Minimum Atropine Dosing in Pediatric Patients: Does CRNA Practice Reflect Current Recommendations?

The purpose of this study was to evaluate certified registered nurse anesthetist (CRNA) current pediatric atropine dosing practices. Emphasis was placed on rationale for dosing and knowledge regarding current literature and guidelines. An electronic survey was deployed by the American Association of Nurse Anesthetists (AANA)'s survey department to a total of 2,905 CRNAs who are current AANA members. The survey was completed by 98 CRNAs, of which 67 selected that they do not administer anesthesia to pediatric patients weighing less than 5 kg and were excluded from further survey participation. The responses from the remaining 31 CRNAs were utilized for data analysis (n = 31). Approximately two thirds of participants (64.5%) were unaware of available guidelines pertaining to pediatric dosing of atropine within the last 5 years. A statistically significant difference existed when analyzing whether awareness of guidelines was associated with knowledge of the correct American Heart Association recommended pediatric atropine dose. Providers who were aware of guidelines reported the correct dose 100% of the time, whereas those unaware of guidelines reported the correct dose only 65% of the time (P = .03). Variability in clinical practices and sources guiding practice should be addressed to avoid potential overdosing in the vulnerable neonatal population.

The Relationship between Resistance Training Frequency and Muscle Quality in Adolescents.

Previous research has established the role of resistance training (RT) on muscle function in adolescents, but a lack of evidence to optimize RT for enhancing muscle quality (MQ) exists. This study examined whether RT frequency is associated with MQ in a nationally representative adolescent cohort. A total of 605 adolescents (12−15 year) in NHANES were stratified based on RT frequency. MQ was calculated as combined handgrip strength divided by arm lean mass (via dual-energy X-ray absorptiometry). Analysis of covariance was adjusted for sex, race/ethnicity, and arm fat percentage; p < 0.05 was considered significant. RT frequency was associated with MQ for 2−7 day/week but not 1 day/week. When no RT was compared to 1−2 and 3−7 day/week, associations were present for 3−7 day/week but not 1−2 day/week. When comparing no RT to 1−4 and 5−7 day/week, associations existed for 5−7 day/week but not 1−4 day/week. Next, no RT was compared to 1, 2−3, and 4−7 day/week; associations were found for 4−7 day/week, while 2−3 day/week had a borderline association (p = 0.06); there were no associations for 1 day/week. Finally, no RT was compared to 1, 2, 3, 4, and 5−7 day/week; associations were present for all except 1 and 3 day/week. These prospective data suggest a minimum RT frequency of 2 day/week is associated with MQ in adolescents as indicated by the lack of differences in MQ between 1 day/week RT versus no RT.

Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry. RESULTS: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment. CONCLUSION: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

The Minimum Effective Training Dose Required for 1RM Strength in Powerlifters.

The aim of this multi-experiment paper was to explore the concept of the minimum effective training dose (METD) required to increase 1-repetition-maximum (1RM) strength in powerlifting (PL) athletes. The METD refers to the least amount of training required to elicit meaningful increases in 1RM strength. A series of five studies utilising mixed methods, were conducted using PL athletes & coaches of all levels in an attempt to better understand the METD for 1RM strength. The studies of this multi-experiment paper are: an interview study with elite PL athletes and highly experienced PL coaches (n = 28), an interview and survey study with PL coaches and PL athletes of all levels (n = 137), two training intervention studies with intermediate-advanced PL athletes (n = 25) and a survey study with competitive PL athletes of different levels (n = 57). PL athletes looking to train with a METD approach can do so by performing ~3-6 working sets of 1-5 repetitions each week, with these sets spread across 1-3 sessions per week per powerlift, using loads above 80% 1RM at a Rate of Perceived Exertion (RPE) of 7.5-9.5 for 6-12 weeks and expect to gain strength. PL athletes who wish to further minimize their time spent training can perform autoregulated single repetition sets at an RPE of 9-9.5 though they should expect that strength gains will be less likely to be meaningful. However, the addition of 2-3 back-off sets at ~80% of the single repetitions load, may produce greater gains over 6 weeks while following a 2-3-1 squat-bench press-deadlift weekly training frequency. When utilizing accessory exercises in the context of METD, PL athletes typically utilize 1-3 accessory exercises per powerlift, at an RPE in the range of 7-9 and utilize a repetition range of ~6-10 repetitions.

Hypofractionated spinal stereotactic body radiation therapy for high-grade epidural disease.

OBJECTIVE: To characterize the clinical outcomes when stereotactic body radiation therapy (SBRT) alone is used to treat high-grade epidural disease without prior surgical decompression, the authors conducted a retrospective cohort study of patients treated at the Memorial Sloan Kettering Cancer Center between 2014 and 2018. The authors report locoregional failure (LRF) for a cohort of 31 cases treated with hypofractionated SBRT alone for grade 2 epidural spinal cord compression (ESCC) with radioresistant primary cancer histology. METHODS: High-grade epidural disease was defined as grade 2 ESCC, which is notable for radiographic deformation of the spinal cord by metastatic disease. Kaplan-Meier survival curves and cumulative incidence functions were generated to examine the survival and incidence experiences of the sample level with respect to overall survival, LRF, and subsequent requirement of vertebral same-level surgery (SLS) due to tumor progression or fracture. Associations with dosimetric analysis were also examined. RESULTS: Twenty-nine patients undergoing 31 episodes of hypofractionated SBRT alone for grade 2 ESCC between 2014 and 2018 were identified. The 1-year and 2-year cumulative incidences of LRF were 10.4% (95% CI 0-21.9) and 22.0% (95% CI 5.5-38.4), respectively. The median survival was 9.81 months (95% CI 8.12-18.54). The 1-year cumulative incidence of SLS was 6.8% (95% CI 0-16.0) and the 2-year incidence of SLS was 14.5% (95% CI 0.6-28.4). All patients who progressed to requiring surgery had index lesions at the thoracic apex (T5-7). CONCLUSIONS: In carefully selected patients, treatment of grade 2 ESCC disease with hypofractionated SBRT alone offers a 1-year cumulative incidence of LRF similar to that in low-grade ESCC and postseparation surgery adjuvant hypofractionated SBRT. Use of SBRT alone has a favorable safety profile and a low cumulative incidence of progressive disease requiring open surgical intervention (14.5%).

Pelvic radiation therapy with volumetric modulated arc therapy and intensity-modulated radiotherapy after renal transplant: A report of 3 cases.

AIM: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. BACKGROUND: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. MATERIALS AND METHODS: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. CASES DESCRIPTION: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). CONCLUSION: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.

Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin.

OBJECTIVE: Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers. METHODS: A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method. RESULTS: A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/ß = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%). CONCLUSIONS: Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

Fluconazole induces genotoxicity in cultured human peripheral blood mononuclear cells via immunomodulation of TNF-α, IL-6, and IL-10: new challenges for safe therapeutic regimens.

Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown. Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole. Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120 µg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris® and LAZAR® programs). Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30 µg/mL) and 6 µg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays. Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.

Reduction of fluoroscopy dose for cardiac electrophysiology procedures: A feasibility and safety study.

BACKGROUND: Exposure to high doses of radiation during cardiac interventional procedures is associated with increased rates of cataract and cancer in patients and staff members. Thus, reduction of radiation is recommended by international medical societies. The aim of this study was to evaluate, if the lowest reasonable fluoroscopic acquisition setting for electrophysiological procedures using a novel X-ray detector operated at a minimum detector entrance dose per fluoroscopy pulse is feasible and safe. METHODS: 641 consecutive patients (407 m/234f) underwent ablation procedures at our institution between August 2015 and December 2017. All ablations were performed using an Artis Q.zen X-ray system (Siemens, Germany). The first 308 patients were treated using the conventional dose program ("fluoroscopy zen standard"), from October 2016 until December 2017 another 333 patients underwent ablations using the optimized X-ray dosing program "fluoroscopy zen ULD". For the standard program fluoroscopy dose was set to 18nGy/f, for the minimized dosing program the dose was set to 6nGy/pulse and could be increased to 10 or 15 nGy/pulse manually. RESULTS: A total of 213 AV-node reentry tachycardia (AVNRT), 73 accessory pathways (AP), 71 atrial flutter and 284 atrial fibrillation (AF) ablation procedures were performed. Pulmonary vein isolation was performed using an electroanatomic mapping system (CARTO, Biosense Webster, USA) in 117 or a cryoballoon (Cryocath Medtronic, USA) in 167 patients. Total area dose could be reduced in all groups by a mean of 74.7% (4201.4µGym² vs. 1063.7µGym²), with a relative reduction of 73.1% for left atrial and 78.0% for right sided ablations. Total fluoroscopy time, procedure duration, acute ablation success, recurrence rate and complications remained unchanged. CONCLUSION: Fluoroscopy dose could be significantly reduced using an optimized X-ray dosing program in a novel X-ray detector without increasing total fluoroscopy time and without alterations of the incidence of recurrences or complications.

Principios filosóficos de la homeopatía / Philosophical principles of homeopathy

De una manera clara, directa y muy didáctica, los autores de este trabajo realizan un recorrido por los principios que configuran la estructura de la filosofía homeopática, rescatando muchos de los conceptos inscritos en algunas de las obras literarias del célebre Higinio G. Pérez, fundador de la Escuela Libre de Homeopatía, y del fisiólogo norteamericano Walter Bradford Cannon, los cuales, por supuesto, son coincidentes con muchos de los preceptos hipocráticos y hahnemaniannos. Para complementar su análisis, los investigadores refieren las opiniones de algunos otros científicos (fisiólogos y biólogos) y citan de manera textual diversos parágrafos del doctor Samuel Hahnemann, al tiempo que expresan su opinión sobre la vigencia de dichas premisas en la época moderna. (AU)

In a clear direct and very didactic manner the authors of this paper perform a journey by the principles that configure the philosophical structure of homeopathy, recovering many of the concepts written in various of the literary works of the notorious physician Higinio G. Pérez, founder of the Homeopathic Free Scholl and from the north American physiologist Walter Bradford Cannon, which of course, are coincidental with most of the Hippocratic an Hanemanniann precepts. In order to complete their analysis, these researchers refer the opinions of some other scientists (Physiologist and Biologists) and quoted verbatim various paragraphs of Dr. Samuel Hahnemann, at the same time, that they state their personal opinion on the validity of these assumptions in modern times. (AU)

Principios filosóficos de la homeopatía / Philosophical principles of homeopathy

De una manera clara, directa y muy didáctica, los autores de este trabajo realizan un recorrido por los principios que configuran la estructura de la filosofía homeopática, rescatando muchos de los conceptos inscritos en algunas de las obras literarias del célebre Higinio G. Pérez, fundador de la Escuela Libre de Homeopatía, y del fisiólogo norteamericano Walter Bradford Cannon, los cuales, por supuesto, son coincidentes con muchos de los preceptos hipocráticos y hahnemaniannos. Para complementar su análisis, los investigadores refieren las opiniones de algunos otros científicos (fisiólogos y biólogos) y citan de manera textual diversos parágrafos del doctor Samuel Hahnemann, al tiempo que expresan su opinión sobre la vigencia de dichas premisas en la época moderna...

In a clear direct and very didactic manner the authors of this paper perform a journey by the principles that configure the philosophical structure of homeopathy, recovering many of the concepts written in various of the literary works of the notorious physician Higinio G. Pérez, founder of the Homeopathic Free Scholl and from the north American physiologist Walter Bradford Cannon, which of course, are coincidental with most of the Hippocratic an Hanemanniann precepts. In order to complete their analysis, these researchers refer the opinions of some other scientists (Physiologist and Biologists) and quoted verbatim various paragraphs of Dr. Samuel Hahnemann, at the same time, that they state their personal opinion on the validity of these assumptions in modern times...