Background

Emergency physicians regularly encounter agitated patients. In extremely agitated and violent patients, the onset of many traditional medications is relatively slow and often requires additional medication. Ketamine is frequently used in emergency departments (EDs) for procedural sedation and intubation, but has recently been suggested as a treatment for acute agitation.

Objectives

We sought to examine the use of ketamine in the treatment of acute agitation in an ED setting, including vital sign changes as a result of this medication.

Methods

This is a structured review of an historical cohort of patients over 7 years at two university EDs. Patients were included if they received ketamine as treatment for acute agitation. Abstracted data included age, vital signs including hypoxia, any additional medications for agitation, and alcohol/drug intoxication.

Results

Ketamine was administered for agitation on 32 visits involving 27 patients. Preadministration systolic blood pressure was 131 ± 20 mm Hg, with an average postadministration increase of 17 ± 25 mm Hg. The average baseline heart rate was 98 ± 23 beats/min, with an average increase of 8 ± 17 beats/min. No patients became hypoxic; 62.5% of patients required additional calming medication. Alcohol or drug intoxication was present in 40.6% of patients.

Conclusions

We found ketamine was used rarely, but had few major adverse effects on vital signs even in a population with 21.9% alcohol intoxication. However, a high proportion (62.5%) of patients required additional pharmacologic treatment for agitation, implying that administering ketamine is useful only for initial control of severe agitation.

Background

Although first-generation antipsychotics (FGAs) have long been used in the emergency department (ED) to treat acute agitation, little is known about how these medications are used in modern clinical practice. In particular, little work has been published about whether ED clinicians administer FGAs with adjunctive medications in accordance with expert guidelines or the prescribing practices of FGAs over time.

Objectives

1) To provide a comparison of the frequency with which FGAs are administered with adjunctive benzodiazepines or anticholinergic medications. 2) To analyze the prescribing trends for FGAs over time, particularly in the years after the U.S. Food and Drug Administration (FDA) black-box warning for droperidol.

Methods

This is a structured review of a retrospective cohort of patients receiving haloperidol or droperidol in two EDs over a 7-year period.

Results

Haloperidol or droperidol was administered on 2833 patient visits during the study period, with haloperidol being administered most often. Adjunctive medications are administered less than half of the time. The use of droperidol has remained relatively static, whereas the use of haloperidol has increased.

Conclusions

First-generation antipsychotics are still widely utilized in the ED. When administered, these medications are used with adjunctive medications that may decrease side effects less than half of the time. Droperidol use has remained unchanged in the years after the FDA black-box warning, whereas use of haloperidol has continued to rise.

Background and purpose

The risk of genitourinary (GU) toxicity is dose-limiting in radiotherapy (RT) for prostate cancer. This study investigated whether motion-inclusive spatial dose/volume metrics explain the GU toxicity manifesting after high-precision RT for prostate cancer.

Material and methods

A matched case-control was performed within a cohort of 258 prostate cancer patients treated with daily cone-beam CT (CBCT)-guided RT (prescription doses of 77.4-81.0 Gy). Twenty-seven patients (10.5%) presented late RTOG GU ≥ Grade 2 toxicity and those without symptoms of toxicity prior treatment (N = 7) were selected as cases. Each case was matched with three controls based on pre-treatment GU symptoms, age, Gleason score, follow-up time, and hormone therapy. Thirteen CBCTs per patient were rigidly registered to the planning CT using the recorded treatment shifts, and the bladder was manually contoured on each CBCT. Planned and actually delivered dose/volume metrics (the latter averaged across the CBCTs) were extracted from the bladder and its subsectors, and compared between cases and controls (two-way ANOVA test).

Results

There were no significant differences between planned and delivered dose/volume metrics; also, there were no significant differences between cases and controls at any dose level, neither for planned nor delivered doses. The cases tended to have larger bladder volumes during treatment than controls (221 ± 71 cm³ vs 166 ± 73 cm³; p = 0.09).

Conclusions

High-precision RT for prostate cancer eliminates differences between planned and delivered dose distributions. Neither planned nor delivered bladder dose/volume metrics were associated to the remaining low risk of developing GU toxicity after high-precision radiotherapy for prostate cancer.

Background

Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest.

Methods

Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes.

Results

In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence.

Conclusions

This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches.