Effective bolus dose of remimazolam for i-gel® insertion in nonparalyzed patients: a dose-finding study.

PURPOSE: Remimazolam is a recently developed ultra-short-acting benzodiazepine used for anesthesia induction and maintenance. Nevertheless, the effective bolus dose of remimazolam for i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK) insertion without the use of neuromuscular blocking agents (NMBAs) has not been well established. METHODS: This study included 25 adult patients scheduled for surgery under general anesthesia who were eligible for i-gel use. Anesthesia was induced with predetermined bolus doses of remimazolam, starting at 0.3 mg·kg-1 for the first patient, without the use of NMBAs. All patients concurrently received remifentanil using target-controlled infusion (TCI) at a fixed effect-site concentration (Ce) of 3.0 ng·mL-1. Insertion of the i-gel was attempted 90 sec after remimazolam administration, and insertion conditions were assessed. Subsequent doses of remimazolam were decreased or increased by 0.05 mg·kg-1, depending on the success or failure of i-gel insertion. RESULTS: The mean (standard deviation) 50% effective dose (ED50) of a remimazolam bolus for successful i-gel insertion as determined by the modified Dixon's up-and-down method was 0.100 (0.027) mg·kg-1. The ED50 and ED95 estimated by isotonic regression were 0.111 (83% confidence interval [CI], 0.096 to 0.131) mg·kg-1 and 0.182 (95% CI, 0.144 to 0.195) mg·kg-1, respectively. None of the patients required treatment for hypotension or bradycardia during anesthesia induction. CONCLUSION: Based on the ED95 of remimazolam bolus dose determined in our study, we recommend using 0.182 mg·kg-1 of remimazolam in combination with remifentanil TCI at a Ce of 3.0 ng·mL-1 for successful i-gel insertion without NMBAs in adult patients. This regimen seems effective with a low risk of hemodynamic instability during anesthesia induction. STUDY REGISTRATION: ClinicalTrials.gov ( NCT05298228 ); first submitted 6 March 2022.

RéSUMé: OBJECTIF: Le remimazolam est une benzodiazépine à action ultra-courte récemment mise au point et utilisée pour l'induction et le maintien de l'anesthésie. Toutefois, la dose efficace en bolus de remimazolam pour l'insertion de l'i-gel® (Intersurgical Ltd., Wokingham, Berkshire, Royaume-Uni) sans utiliser de bloqueurs neuromusculaires (BNM) n'a pas été bien établie. MéTHODE: Cette étude a inclus 25 adultes devant bénéficier d'une intervention chirurgicale sous anesthésie générale qui étaient éligibles à l'utilisation d'un i-gel. L'anesthésie a été induite avec des doses prédéterminées en bolus de remimazolam, à partir de 0,3 mg·kg−1 pour la première personne, sans utiliser de BNM. Toutes les personnes anesthésiées ont reçu en parallèle du rémifentanil en perfusion à objectif de concentration à une concentration au site effecteur (Ce) de 3,0 ng·mL−1. L'insertion de l'i-gel a été tentée 90 secondes après l'administration de remimazolam, et les conditions d'insertion ont été évaluées. Les doses subséquentes de remimazolam ont été diminuées ou augmentées de 0,05 mg·kg−1, en fonction du succès ou de l'échec de l'insertion de l'i-gel. RéSULTATS: La dose efficace moyenne (écart type) de 50 % (DE50) d'un bolus de remimazolam pour une insertion réussie de l'i-gel, telle que déterminée par la méthode « up-and-down ¼ de Dixon modifiée, était de 0,100 (0,027) mg·kg−1. Les DE50 et DE95 estimées par régression isotonique étaient de 0,111 (intervalle de confiance [IC] à 83 %, 0,096 à 0,131) mg·kg−1 et 0,182 (IC 95 %, 0,144 à 0,195) mg·kg−1, respectivement. Aucun·e patient·e n'a eu besoin de traitement pour une hypotension ou une bradycardie pendant l'induction de l'anesthésie. CONCLUSION: D'après la DE95 de la dose de remimazolam en bolus déterminée dans notre étude, nous recommandons d'utiliser 0,182 mg·kg−1 de remimazolam en association avec une perfusion à objectif de concentration de rémifentanil à une Ce de 3,0 ng·mL−1 pour réussir l'insertion de l'i-gel sans BNM chez la patientèle adulte. Ce schéma semble efficace avec un faible risque d'instabilité hémodynamique lors de l'induction de l'anesthésie. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05298228); première soumission le 6 mars 2022.

Enhanced Recovery After Surgery for Craniotomies: A Systematic Review and Meta-analysis.

The efficacy of the enhanced recovery after surgery (ERAS) protocols in neurosurgery has not yet been established. We performed a systematic review and meta-analysis of randomized controlled trials to compare the effects of ERAS protocols and conventional perioperative care on postoperative outcomes in patients undergoing craniotomy. The primary outcome was postoperative length of hospital stay. Secondary outcomes included postoperative pain visual analog pain scores, incidence of postoperative nausea and vomiting (PONV), postoperative complications, all-cause reoperation, readmission after discharge, and mortality. A literature search up to August 10, 2023, was conducted using PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. Five studies, including 871 patients, were identified for inclusion in this review. Compared with conventional perioperative care, ERAS protocols reduced the length of postoperative hospital stay (difference of medians, -1.52 days; 95% CI: -2.55 to -0.49); there was high heterogeneity across studies (I2, 74%). ERAS protocols were also associated with a lower risk of PONV (relative risk, 0.79; 95% CI: 0.69-0.90; I2, 99%) and postoperative pain with a visual analog scale score ≥4 at postoperative day 1 (relative risk, 0.37; 95% CI: 0.28-0.49; I2, 14%). Other outcomes, including postoperative complications, did not differ between ERAS and conventional care groups. ERAS protocols may be superior to conventional perioperative care in craniotomy patients in terms of lower length of hospital stay, lower incidence of PONV, and improved postoperative pain scores. Further randomized trials are required to identify the impact of ERAS protocols on the quality of recovery after craniotomy.

Optimizing the maximum reported cluster size for the multinomial-based spatial scan statistic.

BACKGROUND: Correctly identifying spatial disease cluster is a fundamental concern in public health and epidemiology. The spatial scan statistic is widely used for detecting spatial disease clusters in spatial epidemiology and disease surveillance. Many studies default to a maximum reported cluster size (MRCS) set at 50% of the total population when searching for spatial clusters. However, this default setting can sometimes report clusters larger than true clusters, which include less relevant regions. For the Poisson, Bernoulli, ordinal, normal, and exponential models, a Gini coefficient has been developed to optimize the MRCS. Yet, no measure is available for the multinomial model. RESULTS: We propose two versions of a spatial cluster information criterion (SCIC) for selecting the optimal MRCS value for the multinomial-based spatial scan statistic. Our simulation study suggests that SCIC improves the accuracy of reporting true clusters. Analysis of the Korea Community Health Survey (KCHS) data further demonstrates that our method identifies more meaningful small clusters compared to the default setting. CONCLUSIONS: Our method focuses on improving the performance of the spatial scan statistic by optimizing the MRCS value when using the multinomial model. In public health and disease surveillance, the proposed method can be used to provide more accurate and meaningful spatial cluster detection for multinomial data, such as disease subtypes.

A simulation study for geographic cluster detection analysis on population-based health survey data using spatial scan statistics.

BACKGROUND: In public health and epidemiology, spatial scan statistics can be used to identify spatial cluster patterns of health-related outcomes from population-based health survey data. Although it is appropriate to consider the complex sample design and sampling weight when analyzing complex sample survey data, the observed survey responses without these considerations are often used in many studies related to spatial cluster detection. METHODS: We conducted a simulation study to investigate which data type from complex survey data is more suitable for use by comparing the spatial cluster detection results of three approaches: (1) individual-level data, (2) weighted individual-level data, and (3) aggregated data. RESULTS: The results of the spatial cluster detection varied depending on the data type. To compare the performance of spatial cluster detection, sensitivity and positive predictive value (PPV) were evaluated over 100 iterations. The average sensitivity was high for all three approaches, but the average PPV was higher when using aggregated data than when using individual-level data with or without sampling weights. CONCLUSIONS: Through the simulation study, we found that use of aggregate-level data is more appropriate than other types of data, when searching for spatial clusters using spatial scan statistics on population-based health survey data.

Height outcomes in Korean children with idiopathic short stature receiving growth hormone treatment.

Objectives: Growth hormone (GH) therapy's capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment. Methods: We retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis. Results: We included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2-3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device. Conclusion: ISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS.

Optimizing the maximum reported cluster size in the spatial scan statistic for survival data.

BACKGROUND: The spatial scan statistic is a useful tool for cluster detection analysis in geographical disease surveillance. The method requires users to specify the maximum scanning window size or the maximum reported cluster size (MRCS), which is often set to 50% of the total population. It is important to optimize the maximum reported cluster size, keeping the maximum scanning window size at as large as 50% of the total population, to obtain valid and meaningful results. RESULTS: We developed a measure, a Gini coefficient, to optimize the maximum reported cluster size for the exponential-based spatial scan statistic. The simulation study showed that the proposed method mostly selected the optimal MRCS, similar to the true cluster size. The detection accuracy was higher for the best chosen MRCS than at the default setting. The application of the method to the Korea Community Health Survey data supported that the proposed method can optimize the MRCS in spatial cluster detection analysis for survival data. CONCLUSIONS: Using the Gini coefficient in the exponential-based spatial scan statistic can be very helpful for reporting more refined and informative clusters for survival data.

Visible-Light-Induced Trifluoromethylation of Unactivated Alkenes with Tri(9-anthryl)borane as an Organophotocatalyst.

Tri(9-anthryl)borane was successfully applied as an organophotocatalyst for the visible-light-induced trifluoromethylation of unactivated alkenes with CF3I. The mild reaction conditions tolerated a variety of functional groups, and the reaction could be extended to perfluoroalkylations with C3F7I and C4F9I. Mechanistic studies revealed that the photoredox catalysis involves an oxidative quenching pathway.

Visible-light-induced installation of oxyfluoroalkyl groups.

(Hetero)aryloxytetrafluoroethylation of heteroaromatics and alkenes has been achieved by visible-light photocatalysis utilizing readily synthesized oxyfluoroalkyl reagents. The mild reaction conditions and the high diversity on both substrates and oxyfluoroalkyl reagents make this a useful method for late-stage modifications in the development of various functional molecules.