with the use of selective serotonin-reuptake inhibitors (SSRIs) and second-generation antipsychotics. DATA SOURCE: Information was selected from a MEDLINE search of English-language literature (1950-May 2008). Manual search of all published cases indexed in MEDLINE (English language only) of NMS associated with second-generation antipsychotics was also performed. STUDY SELECTION AND DATA EXTRACTION: Pertinent information from all reports obtained was included, with specific emphasis on patient age, sex, second-generation antipsychotic involved, SSRI or other antidepressant involved, time of onset of NMS symptoms in relation to medication changes, treatment administered, and outcome of the reaction. DATA SYNTHESIS: NMS has been reported with every second-generation antipsychotic agent. It is unclear whether concomitant therapy with other agents may increase the risk of NMS development via pharmacodynamic or pharmacokinetic mechanisms or both. The suggested pharmacodynamic mechanism for increased risk of NMS with concomitant use of SSRIs is the effect of serotonin on dopamine release. Serotonin further inhibits dopamine release and thereby may worsen a hypodopaminergic state induced by antipsychotics. Pharmacokinetic factors may also play a role in some NMS cases involving an SSRI by increasing antipsychotic concentrations. An examination of case reports seems to indicate that at least in some cases, a temporal relationship exists with the addition of an SSRI to existing antipsychotic therapy. CONCLUSIONS: The use of SSRIs may be associated with an increased risk of NMS development in those receiving second-generation antipsychotics. Clinicians should closely monitor patients for the potential development of NMS.

Olanzapine-associated neuroleptic malignant syndrome in a patient receiving concomitant rivastigmine therapy.

Neuroleptic malignant syndrome (NMS) is an idiosyncratic and uncommon but serious adverse effect that has been reported with both typical and atypical antipsychotic agents. We describe a 58-year-old man with Down syndrome and dementia who was receiving low-dose olanzapine and rivastigmine therapy; he developed NMS 4 months after starting olanzapine. The patient presented with altered mental status, rigidity, fever, diaphoresis, and tremor, and his creatine kinase level was elevated. Olanzapine was discontinued, and the patient fully recovered; antipsychotic therapy was not restarted. Based on the Naranjo adverse drug reaction probability scale, olanzapine was the probable cause of the patient's NMS. In addition, use of rivastigmine in combination with olanzapine may have placed the patient at greater risk for NMS, possibly due to an acetylcholine-dopamine imbalance. Clinicians should be aware of the potential for NMS even with low doses of antipsychotics, particularly in patients who have a limited ability to communicate. Concomitant administration of cholinesterase inhibitors such as rivastigmine may represent an unrecognized risk factor for NMS development.

A case report of neonatal thyrotoxicosis due to maternal autoimmune hyperthyroidism.

A case of neonatal thyrotoxicosis secondary to maternal autoimmune hyperthyroidism is reported in an infant born at 34 weeks gestation who presented with tachycardia, jitteriness, diarrhea, and a small goiter. Propranolol and oxygen were used to treat high-output cardiac failure and transient persistent pulmonary hypertension. The infant's response to propylthiouracil therapy, gradual resolution of cardiac and systemic symptoms, and normaliziation of thyroid studies are described. Thyroid physiology and function and the special considerations in a premature infant are reviewed. An overview of maternal autoimmune hyperthyroidism and the implications for the developing fetus and neonate are presented. The risk factors for, and clinical presentation of, hyperthyroidism are outlined and treatment strategies highlighted. The nursing care of infants with hyperthyroidism is carefully described with an emphasis on the surveillance for and management of multisystem manifestations.