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Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
The American Journal of Emergency... Aug 2023Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal... (Review)
Review
PURPOSE
Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods.
SUMMARY
There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use.
AREAS FOR FUTURE RESEARCH
The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.
Topics: Humans; Succinylcholine; Etomidate; Rocuronium; Rapid Sequence Induction and Intubation; Ketamine; Retrospective Studies; Hypnotics and Sedatives; Emergency Service, Hospital; Neuromuscular Blocking Agents; Intubation, Intratracheal
PubMed: 37196592
DOI: 10.1016/j.ajem.2023.05.004 -
JAMA Ophthalmology Oct 2023The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for...
IMPORTANCE
The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression.
OBJECTIVE
To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression.
DESIGN, SETTING, AND PARTICIPANTS
This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with -0.50 diopter (D) to -6.00 D spherical equivalent refractive error (SER) and no worse than -1.50 D astigmatism.
INTERVENTIONS
Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months.
MAIN OUTCOMES AND MEASURES
The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported.
RESULTS
A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, -0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, -0.08 mm; 95% CI, -0.13 mm to -0.02 mm; P = .005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, -0.13 mm; 95% CI, -0.19 mm to -0.07 mm; P < .001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03350620.
PubMed: 37261839
DOI: 10.1001/jamaophthalmol.2023.2097 -
JAMA Ophthalmology Aug 2023Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia.
IMPORTANCE
Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia.
OBJECTIVE
To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children.
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]).
INTERVENTION
Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation.
MAIN OUTCOME AND MEASURES
Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo.
RESULTS
A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95% CI, -0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, -0.115 to 0.134 mm).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03334253.
Topics: Child; Humans; Female; Child, Preschool; Atropine; Ophthalmic Solutions; Refraction, Ocular; Myopia; Vision Tests; Disease Progression
PubMed: 37440213
DOI: 10.1001/jamaophthalmol.2023.2855 -
Expert Opinion on Biological Therapy 2023The development of antibody-drug conjugates (ADCs) have revolutionized treatment for breast cancer. Sacituzumab govitecan (SG), a Trop2-targeted ADC, has demonstrated... (Review)
Review
INTRODUCTION
The development of antibody-drug conjugates (ADCs) have revolutionized treatment for breast cancer. Sacituzumab govitecan (SG), a Trop2-targeted ADC, has demonstrated remarkable efficacy in triple-negative breast cancer (TNBC) and hormone receptor-positive metastatic breast cancer.
AREAS COVERED
We summarize the evidence for SG use in the treatment of metastatic breast cancer, discuss the toxicity profile, and present strategies to manage adverse events.
EXPERT OPINION
Hematologic toxicities are frequently observed with SG therapy. Neutropenia, reported in up to 72% of cases, often requires dose reductions or delays. Granulocyte colony-stimulating factor can be helpful in managing and preventing this toxicity. Anemia is another common toxicity and patients may require transfusions of packed red blood cells. Gastrointestinal toxicities are also common. A tailored regimen of prophylactic antiemetics (2-3 agents) should be initiated before SG infusion. For diarrhea, infectious workup should be considered on a case-by-case basis; patients should start loperamide and fluid/electrolyte replacement if necessary. Severe diarrhea associated with cholinergic syndrome should prompt the administration of atropine. Fatigue occurs in approximately half of the patients receiving SG, and <50% of patients experience complete alopecia during treatment. The approval of SG has significantly improved treatment outcomes; however, effective management of the toxicities is critical to optimize patient care and treatment adherence.
Topics: Humans; Antigens, Neoplasm; Camptothecin; Immunoconjugates; Triple Negative Breast Neoplasms; Diarrhea
PubMed: 37800595
DOI: 10.1080/14712598.2023.2267975 -
Frontiers in Public Health 2023Myopia has significantly risen in East and Southeast Asia, and the pathological outcomes of this condition, such as myopic maculopathy and optic neuropathy linked to... (Review)
Review
Myopia has significantly risen in East and Southeast Asia, and the pathological outcomes of this condition, such as myopic maculopathy and optic neuropathy linked to high myopia, have emerged as leading causes of irreversible vision loss. Addressing this issue requires strategies to reduce myopia prevalence and prevent progression to high myopia. Encouraging outdoor activities for schoolchildren and reducing near-work and screen time can effectively prevent myopia development, offering a safe intervention that promotes healthier habits. Several clinical approaches can be employed to decelerate myopia progression, such as administering low-dose atropine eye drops (0.05%), utilizing orthokeratology lenses, implementing soft contact lenses equipped with myopia control features, and incorporating spectacle lenses with aspherical lenslets. When choosing an appropriate strategy, factors such as age, ethnicity, and the rate of myopia progression should be considered. However, some treatments may encounter obstacles such as adverse side effects, high costs, complex procedures, or limited effectiveness. Presently, low-dose atropine (0.05%), soft contact lenses with myopia control features, and orthokeratology lenses appear as promising options for managing myopia. The measures mentioned above are not necessarily mutually exclusive, and researchers are increasingly exploring their combined effects. By advocating for a personalized approach based on individual risk factors and the unique needs of each child, this review aims to contribute to the development of targeted and effective myopia prevention strategies, thereby minimizing the impact of myopia and its related complications among school-aged children in affected regions.
Topics: Humans; Child; Atropine; Ethnicity; Myopia; Research Personnel
PubMed: 37655278
DOI: 10.3389/fpubh.2023.1226438