Perceived impact of the COVID-19 pandemic on residency training in American College of Veterinary Anesthesia and Analgesia programs in North America: a quantitative survey.

OBJECTIVE: To characterize the extent of the impact of the COVID-19 pandemic on aspects of the anesthesia residency experience from the perspective of American College of Veterinary Anesthesia and Analgesia (ACVAA) mentors and trainees. This includes the residency interview process, didactic training and availability and variety of clinical cases for resident learning. STUDY DESIGN: Cross-sectional, online, anonymous voluntary survey. SAMPLE POPULATION: A total of 58 respondents, representing 30 residency program mentors and 28 residents. METHODS: Surveys were distributed by email to 94 residency program mentors and 70 residents, representing programs and residents registered with the ACVAA during the years of 2019-2021. Anonymous links to an online survey were provided via a link embedded in the email. Questions included perceived impacts (-5 to +5 scale) on didactic and clinical training, case distribution, workload, residency application and selection process, and mental health. Responses were summarized with descriptive statistics [median (IQR) or mean ± SD]. RESULTS: The overall survey response rate was 31.9% (30/94) and 40.0% (28/70) for resident program mentors and residents, respectively. There was a negative perceived impact on overall residency training reported: -1.0 (IQR -2.0 to 0) for program mentors and -1.5 ± 1.5 for residents. The reported perceived impact of travel limitations on case log completion was -2.0 (IQR -4.0 to -1.0) for program mentors and -2.4 ± 2.0 for residents. Program mentors and residents had incongruent feelings on the impact of the pandemic on work hours, with residents reporting a perceived increase in work hours [+2.1 ± 2.1 versus 0 (IQR -1.0 to 0)]. CONCLUSIONS: Residency program mentors and residents generally agreed that the COVID-19 pandemic had negatively impacted multiple aspects of residency interview and training process. A broader, objective analysis of veterinary anesthesia training programs is required to fully elucidate the scale of the impact on veterinary anesthesia training.

Hormone-related side effects in new users of a levonorgestrel 52 mg intrauterine device.

BACKGROUND: Although the levonorgestrel 52 mg intrauterine device is locally active and has low systemic hormone exposure, hormonal intrauterine device users sometimes report hormone-related side effects. OBJECTIVE: Evaluate hormone-related adverse event rates among all participants and compare these among those who used combined hormonal or no hormonal contraception in the month before enrollment. STUDY DESIGN: A total of 1714 women aged 16-45 years old received a levonorgestrel 52 mg intrauterine device in a multicenter phase 3 trial to evaluate contraceptive efficacy and safety for up to 10 years. This analysis evaluated a subset of participants who used combined hormonal or no hormonal contraception in the month prior to device placement. We assessed all non-expulsion, non-bleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered non-hormonal. We computed 180-day side effect frequency rates based on the number of days a side effect was reported during the study period. We created a multivariable model for side effect incidence at 180 days based on age, race, ethnicity, body mass index at enrollment, parity, and contraception use in the month before enrollment. For those side effects with a p-value <0.2 on univariate comparison between combined-hormonal and no-hormonal contraception users, we secondarily evaluated 360-day event rates. RESULTS: Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before IUD placement. Individual side effect rates over the first 180 days did not differ between prior combined-hormonal and no-hormonal contraception users except for acne (84 [13.0%] versus 73 [8.5%], respectively), p=0.006, OR 1.61 (95% CI 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (aOR 1.40, 95% CI 0.99-1.98) At 360 days, prior combined hormonal contraception users were more likely to report acne (101 [15.7%] vs. 91 [10.6%], respectively, p=0.005) and orgasm/libido problems (20 [3.1%] vs. 12 [1.4%], respectively, p=0.03). Over the first 180 days, all side effects other than acne were reported in less than 3% of days; acne was reported an average of 13 days (7.4%) per prior combined hormonal contraception user and 9 days (5.0%) per prior non-hormonal contraception user (p<0.0001). Discontinuation for evaluated side effects occurred in 83 (5.5%) participants with no difference between those who used combined hormonal (36 [5.6%]) or no hormonal contraception (47 [5.5%]), p=1.0) before study entry. CONCLUSIONS: Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is only weakly associated with reporting hormonally related side effects like acne. Only a small percentage of levonorgestrel 52 mg intrauterine device users experienced potentially hormone-related side effects during the initial 6 months of use that resulted in discontinuation.

Gene protein sequence evolution can predict the rapid divergence of ovariole numbers in the Drosophila melanogaster subgroup.

Ovaries play key roles in fitness and evolution: they are essential female reproductive structures that develop and house the eggs in sexually reproducing animals. In Drosophila, the mature ovary contains multiple tubular egg-producing structures known as ovarioles. Ovarioles arise from somatic cellular structures in the larval ovary called terminal filaments, formed by terminal filament cells and subsequently enclosed by sheath cells. As in many other insects, ovariole number per female varies extensively in Drosophila. At present however, there is a striking gap of information on genetic mechanisms and evolutionary forces that shape the well-documented rapid interspecies divergence of ovariole numbers. To address this gap, here we studied genes associated with D. melanogaster ovariole number or functions based on recent experimental and transcriptional datasets from larval ovaries, including terminal filaments and sheath cells, and assessed their rates and patterns of molecular evolution in five closely related species of the melanogaster subgroup that exhibit species-specific differences in ovariole numbers. From comprehensive analyses of protein sequence evolution (dN/dS), branch-site positive selection, expression specificity (tau) and phylogenetic regressions (PGLS), we report evidence of 42 genes that showed signs of playing roles in the genetic basis of interspecies evolutionary change of Drosophila ovariole number. These included the signalling genes upd2 and Ilp5 and extracellular matrix genes vkg and Col4a1, whose dN/dS predicted ovariole numbers among species. Together, we propose a model whereby a set of ovariole-involved gene proteins have an enhanced evolvability, including adaptive evolution, facilitating rapid shifts in ovariole number among Drosophila species.

The LTAR Common Experiment at Upper Chesapeake Bay: Integrated.

Corn (Zea mays) crops harvested as grain in autumn do not provide opportunity for cover crop establishment, which may be remedied by interseeding cover crops into growing corn. Grazing cover crops after corn grain harvest could provide added revenues and increase nutrient cycling in the system while providing additional ecosystem services. However, tradeoffs between cash crop productivity and cover crop inclusion, and use as grazed forage, are not fully understood. This 4-year Long-Term Agroecosystem Research Integrated Common Experiment project evaluated the effect of interseeding cereal rye (Secale cereale) into corn for grazing after corn grain harvest on corn grain yield and late-season grazing. Cereal rye was interseeded into corn in early June. After corn grain harvest, six paddocks at each location were randomly allotted to grazed (GRAZ) or not grazed (NG). The GRAZ paddocks were grazed with beef cattle in late autumn and again in early spring if regrowth allowed. Paddocks were flown with an unmanned aerial system (UAS) to characterize spatial forage yield and quality. Cereal rye provided an additional 20-30 grazing days in the autumn for 24 beef cows on 4.8 ha. Early spring growth shows potential to provide even greater forage yields than autumn, but growth is less dependable. Corn grain yields did not decrease except in 2019 (dry year) when yields were 40% lower. There were no significant differences in soil health indicators between GRAZ and NG paddocks. The UAS shows promise as a tool for monitoring forage yield and quality and optimizing grazing management.

Exploring Climate-Disease Connections in Geopolitical Versus Ecological Regions: The Case of West Nile Virus in the United States.

Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to regions defined by natural ecosystems; although useful for data collection and intervention, this has the potential to mask biological relationships between the environment and disease. We explored this concept by analyzing the correlations between climate and West Nile virus (WNV) case data aggregated to geopolitical and ecological regions. We compared correlations between minimum, maximum, and mean annual temperature; precipitation; and annual WNV neuroinvasive disease (WNND) case data from 2005 to 2019 when partitioned into (a) climate regions defined by the National Oceanic and Atmospheric Administration (NOAA) and (b) Level I ecoregions defined by the Environmental Protection Agency (EPA). We found that correlations between climate and WNND in NOAA climate regions and EPA ecoregions were often contradictory in both direction and magnitude, with EPA ecoregions more often supporting previously established biological hypotheses and environmental dynamics underlying vector-borne disease transmission. Using ecological regions to examine the relationships between climate and disease cases can enhance the predictive power of forecasts at various scales, motivating a conceptual shift in large-scale analyses from geopolitical frameworks to more ecologically meaningful regions.

Impact of Primary Letermovir Prophylaxis Versus Preemptive Antiviral Therapy for Cytomegalovirus on Economic and Clinical Outcomes after Hematopoietic Cell Transplantation.

Preemptive therapy (PET) historically has been the primary strategy to reduce early-onset cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplantation (HCT) but is associated with antiviral-associated toxicities and increases in healthcare resource utilization and cost. Despite its high cost, letermovir (LTV) prophylaxis has largely supplanted PET due to its effectiveness and tolerability. Direct comparisons between LTV and PET approaches on economic and clinical outcomes after allogeneic HCT remain limited. Objective: To compare total cost of care (inpatient and outpatient) between LTV prophylaxis and PET through day+180 after allogeneic HCT. Adult allogeneic CMV seropositive (R+) HCT recipients who initiated LTV <30 days after HCT between 01/01/18 and 12/31/18 were matched 1:1 to allogeneic CMV R+ HCT recipients between 01/01/15 and 12/31/17 (PET cohort). Patients were grouped into high-risk (HR) or standard-risk (SR) for CMV to compare the LTV and PET cohorts. Direct costs for each patient's index HCT admission and all subsequent inpatient and outpatient care through day+180 after HCT were determined and converted into 2021 US dollars and then to Medicare proportional dollars (MPD). A secondary analysis using 2019 average wholesale price was conducted to specifically evaluate anti-CMV medication costs. There were a total of 176 patients with 54 HR CMV pairs and 34 SR CMV pairs. No differences in survival between LTV and PET for both HR and SR CMV groups were observed. The rate of clinically significant CMV infection decreased for both HR CMV (11/54, 20.4% versus 38/54, 70.4%, P < .001) and SR CMV (1/34, 2.9% versus 12/34, 35.3%, P < .001) patients who were given LTV prophylaxis with corresponding reductions in val(ganciclovir) and foscarnet (HR CMV only) use. Among HR CMV patients, LTV prophylaxis was associated with reductions in CMV-related readmissions (3/54, 5.6% versus 18/54, 33.3%, P < .001) and outpatient visits within the first 100 days after HCT (20 versus 25, P = .002), and a decreased median total cost of care ($36,018 versus $75,525, P < .001) in MPD was observed. For SR CMV patients on LTV, a significant reduction in the median inpatient cost ($15,668 versus $27,818, P < .001) was found, but this finding was offset by a higher median outpatient cost ($26,145 versus $20,307, P = .030) that was not CMV-driven. LTV prophylaxis is highly effective in reducing clinically significant CMV reactivations for both HR and SR HCT recipients. In this study, LTV prophylaxis was associated with a decreased total cost of care for HR CMV patients through day+180. Specifically, reductions in CMV-related readmissions, exposure to CMV-directed antiviral agents, and outpatient visits in the first 100 days after HCT were observed. SR CMV patients receiving LTV prophylaxis benefited by having a reduced inpatient cost of care due to lowered room and pharmacy costs.

Case report: Chylopericardium secondary to dialysis catheter related jugular venous thrombosis in two dogs receiving long-term hemodialysis.

Chylopericardium is a rare entity in veterinary medicine. In this report we document the development of chylopericardium in two dogs undergoing chronic hemodialysis. An 11-year-old female spayed Labrador retriever (Case 1) presented with acute coughing and lethargy 2 months following initial dialysis catheter placement and initiation of dialysis therapy for severe azotemia. Echocardiography demonstrated severe pericardial effusion and cardiac tamponade. Pericardial fluid analysis was consistent with chylous effusion. The dog underwent a subtotal pericardiectomy with thoracic duct ligation, and a PleuralPort™ was placed. The patient continued to receive outpatient hemodialysis therapy after pericardiectomy for several months until she died acutely at home. A 4-year-old male neutered Doberman (Case 2) was being treated for 2 months with outpatient hemodialysis for management of chronic kidney disease. On presentation for the 17th hemodialysis treatment, the patient had increased respiratory rate. Echocardiography demonstrated pleural and pericardial effusions, and fluid analysis in both cavities was consistent with chylous effusion. Use of tissue plasminogen activator (TPA), clot removal and replacement of the catheter was attempted; however pleural and pericardial effusion continued. The patient was euthanized after 25 hemodialysis sessions as owners elected not to pursue more procedures. In both cases, the cause of the chylopericardium was suspected to be secondary to catheter-associated thrombosis and/or stenosis based on multiple imaging modalities. Despite use of rivaroxaban and clopidogrel concurrently in each case, the chylous effusion persisted. This case report describes clinical details of a rare complication of long-term indwelling dialysis catheters in two dogs.

Human exposure to per- and polyfluoroalkyl substances (PFAS) via the consumption of fish leads to exceedance of safety thresholds.

Per- and polyfluoroalkyl substances (PFAS) receive global attention due to their adverse effects on human health and the environment. Fish consumption is a major source of human PFAS exposure. The aim of this work was to address the lack of harmonization within legislations (in the EU and the USA) and highlight the level of PFAS in fish exposed to pollution from diffuse sources in the context of current safety thresholds. A non-exhaustive literature review was carried out to obtain PFAS concentrations in wild fish from the Norwegian mainland, Svalbard, the Netherlands, the USA, as well as sea regions (North Sea, English Channel, Atlantic Ocean), and farmed fish on the Dutch market. Median sum wet weight concentrations of PFOA, PFNA, PFHxS, and PFOS ranged between 0.1 µg kg-1 (farmed fish) and 22 µg kg-1 (Netherlands eel). Most concentrations fell below the EU environmental quality standard (EQSbiota) for PFOS (9.1 µg kg-1) and would not be defined as polluted in the EU. However, using recent tolerable intake or reference dose values in the EU and the USA revealed that even limited fish consumption would lead to exceedance of these thresholds - possibly posing a challenge for risk communication.

N-glucuronidation and Excretion of Perfluoroalkyl Sulfonamides in Mice Following Ingestion of Aqueous Film-Forming Foam.

Perfluoroalkyl sulfonamides (FASAs) and other FASA-based per- and polyfluoroalkyl substances (PFASs) can transform into recalcitrant perfluoroalkyl sulfonates in vivo. We conducted high-resolution mass spectrometry suspect screening of urine and tissues (kidney and liver) from mice dosed with an electrochemically fluorinated aqueous film-forming foam (AFFF) to better understand the biological fate of AFFF-associated precursors. The B6C3F1 mice were dosed at five levels (0, 0.05, 0.5, 1, and 5 mg kg-1 day-1) based on perfluorooctane sulfonate and perfluorooctanoate content of the AFFF mixture. Dosing continued for 10 days followed by a 6-day depuration. Total oxidizable precursor assay of the AFFF suggested significant contributions from precursors with three to six perfluorinated carbons. We identified C4 to C6 FASAs and N-glucuronidated FASAs (FASA-N-glus) excreted in urine collected throughout dosing and depuration. Based on normalized relative abundance, FASA-N-glus accounted for up to 33% of the total excreted FASAs in mouse urine, highlighting the importance of phase II metabolic conjugation as a route of excretion. High-resolution mass spectrometry screening of liver and kidney tissue revealed accumulation of longer-chain (C7 and C8) FASAs not detected in urine. Chain-length-dependent conjugation of FASAs was also observed by incubating FASAs with mouse liver S9 fractions. Shorter-chain (C4) FASAs conjugated to a much greater extent over a 120-min incubation than longer-chain (C8) FASAs. Overall, this study highlights the significance of N-glucuronidation as an excretion mechanism for short-chain FASAs and suggests that monitoring urine for FASA-N-glus could contribute to a better understanding of PFAS exposure, as FASAs and their conjugates are often overlooked by traditional biomonitoring studies. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Application of functional genomics for domestication of novel non-model microbes.

With the expansion of domesticated microbes producing biomaterials and chemicals to support a growing circular bioeconomy, the variety of waste and sustainable substrates that can support microbial growth and production will also continue to expand. The diversity of these microbes also requires a range of compatible genetic tools to engineer improved robustness and economic viability. As we still do not fully understand the function of many genes in even highly studied model microbes, engineering improved microbial performance requires introducing genome-scale genetic modifications followed by screening or selecting mutants that enhance growth under prohibitive conditions encountered during production. These approaches include adaptive laboratory evolution, random or directed mutagenesis, transposon-mediated gene disruption, or CRISPR interference (CRISPRi). Although any of these approaches may be applicable for identifying engineering targets, here we focus on using CRISPRi to reduce the time required to engineer more robust microbes for industrial applications. ONE-SENTENCE SUMMARY: The development of genome scale CRISPR-based libraries in new microbes enables discovery of genetic factors linked to desired traits for engineering more robust microbial systems.

Cultured Skin in the Modern Era and the Impact of Infrastructure Volatility on Learning Curves: A 33-Year Institutional Review.

Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use of CEA for the treatment of major burns was first reported in 1981. CEA requires specialized skills; thus, reports from different burn-centers have shown mixed results. Comparing our modern data with past data shows how this field has advanced while maintaining institutional control. We performed a retrospective analysis of all patients admitted between 01/01/1988-12/31/2021 for massive burns that were managed with CEA. Patients were divided into pre-defined groups: G1(early-era)=1988-1999, G2(pre-modern-era)=2000-2010, and G3(modern-era)=2011-2021. We compared demographics, %TBSA, presence of inhalation-injury, LOS, complications, and mortality. We treated 52 patients with CEA during the study period. In the modern-era, we found 11 patients; in the pre-modern-era, 10; and in the early-era, 31. Injury characteristics, including %TBSA and the presence of inhalation-injury, were not significantly different between the groups. We observed lower mortality rates in G1 and G3 (G1:20% vs. G2:42% vs. G3:27%, p<0.05), although the predicted mortality was not significantly different between the groups (G1:50% vs. G2:47% vs. G3:49%, NS). Patients in G1 also had a shorter hospital LOS, in days, (G1:90 vs. G2:127 vs. G3:205, p<0.05). Finally, the surface-area grafted per patient was the highest in G2 (G1:2,000cm2 vs. G2:4,187cm2 vs. G3:4,090cm2, p<0.01). CEA has not gained popularity despite proven positive outcomes. Our retrospective analysis showed that CEA should be considered as a treatment option for patients with large burns, given proper training and infrastructure.

Insights into Electrochemical CO2 Reduction on Metallic and Oxidized Tin Using Grand-Canonical DFT and In Situ ATR-SEIRA Spectroscopy.

Electrochemical CO2 reduction (CO2R) to formate is an attractive carbon emissions mitigation strategy due to the existing market and attractive price for formic acid. Tin is an effective electrocatalyst for CO2R to formate, but the underlying reaction mechanism and whether the active phase of tin is metallic or oxidized during reduction is openly debated. In this report, we used grand-canonical density functional theory and attenuated total reflection surface-enhanced infrared absorption spectroscopy to identify differences in the vibrational signatures of surface species during CO2R on fully metallic and oxidized tin surfaces. Our results show that CO2R is feasible on both metallic and oxidized tin. We propose that the key difference between each surface termination is that CO2R catalyzed by metallic tin surfaces is limited by the electrochemical activation of CO2, whereas CO2R catalyzed by oxidized tin surfaces is limited by the slow reductive desorption of formate. While the exact degree of oxidation of tin surfaces during CO2R is unlikely to be either fully metallic or fully oxidized, this study highlights the limiting behavior of these two surfaces and lays out the key features of each that our results predict will promote rapid CO2R catalysis. Additionally, we highlight the power of integrating high-fidelity quantum mechanical modeling and spectroscopic measurements to elucidate intricate electrocatalytic reaction pathways.

Emergency Department Visits for Mild Traumatic Brain Injury: Associations with Geriatric Age, Sex, and Fall Injury.

PURPOSE: The highest rates mTBI occurrence are seen among geriatric populations (ages ≥65), and these patients often have persistent and untreated symptoms. This study's purpose was to explore mild traumatic brain injury initial onset (mTBI-IN) and mild traumatic brain injury subsequent (mTBI-S) emergency department (ED) visit population percentages and associations with geriatric (population ages ≥65), sex, and fall mechanism of injury. METHODS: The design was a population-based cross-sectional study using data from the 2018 Nationwide Emergency Department Sample (NEDS). Study sample size was 261,349. An independent t-test was used to investigate mean age differences between mTBI-IN and mTBI-S. Pearson's chi-squared correlational analyses were used to investigate associations of age, sex, and fall injury with mTBI-IN and mTBI-S. RESULTS: The mean age of those in 2018 with ED visits suggested that age was older for those patients with mTBI-S (age mean, 50.4 yrs) than those with mTBI-IN (age mean, 41.4 yrs) (95% CI 9.77, 8.30; p=0.025). The number of visits for those aged ≥65 was significantly associated with mTBI-S (p<0.001). More males than females reported mTBI-S ED visits in all ages (p=0.022). Falls injury alone was not found to be significantly associated with visits (p<0.001). CONCLUSIONS: Those returning to the ED for continued care after mTBI were associated with those aged ≥65. Monitoring after mTBI ED visits may need to target geriatric populations for medical management.

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

BACKGROUND AND OBJECTIVES: Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. RESULTS: The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. DISCUSSION: Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. TRIAL REGISTRATION INFORMATION: The study is registered at ClinicalTrials.gov as NCT01730170.

Device and Fitting Protocol for a Transitional Intervention for Debilitating Hyperacusis.

PURPOSE: This report describes a hearing device and corresponding fitting protocol designed for use in a transitional intervention for debilitating loudness-based hyperacusis. METHOD: The intervention goal is to transition patients with hyperacusis from their typical counterproductive sound avoidance behaviors (i.e., sound attenuation and limited exposure to healthy low-level sounds) into beneficial sound therapy treatment that can expand their dynamic range to the point where they can tolerate everyday sounds and experience an improved quality of life. This requires a combination of counseling and sound therapy, the latter of which is provided via the hearing device technology, signal processing, and precision fitting approach described in this report. The device combines a miniature behind-the-ear sound processor and a custom earpiece designed to maximize the attenuation of external sounds. Output-limiting loudness suppression is used to restrict exposure to offending high-level sounds while unity gain amplification maximizes exposure to healthy and tolerable lower level sounds. The fitting process includes measurement of the real-ear unaided response, the real-ear measurement (REM) system noise floor, the real-ear occluded response, real-ear insertion gain, and the output limit. With these measurements, the device can achieve the prescribed unity gain needed to provide transparent access to comfortable sound levels. It also supports individualized configuration of the therapeutic noise from an on-board sound generator and adaptive output limiting based on treatment-induced increases in dynamic range. RESULTS AND CONCLUSION: The utility of this device and fitting protocol, in combination with structured counseling, is highlighted in the outcomes of a successful 6-month trial of the transitional intervention described in a companion report in this issue.

Results of a 6-Month Field Trial of a Transitional Intervention for Debilitating Hyperacusis.

PURPOSE: We present results from a 6-month field trial of a transitional intervention for debilitating primary hyperacusis, including a combination of structured counseling; promotion of safe, comfortable, and healthy sound exposure; and therapeutic broadband sound from sound generators. This intervention is designed to overcome barriers to successful delivery of therapeutic sound as a tool to downregulate neural hyperactivity in the central auditory pathways (i.e., the maladaptive mechanism believed to account for primary hyperacusis) and, together with the counseling, reduce the associated negative emotional and physiological reactions to debilitating hyperacusis. METHOD: Twelve adults with normal or near-normal audiometric thresholds, complaints consistent with their pretreatment loudness discomfort levels ≤ 75 dB HL at multiple frequencies, and hearing questionnaire scores ≥ 24 completed the sound therapy-based intervention. The low-level broadband therapeutic sound was delivered by ear-level devices fitted bilaterally with either occluding earpieces and output-limiting loudness suppression (LS; to limit exposure to offensive sound levels) or open domes to maximize comfort and exposure to sound therapy. Thresholds for LS (primary outcome) were incrementally adjusted across six monthly visits based on treatment-driven change in loudness judgments for running speech in sound field. Secondary outcomes included categorical loudness judgments, speech understanding, and questionnaires to assess the hyperacusis problem, quality of life, and depression. An exit survey assessed satisfaction with and benefit from the intervention and the counseling, therapeutic sound, and LS components. RESULTS: The mean change in LS (34.8 dB) was highly significant (effect size = 2.045). Eleven of 12 participants achieved ≥ 16-dB change in LS, consistent with highly significant change in sound-based questionnaire scores. Exit surveys indicated satisfaction with and benefit from the intervention. CONCLUSION: The transitional intervention was successful in improving the hyperacusis conditions of 11 of 12 study participants while reducing their sound avoidance behaviors and reliance on sound protection.

Counseling Protocol for a Transitional Intervention for Debilitating Hyperacusis.

INTRODUCTION: This clinical focus article describes a structured counseling protocol for use with protected sound management and therapeutic sound in a transitional intervention for debilitating hyperacusis. The counseling protocol and its associated visual aids are crafted as a teaching tool to educate affected individuals about hyperacusis and encourage their acceptance of a transitional intervention. DESCRIPTION OF COUNSELING COMPONENTS: The counseling protocol includes five components. First, the patient's audiometric results are reviewed with the patient, and the transitional intervention is introduced. An overview of peripheral auditory structures and central neural pathways and the concept of central gain are covered in the second and third components. Maladaptive hyper-gain processes within the auditory neural pathways, which underlie the hyperacusis condition, and associated connections with nonauditory processes responsible for negative reactions to hyperacusis are covered in the fourth component. Detrimental effects from misused hearing protection devices (HPDs) and the necessity to wean the patient from overuse of HPDs are also discussed. In the fifth component, the importance of therapeutic sound is introduced as a tool to downregulate hyper-gain activity within the auditory pathways; its implementation in uncontrolled and controlled sound environments is described. It is explained that, over the course of the transitional intervention, recalibration of the hyper-gain processes will be ongoing, leading to restoration of normal homeostasis within the auditory pathways. In turn, associated activation of reactive nonauditory processes, which contribute to hyperacusis-related distress, will be reduced or eliminated. As recalibration progresses, there will be less need for protected sound management and sound therapy. Sound tolerance will improve, hyperacusis will subside, and daily activities in typical healthy sound environments will again become routine. RESULTS AND CONCLUSION: The combination of counseling with protected sound management and therapeutic sound is highlighted in companion reports, including a summary of the outcomes of a successful trial of the transitional intervention.

Background and Rationale for a Transitional Intervention for Debilitating Hyperacusis.

PURPOSE: This report provides the experimental, clinical, theoretical, and historical background that motivated a patented transitional intervention and its implementation and evaluation in a field trial for mitigation of debilitating loudness-based hyperacusis (LH). BACKGROUND AND RATIONALE: Barriers for ameliorating LH, which is differentiated here from other forms of hyperacusis, are delineated, including counterproductive management and treatment strategies that may exacerbate the condition. Evidence for hyper-gain central auditory processes as the bases for LH and the associated LH-induced distress and stress responses are presented. This presentation is followed by an overview of prior efforts to use counseling and therapeutic sound as interventional tools for recalibrating the hyper-gain LH response. We also consider previous efforts to use output-limiting sound-protection devices in the management of LH. This historical background lays the foundation for our transitional intervention protocol and its implementation and evaluation in a field trial. CONCLUSIONS: The successful implementation and evaluation of a transitional intervention, which we document in the outcomes of a companion proof-of-concept field trial in this issue, build on our prior efforts and those of others to understand, manage, and treat hyperacusis. These efforts to overcome significant barriers and vexing long-standing challenges in the management and treatment of LH, as reviewed here, are the pillars of the transitional intervention and its primary components, namely, counseling combined with protective sound management and therapeutic sound, which we detail in separate reports in this issue.