Exacerbations, treatment patterns, utilization, and costs before and after initiating of benralizumab for the treatment of severe eosinophilic asthma.

OBJECTIVES: The purpose of this study was to examine the number of exacerbations, counts of eosinophils, and asthma-related symptoms 1 year before and after initiating benralizumab for the treatment of severe eosinophilic asthma. METHODS: Patients with prior exacerbations and newly initiating benralizumab were identified in the claims-based Healthcare Integrated Research Database. Claims were used to assess benralizumab treatment patterns, exacerbations, healthcare resource utilization, and other asthma medication used. Among a subset of patients, medical records were abstracted for Asthma Control Test (ACT) scores and asthma symptoms. RESULTS: There were 506 patients meeting inclusion/exclusion criteria for claims-based analyses and 123 for medical-record analyses. The number of patients experiencing exacerbations significantly decreased from baseline to follow-up (40% reduction, McNemar's χ2 = 204.00, p < .001). The mean number of exacerbations also decreased from 3.2 (1.5) to 1.2 (1.4) (paired t = 24.45, p < .001; Cohen's D = 1.09). The effects were larger among patients with eosinophils ≥300 cells/µL. Among patients with an ACT available for baseline and follow-up (n = 47), there was a significant reduction in the number of patients with scores <19 (72% vs. 45%, p < .01). CONCLUSIONS: Treatment with benralizumab resulted in fewer exacerbations, reduced utilization, and improved ACT scores. This study demonstrates that benralizumab is an effective treatment option for patients with severe eosinophilic asthma.

Building an Integrated Data Infrastructure to Examine the Spectrum of Suicide Risk Factors in Philadelphia Medicaid.

While there are many data-driven approaches to identifying individuals at risk of suicide, they tend to focus on clinical risk factors, such as previous psychiatric hospitalizations, and rarely include risk factors that occur in nonclinical settings, such as jails or emergency shelters. A better understanding of system-level encounters by individuals at risk of suicide could help inform suicide prevention efforts. In Philadelphia, we built a community-level data infrastructure that encompassed suicide death records, behavioral health claims, incarceration episodes, emergency housing episodes, and involuntary commitment petitions to examine a broader spectrum of suicide risk factors. Here, we describe the development of the data infrastructure, present key trends in suicide deaths in Philadelphia, and, for the Medicaid-eligible population, determine whether suicide decedents were more likely to interact with the behavioral health, carceral, and housing service systems compared to Medicaid-eligible Philadelphians who did not die by suicide. Between 2003 and 2018, there was an increase in the number of annual suicide deaths among Medicaid-eligible individuals, in part due to changes in Medicaid eligibility. There were disproportionately more suicide deaths among Black and Hispanic individuals who were Medicaid-eligible, who were younger on average, compared to suicide decedents who were never Medicaid-eligible. However, when we accounted for the racial and ethnic composition of the Medicaid population at large, we found that White individuals were four times as likely to die by suicide, while Asian, Black, Hispanic, and individuals of other races were less likely to die by suicide. Overall, 58% of individuals who were Medicaid-eligible and died by suicide had at least one Medicaid-funded behavioral health claim, 10% had at least one emergency housing episode, 25% had at least one incarceration episode, and 22% had at least one involuntary commitment. By developing a data infrastructure that can incorporate a broader spectrum of risk factors for suicide, we demonstrate how communities can harness administrative data to inform suicide prevention efforts. Our findings point to the need for suicide prevention in nonclinical settings such as jails and emergency shelters, and demonstrate important trends in suicide deaths in the Medicaid population.

Medication use among patients with Crohn's disease or ulcerative colitis before and after the initiation of advanced therapy.

BACKGROUND: Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC. METHODS: This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test. RESULTS: Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC). CONCLUSIONS: The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.

Falls from Tree Stands Have Become the Leading Cause of Deer Hunting Accidents in Pennsylvania.

OBJECTIVES: This study aimed to describe, using a statewide trauma registry, the incidence, trends, and injuries for tree stand falls while deer hunting in Pennsylvania. METHODS: Falls from tree stands were abstracted from the Pennsylvania Trauma Systems Foundation registry (1990-2017) and combined with the number of licensed deer hunters, deer hunting days, and deer hunting-related shooting incidents (HRSIs) provided by the Pennsylvania Game Commission to calculate tree stand fall and HRSI rates (per 1 million deer hunting days) and age-group specific fall rates (per 100,000 licensed deer hunters). Poisson regression was used to assess the significance of the annual and age group rate trends (significance P < 0.05). Case fatality rate (percentage of number of deaths per number of injured hunters) also was calculated. RESULTS: There were 1229 victims of tree stand falls and 560 victims of HRSIs between 1990 and 2017. Fall rates increased from 1.5 to 10.4 (P < 0.0001), and HRSI rates decreased from 4.9 to 1.2 (P = 0.001). Fall rates surpassed HRSI rates in 1999 and increased with advancing age (P = 0.007), peaking at 7.2 for hunters aged 50 to 59 years. Most (77%) injured hunters sustained multiple injuries. The case fatality rate was only 0.8%, but 26% of the injured hunters had a dependent functional limitation at hospital discharge. CONCLUSIONS: Tree stand falls are now the leading cause of Pennsylvania deer hunting accidents. Fall victims usually sustain multiple nonfatal but often disabling injuries. Study findings support the need for surveillance of these accidents and additional tree stand safety education.

Association of Dulaglutide Initiation Timing With Treatment Patterns and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus in the United States.

PURPOSE: To describe clinical characteristics and treatment outcomes for early or late initiation of dulaglutide therapy in patients with type 2 diabetes. METHODS: This retrospective, claims-based analysis evaluated adults with type 2 diabetes, ≥1 claim for dulaglutide 0.75 mg or 1.5 mg once-weekly injection (between November 2014 and August 2019), and no prior use of glucagon-like peptide 1 receptor agonists or insulin. Cohorts were defined based on the number of oral antidiabetic drug (OAD) classes used within the 24-month baseline period before dulaglutide therapy initiation: 1 OAD, 2 OADs, or ≥3 OADs. The number of OAD classes used before dulaglutide therapy initiation served as a proxy for timing of initiation, with a higher number of OAD classes indicating a longer duration of T2D. Baseline demographic and clinical characteristics were compared across each cohort. Six-month follow-up outcomes, including change in glycosylated hemoglobin (HbA1c) and treatment patterns, were descriptively assessed within each cohort. FINDINGS: The study population consisted of 18,121 patients across the 1 OAD (n = 4822), 2 OADs (n = 6293), and ≥3 OADs (n = 7006) cohorts. Mean age at baseline was 54.7 years. Males were more prevalent in the ≥3 OADs cohort. Most patients (67%-70%) initiated treatment with dulaglutide 0.75 mg. Dose escalation to 1.5 mg was uncommon (15%-20%) but trended higher in the ≥3 OAD cohort. Adherence to dulaglutide at 6-month follow-up (61%-67%) increased with higher baseline OAD use. The HbA1c assessment (n = 3178) included 761 patients in the 1 OAD cohort, 1088 patients in the 2 OADs cohort, and 1329 patients in the ≥3 OADs cohort. Baseline mean [SD] HbA1c level increased with number of OAD classes (1 OAD: 8.18% [1.80]; 2 OADs: 8.56% [1.66]; and ≥3 OADs: 8.73% [1.51]). Patients in the early dulaglutide therapy initiator group experienced larger reductions in HbA1c levels (1 OAD: -1.39%; 95% CI, -1.50 to -1.27; 2 OADs: -1.30%; 95% CI, -1.39 to -1.20; and ≥3 OADs: -1.01%; 95% CI, -1.09 to -0.93) versus the patients in the delayed initiator group. Patients in the early dulaglutide therapy initiator group also achieved HbA1c <7% at 6-month follow-up more frequently than those in the later initiator group (1 OAD: 68%; 2 OADs: 51%; and ≥3 OADs: 33%). IMPLICATIONS: Cohorts of dulaglutide therapy initiators, defined by prior OAD use as a proxy of timing of initiation, differed in their baseline characteristics and short-term follow-up outcomes. Earlier dulaglutide therapy initiation was associated with lower mean HbA1c levels and increased probability of achievement of HbA1c <7% during the 6-month follow-up period.

Behavioral health service use post-jail release and reduced risk of return to jail.

This study examined whether behavioral health service use post-jail release was associated with reduced risk of jail reincarceration. The study sample included 20,615 individuals who had behavioral health diagnoses and were released from the Philadelphia County jail. Using administrative records of the county jail and state-, county-, and Medicaid-funded behavioral health service use from 2010 to 2018, we conducted Cox proportional hazard analyses to estimate the association between behavioral health service use post-jail release and the risk of return to jail within 3 years. Nearly 50% of the sample returned to jail within 3 years. Individuals who used behavioral health services were 26%-38% less likely to return to jail within 3 years than were individuals who did not. The study results suggest that connecting individuals with behavioral health services upon release from jail can reduce the risk of repeated jail incarceration.

Item-specific encoding reduces false recognition of homograph and implicit mediated critical lures.

We evaluated the effects of item-specific and relational encoding instructions on false recognition for critical lures that originated from homograph and mediated study lists. Homograph lists contained list items that were taken from two meanings of the same critical lure (e.g., autumn, trip, harvest, stumble; for fall) which disrupted thematic/gist consistency of the list. Mediated lists contained unrelated list items (e.g., slippery, spicy, vent, sleigh) that were indirectly related to a critical lure (e.g., cold), through a set of non-presented mediators (e.g., wet, hot, air, snow), and had no thematic/gist consistency. In two experiments, item-specific and relational encoding improved correct recognition relative to a read-only control task, but only item-specific encoding reduced false recognition of critical lures. Signal-detection analyses indicated that the item-specific reduction increased test-based monitoring. The item-specific reduction for homograph and mediated critical lures is consistent with the activation-monitoring framework given gist-based processes are reduced or eliminated on these list types.

Trends in antipsychotic prescribing for approved and unapproved indications to Medicaid-enrolled youth in Philadelphia, Pennsylvania between 2014 and 2018.

BACKGROUND: Antipsychotic prescribing to Medicaid-enrolled youth has been the target of numerous policy initiatives, including prior authorization and quality monitoring programs, which often target specific populations. Whether these efforts have changed the level or composition of antipsychotic prescribing is unclear. METHODS: Using 2014-2018 administrative claims data for Medicaid enrollees aged 21 years and under in Philadelphia, Pennsylvania, we measured antipsychotic prescription fills overall and for youth without an approved indication (autism, bipolar disorder, or psychosis). We then assessed whether trends differed for populations that have been targeted by policy initiatives, including younger children and foster care-enrolled youth. We also identified the most common approved and unapproved indications and examined whether the treatment duration of antipsychotic prescriptions differed based on whether the youth had an approved or unapproved indication. RESULTS: Overall, the number of Medicaid youth with an antipsychotic prescription fill halved between 2014 and 2018. Youth aged 17 years and under and foster care-enrolled youth, who were targeted by prior authorization and quality improvement efforts, experienced larger declines. Roughly half of prescriptions were for unapproved indications in both 2014 and 2018; the most common unapproved indication was ADHD, and the treatment duration was shorter for unapproved indications compared to approved indications. CONCLUSIONS: Antipsychotic prescribing to Medicaid-enrolled youth is declining, particularly among populations that have been targeted by policy initiatives like prior authorization and quality monitoring programs. Despite the fact that these initiatives often assess diagnostic criteria, half of antipsychotic prescriptions were for unapproved indications in both 2014 and 2018. More research is needed to gauge whether this prescribing is appropriate.

The Changing Landscape of Community Mental Health Care: Availability of Treatment Services in National Data, 2010-2017.

OBJECTIVE: The authors sought to describe changes in availability of crisis and substance use treatment services in U.S. mental health facilities (including outpatient and inpatient facilities) from 2010 to 2017. METHODS: Using National Mental Health Services Survey data, the authors of this descriptive study examined changes in the proportion of facilities providing crisis and substance use treatment services during the 2010-2017 period. RESULTS: Although the proportion of outpatient facilities offering treatment for substance use increased significantly during the period studied (adjusted relative risk [ARR]=1.05, 95% confidence interval [CI]=1.01-1.10), the proportion of outpatient facilities offering crisis services significantly decreased, including emergency psychiatric walk-in services (ARR=0.81, 95% CI=0.75-0.88) and crisis intervention (ARR=0.88, 95% CI=0.83-0.93). CONCLUSIONS: Mental health facilities are an integral piece of the behavioral health safety net and need to respond to changes in service needs. Findings suggest that mental health facilities have not shifted their services mix to address the ongoing suicide epidemic.

Factors Associated With Length of Stay in Emergency Departments for Pediatric Patients With Psychiatric Problems.

OBJECTIVES: Length of stay (LOS) and boarding for pediatric psychiatric patients presenting in the emergency department (ED) have been understudied, despite evidence that children with psychiatric disorders experience longer LOS relative to those without. This investigation examined correlates of LOS and boarding among youth with psychiatric disorders presenting to the ED in a large, statewide database. METHODS: Using the 2010 to 2013 Florida ED discharge database, generalized linear mixed models were used to examine for associations between LOS and patient and hospital characteristics among pediatric patients (<18 years) who presented with a primary psychiatric diagnosis (N = 44,328). RESULTS: Patients had an overall mean ± SD ED LOS of 5.96 ± 8.64 hours. Depending on the definition used (ie, 12 or 6 hours), between 23% and 58% of transferred patients were boarded. Patient characteristics associated with a longer LOS included female sex, being 15 to 17 years old, Hispanic ethnicity, having Medicaid or VA/TriCare insurance, having impulse control problems, having mood or psychotic disorders, and exhibiting self-harm behaviors. Patient transfer, large hospital size, and rural designation were associated with longer LOS. Teaching hospital status and profit status were not significantly associated with LOS. CONCLUSIONS: These data suggest that LOS for pediatric psychiatry patients in the ED varies significantly by psychiatric presentation, patient disposition, and hospital factors. Such findings have implications for quality of care, patient safety, and health outcomes.

Outpatient Treatment Patterns of Pediatric Obsessive-Compulsive Disorder.

INTRODUCTION: Little is known about community physician treatment practices for children with obsessive-compulsive disorder (OCD). This study is the first to describe the treatment of pediatric OCD in office-based and outpatient department-based physicians in the United States. METHODS: Data from the 2003-2011 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were used. We provided descriptive statistics for sample characteristics and treatments administered during the visit, and examined differences in treatment by comorbid conditions and settings using logistic regression. RESULTS: Psychotherapy was provided in 46% of visits in children with OCD overall, while serotonin reuptake inhibitor (SRI) medication was prescribed to 55% overall, atypical antipsychotics were prescribed to 22% of youth either alone or in combination with another medication; 11% received no psychotherapy or pharmacotherapy. Psychotherapy and at least one pharmacotherapy were provided to 36% of patients. There were no significant differences in characteristics of patients receiving each class of medication. CONCLUSION: Among children and adolescents, OCD was primarily treated by physicians using SRI medication and/or psychotherapy. A sizeable proportion of children were given atypical antipsychotic medications. Wider dissemination of evidence-based psychological treatments and continued monitoring of adherence to guidelines is warranted.

Outpatient Treatment of Tic Disorders Among Children and Adults.

INTRODUCTION: Limited information is available regarding treatment practices in applied settings for children and adults with tic disorders (TDs). We describe, for the first time, the treatment of TDs in U.S. children and adults in the outpatient setting. METHODS: Data from the 2003-2010 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Care Survey were used. Descriptive statistics for modality of treatment and class of pharmacological medications were reported by patient and visit characteristics. Separate multivariable logistic regression models were used to examine associations between patient and visit characteristics and classes of medications prescribed. RESULTS: One third (n = 99) of the sample did not receive any psychiatric or psychological treatment. Nearly two-thirds received a psychotropic medication. The most common class of medication was alpha-2 agonists (25%), followed by stimulants (23%), serotonin-reuptake inhibitors (SRIs) (19%), atypical antipsychotics (18%), anxiolytics (14%), anticonvulsants (11%), and typical antipsychotics (8%). Comorbid disorders and chronicity of problems were significantly associated with the receipt of certain classes of medications. Relatively few patients (18%) received psychotherapy. CONCLUSIONS: If the decision is made to treat tic disorders, the choice of medication is dependent on the primary complaints, severity, chronicity, and the presence of comorbid psychiatric disorders. In general, comorbid externalizing, anxiety and mood disorders appear to influence treatment decisions in addition to TDs.

Correlates of Length of Stay and Boarding in Florida Emergency Departments for Patients With Psychiatric Diagnoses.

OBJECTIVE: Length of stay (LOS) and boarding in the emergency department (ED) for psychiatric patients have been the subject of concern, given the problems with crowding and excessive wait times in EDs. This investigation examined correlates of LOS and boarding in Florida EDs for patients presenting with psychiatric complaints from 2010 to 2013. METHODS: Utilizing the Florida ED discharge database, the authors examined the association of LOS and boarding with hospital and encounter factors for adult patients presenting with a primary psychiatric diagnosis (N=597,541). RESULTS: The mean LOS was 7.77 hours. Anxiety disorders were the most frequent psychiatric complaint and were associated with the lowest mean LOS compared with other diagnoses (p<.05). Patient encounters resulting in a presentation of intentional self-harm and suicidality or schizophrenia were associated with significantly longer stays compared with other psychiatric diagnoses. Commercial insurance was associated with the shortest average LOS. African Americans, Hispanics, and patients age 45 and older were associated with a longer average LOS. Smaller hospital size, for-profit ownership, and rural designation were associated with a shorter average LOS. Teaching status was not associated with LOS. Furthermore, 73% of encounters resulting in transfers qualified as episodes of boarding (a stay of more than six or more hours in the ED). CONCLUSIONS: Extended LOS was endemic for psychiatric patients in Florida EDs.

Diagnoses, prevalence, and state-based federal spending for HIV prevention and treatment in the United States, 2006-2009.

BACKGROUND: In response to an article published in 2012 by officials at the US Department of Health and Human Services (DHHS), an independent analysis of state-based federal resource allocation for HIV was conducted to determine if the funding accurately reflected diagnosis and prevalence rates. METHODS: Total state-based federal funding for HIV, state-based funding for HIV prevention, and state-based funding for HIV treatment were compared to state-based HIV diagnosis and prevalence rates from 2006-2009. RESULTS: Total state-based federal funding for HIV and funding for HIV prevention and treatment were highly correlated with HIV diagnosis and prevalence rates during the time horizon of the study; however, correlations between state-based HIV prevention funding and state-based HIV diagnosis rates were lower than the correlations between state-based HIV treatment funding and HIV prevalence. CONCLUSIONS: Our findings suggest that state-based federal resource allocation for HIV prevention and treatment may be better aligned with HIV diagnosis and prevalence rates than previously reported; however resource allocation for HIV prevention is less aligned than funding for HIV treatment signaling the need to reexamine state-based federal funding for HIV prevention.

Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.

Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.

Injuries due to falls from hunters' tree stands in Pennsylvania.

BACKGROUND: People who hunt deer from elevated tree stands may improve the chances of a successful hunt but also risk serious injury from a fall to the ground. PURPOSE: The objective of the current investigation is to estimate the rates of injuries from falls from tree stands using a population-based study design. METHODS: Annual and age-specific rates were calculated using injury data collected from 1987 to 2006 from all accredited Pennsylvania trauma centers and hunting license sales and game-take mail surveys from the Pennsylvania Game Commission. RESULTS: From 1987 through 2006, 2.73 people (n=499) per 100,000 licensed deer hunters were injured from falls from tree stands; seven people died. Rates increased from 0.59 in 1987 to 7.08 in 2006 (p<0.001). Rates increased with age (p<0.001) and were highest among hunters aged 40-49 years. The case-fatality rate was 1.4%. CONCLUSIONS: Falls from tree stands associated with deer hunting are an increasing and important cause of injuries, especially for older hunters. Surveillance for tree stand-related injuries should be enhanced and preventive initiatives developed and tested.

Surgeon radiation exposure in ESS with balloon catheters.

OBJECTIVE: Less invasive instruments such as balloon catheters are available for sino-ostial dilation during endoscopic sinus surgery (ESS). Currently, balloon catheter position is confirmed under fluoroscopic visualization. Radiation exposure has been an area of concern. This study was initiated to determine surgeon radiation exposure when fluoroscopy is used during ESS with balloon catheters. STUDY DESIGN: A multi-center, prospective evaluation of surgeon radiation exposure was conducted. SUBJECTS AND METHODS: For three months, 14 sinus surgeons wore dosimeters to record radiation exposure while using C-arm fluoroscopy during balloon catheter-aided sinus surgery. One dosimeter was placed at collar level (chest), outside the lead apron and another dosimeter was placed on a finger (extremity). These dosimeters were sent for readings. Deep, eye, and shallow radiation dose for each surgeon was calculated. RESULTS: Thirteen chest badges recorded annualized averages of 191.08, 193.54, and 187.69 mrems for deep, eye, and shallow exposure respectively. Eleven ring badges recorded 584.00 mrems. CONCLUSIONS: A recent publication reported low levels of surgeon radiation exposure during ESS with balloon catheters. This study validates radiation exposure among experienced surgeons is well below the annual occupational radiation exposure limit of 50,000 mrem. With vigilant technique and education, fluoroscopy reliance can be minimized.

Effects of anesthesia on DPOAE level and phase in rats.

Many studies of the auditory system are performed on animals under general anesthesia. A concern for researchers is that these agents may significantly alter the underlying neurophysiologic mechanisms being studied. The effects may very across species, and even among individuals within a species. An investigation was undertaken to study whether DPOAE measures differ using three different anesthetic regimens: acetylpromazine-ketamine, xylazine-ketamine, and sodium pentobarbital. The same rat was anesthetized in three consecutive weeks using a different anesthetic regimen each week. DPOAE magnitude and phase temporal responses were recorded from which several measures were taken: DPOAE levels at the onset of the primaries, changes in DPOAE level as a function of time during presentation of the primaries (DeltaLI) and changes in DPOAE level (DeltaLC) and phase (DeltaPC) during presentation of a broad-band noise presented contralateral to the probe. Each week the same measurements were repeated with the rat anesthetized using a different regimen and at the end of the third week, the middle ear muscles were sectioned and the measurements repeated once again. Results showed that the anesthetic regimens did not differentially alter the DPOAE onset levels. When sodium pentobarbital was used as the anesthetic regimen, DeltaLC and DeltaPC were significantly smaller relative to those measured when the rats were anesthetized with acetylpromazine-ketamine and xylazine-ketamine. Based on the assumption that large, positive (DeltaPC) values are related to middle ear muscle activation, the middle ear muscle reflex remained at least partially active in some rats under sodium pentobarbital anesthesia. The DeltaLI measures were significantly smaller when the animals were anesthetized with xylazine-ketamine and sodium pentobarbital than when they were anesthetized with acetylpromazine-ketamine. Recordings taken after sectioning the middle ear muscles suggested that the middle ear muscle reflex substantially contributes to DeltaLC and DeltaPC measures under the anesthetic regimens xylazine-ketamine and acetylpromazine-ketamine. Data indicated that anesthetic agents variably alter neurophysiologic mechanisms involved with the complex control of the auditory signal even among individuals in the same species. Extreme care should be taken when comparing DeltaLI, DeltaLC and DeltaPC across studies when different anesthetic regimens are used within and across species.