Frequency of cardiotoxicity following intramuscular administration of epinephrine in emergency department patients with anaphylaxis.

Objectives: Epinephrine can be a life-saving treatment for patients with anaphylaxis. Potential cardiovascular side effects of epinephrine may contribute to clinician hesitancy to use it. However, the frequency of cardiotoxicity resulting from epinephrine treatment for anaphylaxis is not well described. We sought to describe the frequency of cardiotoxicity following intramuscular (IM) administration of epinephrine in adult emergency department (ED) patients with anaphylaxis. Methods: We conducted a retrospective observational study at a single, quaternary care academic ED in Tennessee. We identified consecutive ED visits with the diagnosis of anaphylaxis from 2017 to 2021 who received at least one intramuscular (IM) dose of epinephrine in the ED. Analysis was primarily descriptive. The primary outcome was cardiotoxicity, the occurrence of any of the following after epinephrine administration: ischemic electrocardiogram changes, systolic blood pressure >200 mmHg, or cardiac arrest ≤4 h; elevated troponin ≤12 h; or percutaneous coronary intervention or depressed ejection fraction ≤72 h. Results: Among 338 included patients, 16 (4.7%; 95%CI: 2.8-7.6%) experienced cardiotoxicity. Cardiotoxic events included eight (2.4%) ischemic electrocardiogram changes, six (1.8%) episodes of elevated troponin, five (1.5%) atrial arrhythmias, one (0.3%) ventricular arrythmia, and one (0.3%) depressed ejection fraction. Patients with cardiotoxicity were significantly older, had more comorbidities, and were more likely to have received multiple doses of epinephrine or an epinephrine infusion compared with a single IM dose of epinephrine. Conclusions: Among 338 consecutive adult ED patients who received IM epinephrine for anaphylaxis during a recent 4-year period, cardiotoxic side effects were observed in approximately 5% of patients.

Correction: Joseph et al. Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report. Pharmaceuticals 2023, 16, 1164.

In the original publication [...].

Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report.

Intravenous (IV) ketamine and FDA-approved intranasal (IN) esketamine are increasingly used for treatment-resistant depression (TRD). Preliminary studies have suggested a synergistic effect of ketamine and lamotrigine, although the data are inconclusive. Herein, we report the response to serial ketamine/esketamine treatment among patients with TRD with or without lamotrigine therapy. In this historical cohort study, we included adult patients with TRD who received serial IV racemic ketamine (0.5 mg/kg over 40-100 min) or IN esketamine (56/84 mg) treatments. A change in depressive symptoms was assessed using the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) scale. There were no significant differences in response or remission rates among the patients on or not on lamotrigine during the ketamine/esketamine treatments. For a percent change in the QIDS-SR from baseline, no interaction was found between the lamotrigine groups and treatment number (p = 0.70), nor the overall effect of the group (p = 0.38). There was a trend towards lower dissociation (based on the CADSS score) among current lamotrigine users, especially in patients who received IV ketamine. A major limitation is the limited number of patients taking lamotrigine (n = 13). This preliminary study provides insufficient evidence that continuing lamotrigine therapy attenuates the antidepressant effect of repeated ketamine/esketamine; however, there seems to be a signal toward attenuating dissociation with lamotrigine in patients receiving serial ketamine treatments. Further observational studies or randomized controlled trials are needed to replicate these findings.

Patient Satisfaction and Acoustic Changes in Trans Women after Gender Affirming Voice Training.

OBJECTIVES: Gains in pitch from gender affirming voice training (GVT) alone in trans women have historically been shown to decline after 1 year. Currently no standard exists for length and type of GVT that yields meaningful behavioral change and patient satisfaction with voice outcomes in trans women. This study aims to determine whether GVT alone leads to sustained pitch elevation and patient satisfaction in trans women. METHODS: Retrospective review from 2016 to 2020 of trans women patients who underwent GVT alone for voice change. Charts were reviewed for acoustic analysis of pitch including sustained vowel fundamental frequency, speaking fundamental frequency, and quality of life data from the Trans Woman Voice Questionnaire at pre-therapy, immediate post-therapy, and extended post-therapy time intervals. RESULTS: A total of 157 patients presented to our Voice Center, of which 34 participated in the full course of GVT. Patients underwent an average of six sessions of GVT (range 5-7) over an average of 13.14 weeks (range 6-16). Average time between completing GVT and presenting for extended follow-up was 11.37 months (range 6-31). Compared to initial presentation prior to therapy, at extended follow-up after completing GVT average change in F0/a/, SF0, and TWVQ were 64.6 Hz, 31.3 Hz, and 32.45. No significant change was noted between immediate post-therapy and extended post-therapy acoustic measures. TWVQ demonstrated continued improvement between immediate post-therapy and extended post-therapy. CONCLUSIONS: In self-selected patients who present for extended follow-up, GVT alone can result in sustained pitch elevation and voice-related quality life in trans women. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2340-2345, 2023.

1-Year Results of Combined Modified Wendler Glottoplasty with Voice Therapy in Transgender Women.

BACKGROUND: To date, 1-year evaluation of pitch elevation in patients undergoing modified Wendler glottoplasty (WG) in combination with VT has not been assessed. OBJECTIVES: To determine whether 1-year pitch elevation is sustained in patients who undergo modified WG in combination with VT for voice feminization. METHODS: A retrospective review of patients who underwent WG in combination with voice therapy (VT) was performed from 2016 to 2020. Charts were reviewed for sustained vowel fundamental frequency (F0/a/), speaking fundamental frequency (SF0), and Trans Woman Voice Questionnaire (TWVQ) at preoperative, initial postoperative (3-6 months after surgery), and 12-month postoperative visits. RESULTS: Change in average F0/a/, SF0 and TWVQ was 50.25 Hz, 32.96 Hz, and 32.6 at 12-months postoperatively compared to preoperative values. Initial and 12-month postoperative SF0 were significantly higher than preoperative SF0 (Mann-Whitney U test p = 0.0042, p = 0.0010). There was no difference in initial postoperative and 12-month postoperative SF0 (p = 0.50). TWVQ at 12 months was significantly lower than preoperative TWVQ (ANOVA p < 0.001, Tukey honestly significant difference HSD p < 0.05). CONCLUSIONS: Pitch elevation remains sustained at one year in patients undergoing modified WG in combination with VT. Modified Wendler glottoplasty combined with VT results in relatively long-term improvements in voice-related quality of life and is possibly a beneficial addition in the long-term management of patients who desire voice feminization. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:615-620, 2023.

Predictive values of static endoscopic evaluation of swallowing in adults.

OBJECTIVE: Static endoscopic evaluation of swallowing (SEES) is an instrumental evaluation developed for in-office identification of patients who may benefit from a modified barium swallow study (MBSS). We aim to determine the predictive value of SEES for evaluating dysphagia. METHODS: A retrospective case series was performed on adults evaluated for dysphagia using SEES followed by MBSS at a single tertiary care center. Studies were evaluated by two blinded expert raters. RESULTS: Fifty-eight patients were included. Thin liquid penetration on SEES had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.86 (95% CI 0.70-0.95), 0.63 (95% CI 0.24-0.91), 0.91 (95% CI 0.76-0.98), and 0.5 (0.19-0.81), respectively, for predicting thin liquid penetration on MBSS, and 1.0 (95% CI 0.59-1.0), 0.29 (95% CI 0.15-0.47), 0.23 (95% CI 0.10-0.41), and 1.0 (95% CI 0.69-1.0) for predicting thin liquid aspiration on MBSS. Thin liquid aspiration on SEES had a sensitivity, specificity, PPV, and NPV of 0.67 (95% CI 0.09-0.99), 0.85 (95% CI 0.66-0.96), 0.33 (95% CI 0.04-0.78), and 0.96 (95% CI 0.79-1.0), respectively, for predicting thin liquid aspiration on MBSS. CONCLUSIONS: SEES may be used as an objective in-office test to screen for aspiration and penetration. Thin liquid penetration on SEES is moderately sensitive for predicting penetration on MBSS. Absence of thin liquid penetration or aspiration on SEES has a high NPV for excluding aspiration on MBSS. Abnormalities on SEES or the need to view the entire swallowing mechanism should prompt an MBSS for a more complete evaluation of dysphagia.Level of Evidence: 4.

Quality Measurement and Patient Outcomes in Inpatient Behavioral Health: Assessing the Current Framework.

ABSTRACT: Quality measurement across healthcare is undertaken with a goal of improving care and outcomes for patients; however, the relationship between quality measurement and patient outcomes remains largely untested, particularly in inpatient behavioral health. Using a retrospective quantitative design, we assessed 142 behavioral health organizations' quality data submitted to the Hospital-Based Inpatient Psychiatric Services and Inpatient Psychiatric Facility Quality Reporting programs from 2017 to 2018 and tested relationships between compliance on 16 quality measures and symptom improvement on patient self-report outcomes (SROs) at the facility level. Performance on many quality measures was negatively skewed (at least four have almost no room for improvement on average), and there was high interrelatedness between most quality measures. Nine of the assessed measures correlated with patient SROs but not in clear groupings. Findings indicate that an underlying organizational construct may be driving compliance rates on quality measures, but the measures are not linked to treatment outcomes as expected. We encourage an expansion of the current framework of behavioral health quality measurement beyond process and organization and suggest the addition of patient outcomes such as SROs as quality measures to directly assess patient improvement.

Sequencing Red Fox Y Chromosome Fragments to Develop Phylogenetically Informative SNP Markers and Glimpse Male-Specific Trans-Pacific Phylogeography.

The red fox (Vulpes vulpes) has a wide global distribution with many ecotypes and has been bred in captivity for various traits, making it a useful evolutionary model system. The Y chromosome represents one of the most informative markers of phylogeography, yet it has not been well-studied in the red fox due to a lack of the necessary genomic resources. We used a target capture approach to sequence a portion of the red fox Y chromosome in a geographically diverse red fox sample, along with other canid species, to develop single nucleotide polymorphism (SNP) markers, 13 of which we validated for use in subsequent studies. Phylogenetic analyses of the Y chromosome sequences, including calibration to outgroups, confirmed previous estimates of the timing of two intercontinental exchanges of red foxes, the initial colonization of North America from Eurasia approximately half a million years ago and a subsequent continental exchange before the last Pleistocene glaciation (~100,000 years ago). However, in contrast to mtDNA, which showed unidirectional transfer from Eurasia to North America prior to the last glaciation, the Y chromosome appears to have been transferred from North America to Eurasia during this period. Additional sampling is needed to confirm this pattern and to further clarify red fox Y chromosome phylogeography.

Genome-wide genetic variation coupled with demographic and ecological niche modeling of the dusky-footed woodrat (Neotoma fuscipes) reveal patterns of deep divergence and widespread Holocene expansion across northern California.

Understanding how species have responded to past climate change may help refine projections of how species and biotic communities will respond to future change. Here, we integrate estimates of genome-wide genetic variation with demographic and niche modeling to investigate the historical biogeography of an important ecological engineer: the dusky-footed woodrat, Neotoma fuscipes. We use RADseq to generate a genome-wide dataset for 71 individuals from across the geographic distribution of the species in California. We estimate population structure using several model-based methods and infer the demographic history of regional populations using a site frequency spectrum-based approach. Additionally, we use ecological niche modeling to infer current and past (Last Glacial Maximum) environmental suitability across the species' distribution. Finally, we estimate the directionality and possible spatial origins of regional population expansions. Our analyses indicate this species is subdivided into three regionally distinct populations, with the deepest divergence occurring ~1.7 million years ago across the modern-day San Francisco-Bay Delta region; a common biogeographic barrier for the flora and fauna of California. Our models of environmental suitability through time coincide with our estimates of population expansion, with relative long-term stability in the southern portion of the range, and more recent expansion into the northern end of the range. Our study illustrates how the integration of genome-wide data with spatial and demographic modeling can reveal the timing and spatial extent of historic events that determine patterns of biotic diversity and may help predict biotic response to future change.

Effect of Wendler Glottoplasty on Acoustic Measures of Voice.

OBJECTIVES: Voice therapy has been the primary treatment for voice feminization in transfemale patients due to concerns that surgery worsens voice quality. We aim to determine the impact of Wendler glottoplasty on acoustic measures of voice. STUDY DESIGN: Retrospective case series. METHODS: Transgender female patients treated for vocal feminization with Wendler glottoplasty at a single tertiary care center were identified. Pre- and postoperative measures were taken with the Kay Elemetrics Real-Time Pitch, Analysis of Dysphonia in Speech and Voice, and Multidimensional Voice Program. RESULTS: Twenty-eight patients were included in this study. There were no statistically significant changes in fundamental frequency variation, peak amplitude variation, soft phonation index, noise-to-harmonics ratio, cepstral peak prominence, or cepstral spectral index of dysphonia at a significance level of P < .05. Average speaking fundamental frequency (SF0) increased from 143 Hz after voice therapy to 163 Hz after surgery (P = .0009). Lower range decreased in 61% and increased in 26% of patients. Upper range decreased in 52% and increased in 48% of patients. CONCLUSIONS: Wendler glottoplasty does not worsen voice quality based on acoustic measures. Although most patients experience an increase in average SF0, effects on vocal range are variable with approximately half of patients experiencing a reduction and half experiencing an increase in upper pitch limit. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:583-586, 2021.

Addition of Wendler Glottoplasty to Voice Therapy Improves Trans Female Voice Outcomes.

OBJECTIVES/HYPOTHESIS: VT is often considered the preferred treatment for vocal feminization in transgender patients. However, Wendler glottoplasty offers a surgical option for increasing fundamental frequency and perception of vocal femininity. We aimed to determine whether the addition of glottoplasty to VT results in greater fundamental frequency elevation and improvement in quality-of-life measures. STUDY DESIGN: Retrospective case series. METHODS: Forty-eight trans female patients were treated for vocal feminization. Twenty-seven patients underwent VT, and 21 patients underwent VT with additional glottoplasty (VTWG). Pre- and posttreatment acoustic measures, Trans Woman Voice Questionnaire (TWVQ), and Voice Handicap Index-10 (VHI-10) data were compared. RESULTS: Glottoplasty in combination with VT elevated average speaking fundamental frequency (SF0) to a greater extent than VT alone (P < .0001). The VTWG group achieved a 42-Hz increase in SF0, whereas the VT group achieved a 15-Hz increase in SF0. In both the VT and VTWG groups, the lower bound of physiologic range increased by 18 Hz (P = .0008 and P = .016, respectively). The addition of glottoplasty also resulted in greater improvement in voice-related quality of life. Improvement in TWVQ and VHI-10 was significantly greater in the VTWG group than the VT group (P = .007 and P = .029, respectively). TWVQ showed statistically significant improvement in the VTWG group only. CONCLUSIONS: VT results in SF0 elevation and improvement in VHI-10. The addition of glottoplasty to VT results in further improvements in SF0 and VHI-10 and statistically significant improvement in TWVQ. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1588-1593, 2021.

Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic.

Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.

Patient Experience of Electroconvulsive Therapy: A Retrospective Review of Clinical Outcomes and Satisfaction.

OBJECTIVE: The aim of the study was to explore patient perception and perceived benefit of electroconvulsive therapy (ECT) by assessing the real-world experience of adult patients who received ECT, focusing on clinical outcomes and patient satisfaction. METHODS: This retrospective study analyzed patient self-report of depressive symptoms (Patient Health Questionnaire), perception of physical and cognitive ECT adverse effects (ECT Outcomes Survey) and satisfaction with treatment (Patient Satisfaction Survey). Symptoms and adverse effects were measured at both intake and final ECT session for comparison over time. Data were collected from 1089 adult patients with depression, bipolar disorder, or schizoaffective disorder in 23 psychiatric facilities in the United States and its territories from 2014 to 2015. RESULTS: On average, patient scores reflect satisfaction with treatment and reduction in depressive symptoms and adverse effects across the course of ECT treatment. Patients reported a decrease in depression, with an average Patient Health Questionnaire change of 13.2 from intake to final ECT session (P < 0.001). Furthermore, 85.5% of patients indicated on the Patient Satisfaction Survey that they benefited or improved as a result of their ECT. Subsequent analyses revealed alleviation of depressive symptoms and ability to return to social, and work life tasks are significant contributors to satisfaction with treatment, whereas adverse effects including memory problems have less influence on satisfaction. CONCLUSIONS: Patients tend to perceive ECT as a safe and beneficial treatment option for severe mood disorders, even when considering adverse effects. This study reinforces the value of standardized data collection and outcomes measures to better monitor patient response to treatment, refine the clinical practice of ECT, and provide data to support patient education.

Conservation implications for dingoes from the maternal and paternal genome: Multiple populations, dog introgression, and demography.

It is increasingly common for apex predators to face a multitude of complex conservation issues. In Australia, dingoes are the mainland apex predator and play an important role in ecological functioning. Currently, however, they are threatened by hybridization with modern domestic dogs in the wild. As a consequence, we explore how increasing our understanding of the evolutionary history of dingoes can inform management and conservation decisions. Previous research on whole mitochondrial genome and nuclear data from five geographical populations showed evidence of two distinct lineages of dingo. Here, we present data from a broader survey of dingoes around Australia using both mitochondrial and Y chromosome markers and investigate the timing of demographic expansions. Biogeographic data corroborate the presence of at least two geographically subdivided genetic populations, southeastern and northwestern. Demographic modeling suggests that dingoes have undergone population expansion in the last 5,000 years. It is not clear whether this stems from expansion into vacant niches after the extinction of thylacines on the mainland or indicates the arrival date of dingoes. Male dispersal is much more common than female, evidenced by more diffuse Y haplogroup distributions. There is also evidence of likely historical male biased introgression from domestic dogs into dingoes, predominately within southeastern Australia. These findings have critical practical implications for the management and conservation of dingoes in Australia; particularly a focus must be placed upon the threatened southeastern dingo population.