Citations

AbstractObjectiveNeed for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement.MethodsThis phase 3, open‐label, repeat‐dose, safety study of diazepam nasal spray enrolled patients (6‐65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (<2, moderate frequency; 2‐5, high frequency; >5, very‐high frequency). Safety was evaluated based on treatment‐emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness.ResultsOf 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment‐related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate‐, high‐, and very‐high‐frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use.SignificanceFrequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of <2 to >5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.

Abstract Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P &lt; 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P &lt; 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.

Abstract Objective Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods A long‐term, phase 3, open‐label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no‐benzodiazepine group. Findings were similar in a sub‐analysis of patients who were ( n = 44) or were not ( n = 75) taking clobazam. Significance This analysis of patients from a long‐term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub‐analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

Abstract Background Appendiceal cancers represent a diverse group of malignancies with varying biological behavior. The significance of lymph node metastases in relation to long‐term survival and chemotherapy response is poorly defined. Methods The National Cancer Database was queried to find patients diagnosed with appendiceal cancer from 1998 to 2012. Kaplan–Meier curves and multivariable Cox regression analyses were used to study the association between lymph node status and overall survival. Stage IV patients were excluded. Results The rate of nodal positivity of the 9841 patients with known node status was: signet ring 47.4%, carcinoid 42.3%, nonmucinous adenocarcinoma 28.8%, goblet cell 21.9%, and mucinous adenocarcinoma 20.4%. Node‐positive patients had worse long‐term survival for all subtypes with the exception of carcinoid tumors ( p < 0.001). The strongest association was for signet cell and goblet cell. Adjuvant chemotherapy in node‐positive patients improved survival for mucinous, nonmucinous, and signet ring cell histology ( p < 0.01), but not for goblet cell. Conclusions Nodal involvement in patients with appendiceal cancer varies in incidence, association with adverse survival, and response to systemic therapy. Individualized treatment algorithms for the management of the subtypes of appendiceal cancer are needed.

Objective The aim of the study was to determine the prevalence of second victim experience (SVE) among obstetrics and gynecology (OBGYN) clinical and nonclinical healthcare workers and compare healthcare workers who did and did not identify as a second victim (SV) in the last year. Methods The validated Second Victim Experience and Support Tool and additional questions designed to explore SVE topics specific to OBGYN healthcare workers were administered to a multidisciplinary group. Results Of 571 individuals sent a survey link, 205 completed the survey: 117 worked in obstetrics (OB), 73 in gynecology (GYN), and 15 in both areas. Overall, 44.8% of respondents identified as an SV sometime during their career, 18.8% within the last 12 months. Among nonclinical staff respondents, 26.7% identified as an SV during their career and 13.3% in the last 12 months. Respondents who identified as an SV in the last 12 months reported experiencing significantly more psychological and physical distress, a greater degree to which colleague and institutional support were perceived as inadequate, decreased professional self-efficacy, and increased turnover intentions. The most common events identified as likely triggers for SVE were fetal or neonatal loss (72.7%) and maternal death (68.2%) in OB and patient accusations or complaints (69.3%) in GYN. Conclusions Among survey respondents, there was a high prevalence of SVs in OBGYN staff, distributed equally between OB and GYN. Nonclinical healthcare workers also identified as SVs. The OBGYN departments should consider using the Second Victim Experience and Support Tool to screen for potential SV among their healthcare workers to provide additional support after events.

Objective: To report the injury characteristics, radiographic findings, and long-term outcomes of nonoperative management for posterior shoulder instability (PSI). Design: A retrospective review of 143 patients with PSI using a large geographic database. Setting: Single county between January 1994 and July 2012. Patients: A clinical history and diagnosis of PSI, one confirmatory imaging study to support the diagnosis, and a minimum of 5 years follow-up were required for inclusion. Patients with seizure disorders, anterior-only instability, multidirectional instability, and superior labrum from anterior to posterior diagnosis were excluded. Interventions: Patients with PSI were managed nonoperatively or operatively. Main Outcome Measures: Pain, recurrent instability, and progression into glenohumeral osteoarthritis at long-term follow-up. Results: One hundred fifteen patients were identified. Thirty-seven (32%) underwent nonoperative management. Twenty (54%) patients were diagnosed with posterior subluxation, 3 (8%) with a single dislocation, and 7 (19%) with multiple dislocations. Symptomatic progression of glenohumeral arthritis was observed in 8% (3) of patients. Pain improved in 46% (17) of patients and worsened in 19% (7). Recurrent instability and progression to osteoarthritis occurred in 15% (3/20) of patients with a traumatic instability event compared with 0% of atraumatic patients after nonoperative management ( P = 0.234). Pain at follow-up was more common in nonoperative than operative patients ( P = 0.017). Conclusions: Nonoperative management is a viable option for many patients with posterior shoulder instability; however, many may continue to have posterior shoulder pain.

Oesophageal cancer is categorised among the most fatal cancers across the world with a mortality ranking of sixth position. Chemotherapy with FOLFOX—a regimen of fluorouracil, leucovorin, and oxaliplatin—has been approved in the treatment of oesophageal cancer owing to its lower toxicity compared with the previous regimens. We report the first case of a patient with oesophageal cancer metastatic to the hyoid presenting with sudden-onset shortness of breath and anterior neck swelling secondary to treatment with FOLFOX-6. CT was notable for subglottic soft-tissue swelling and cystic necrosis of the hyoid bone tumour, and the patient subsequently required placement of a definitive airway via tracheostomy. This case illustrates the importance of anticipating the need for pre-emptive tracheostomy in patients with hyoid bone tumours receiving treatment with FOLFOX.