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Ear- and hearing-related conditions pose a significant global health burden, yet public health policy surrounding ear and hearing care (EHC) in low- and middle-income countries is poorly understood. The present study aims to characterize the inclusion of EHC in national health policy by analysing national health policies, strategies and plans in English, French, Spanish, Portuguese and Arabic. Three EHC keywords were searched, including ear*, hear* and deaf*. The terms ‘human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)’, ‘tuberculosis’ and ‘malaria’ were included as comparison keywords as these conditions have historically garnered political priority in global health. Of the 194 World Health Organization Member States, there were 100 national policies that met the inclusion criteria of document availability, searchable format, language and absence of an associated national EHC strategy. These documents mentioned EHC keywords significantly less than comparison terms, with mention of hearing in 15 documents, ears in 11 documents and deafness in 3 documents. There was a mention of HIV/AIDS in 92 documents, tuberculosis in 88 documents and malaria in 70 documents. Documents in low- and middle-income countries included significantly fewer mentions of EHC terms than those of high-income countries. We conclude that ear and hearing conditions pose a significant burden of disease but are severely underrepresented in national health policy, especially in low- and middle-income countries.

Background: Elevated systolic blood pressure (SBP) has been linked to pre-procedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the relationship between blood pressure parameters including mean arterial pressure (MAP) with rebleeding both prior to and during aneurysm securement remains unclear. This study seeks to determine the association between BP parameters and rebleeding events and outcomes in patients with aSAH. Design/Methods: We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center between July 2016 and March 2021. All BP parameters, which were recorded on an hourly basis from admission, were reviewed. Per our institutional protocol, the SBP target is Results: The cohort included 295 patients (mean age 57 years [SD 13.4], 61% female, 87% received endovascular treatments, 13% surgical clipping). Two or more consecutive SBP values >140 were seen in 41% and >160 in 15% of patients. Rebleeding prior or during securing aneurysms including intra-procedural bleeding occurred in 53 patients (18%). There was no association between either maximum recorded SBP (169.7 mmHg [36.2] vs. 166.9 [32.7], p=0.57) or MAP (121 mmHg [22.9] vs. 117.8 [22.9], p=0.42) and rebleeding. However, maximum recorded MAP was associated with poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.006-1.02, p=0.039). Conclusions: Elevated MAP peri-securement of a ruptured cerebral aneurysm can be associated with poor outcome. Multicenter prospective studies should further examine the association between MAP cut offs and outcomes to be considered in guidelines.

To accurately examine the trends in the racial and gender composition of medical students applying and matriculating to urology residency programs.Reports on race/ethnicity and gender for medical school graduates, and urology residency applicants and matriculants were obtained for years 2010-2018. The proportions of individuals representing different racial and gender identities among urology applicants and matriculants were divided by a denominator of their proportion in medical school graduating classes to produce representation quotients (RQAsian men experienced increases in representation among urology applicants (RQWomen and Black men are underrepresented in the urology workforce. These concerning findings demonstrate the dire need for initiatives regarding recruitment into urology to support and to ensure successful entry into the field for minority groups.

Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients.We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD).The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome.Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Background Trauma is the leading cause of death for young Americans. Nonspecific histone deacetylase inhibitors, such as valproic acid, have been shown to improve survival in preclinical models of lethal trauma, hemorrhage, and sepsis. The doses needed to achieve a survival benefit are higher than Food and Drug Administration-approved doses, and the nonspecificity raises concerns about unintended adverse effects. The isoform-specific histone deacetylase 6 inhibitor, ACY-1083, has been found to be as efficacious as valproic acid in a rodent model of hemorrhagic shock. We hypothesized that ACY-1083 treatment would improve survival in a swine model of lethal hemorrhage, polytrauma, and bacteremia. Methods Swine were subjected to 45% blood volume hemorrhage, brain injury, femur fracture, rectus crush, splenic and liver lacerations, and colon injury. After 1 hour of shock (mean arterial pressure, 30-35 mm Hg), animals were randomized to normal saline resuscitation (control) or normal saline plus ACY-1083 30 mg/kg treatment (n = 5/group). After 3 hours (simulating delayed evacuation), packed red blood cells and antibiotics were administered, the colon injury was repaired, and the abdomen was closed. Animals were then monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. Results This combination of injuries was lethal. All animals became bacteremic, in addition to the severe hemorrhagic shock. Survival in the control group was 0%, and ACY-1083 treatment increased survival to 80% (p = 0.019). There was no difference in the brain lesion size between the groups. Conclusion A single dose of ACY-1083 markedly improves survival in an otherwise lethal model of polytrauma, hemorrhagic shock, and bacteremia.

Introduction: Aneurysmal Subarachnoid Hemorrhage (aSAH) is often accompanied by an extended length of stay (LOS) in the intensive care unit (ICU), at tremendous cost to both the hospital system and the patient. We sought to determine predictors for ICU LOS in these patients. Methods: We performed a retrospective study of a cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed in survivors to identify predictors for ICU LOS among factors present on admission and those related to hospital course. Results: In a cohort of 306 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. ICU LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p Conclusion: Admission-related factors and in-hospital complications were more predictive for prolonged ICU LOS than past medical history or any laboratory values on admission. Early neurological improvement was associated with shorter ICU LOS which underscores the importance of early aggressive treatment measures in patients with aSAH.

Cerebral vasospasm (cVSP) is a common complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP remains poorly understood. We sought to determine the association between asymptomatic cVSP and hospital length of stay (LOS), duration of external ventricular drain (EVD), and functional outcome. We performed a retrospective cohort study of consecutive aSAH patients who were admitted to an academic referral center from 2016 to 2021. We included patients with confirmed aneurysmal etiology who received transcranial Doppler (TCD) with documented daily measurements. Multiple linear regression analysis was performed to test the association of asymptomatic cVSP (defined as elevated TCD velocities with no clinical correlation) and both hospital LOS and duration of EVD. Binary logistic regression analysis was used to test the association of asymptomatic cVSP and worse functional outcome (3-month modified Rankin scale 4-6). We included 223 patients (mean age 55.8 years [SD 13.4], 60% female, 70% white) with aSAH who survived hospitalization and had documented daily TCDs. Asymptomatic cVSP was seen in 32% of patients and delayed cerebral ischemia (DCI) was seen in 27% of patients. Only symptomatic cVSP was associated with prolonged hospital LOS (3.25 more days; p=0.034) independent of age, comorbidities, Hunt and Hess grades, modified Fisher scales, DCI, and other hospital complications. However, asymptomatic cVSP was associated with longer duration of EVD (3.78 more days; p=0.025) independent of common predictors including hydrocephalus and amount of cerebrospinal fluid daily output. Severity of vasospasm (ordinal variable: mild, moderate, or severe) was associated with longer duration of EVD (1.47 more days; p=0.016). Asymptomatic cVSP was not independently associated with worse functional outcome. In conclusion, isolated asymptomatic cVSP may not be associated with worse outcome but can contribute to interventions such as EVD prolongation. Clinical significance of asymptomatic cVSP and its management should be studied in multi-institutional prospective cohorts.

BACKGROUND: No agents that are specifically neuroprotective are currently approved to emergently treat patients with traumatic brain injury (TBI). The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it not been tested in an isolated TBI model. We hypothesized that VPA, administered after isolated TBI, will penetrate the injured brain, attenuate the lesion size, and activate pro-survival pathways. METHODS: Yorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously over 1 hour; n=4) or control (saline vehicle; n=4) groups. Seven hours after injury, animals were sacrificed, and brain lesion size was measured. Mass spectrometry (MS) imaging was used to visualize and quantitate brain tissue distribution of VPA. Sequential serum samples were assayed for key biomarkers, and subjected to proteomic and pathway analysis. RESULTS: Brain lesion size was 50% smaller (p=0.01) in the VPA treated animals (3837±948 mm(3)) compared to the controls (1900±614 mm(3)). Endothelial regions had 8-fold higher VPA concentrations than perivascular regions by MS-imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared to the control animals (p

Cerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS).We performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS).The cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14).Asymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS. Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.

BackgroundTrauma and sepsis are individually two of the leading causes of death worldwide. When combined, the mortality is greater than 50%. Thus, it is imperative to have a reproducible and reliable animal model to study the effects of polytrauma and sepsis and test novel treatment options. Porcine models are more translatable to humans than rodent models due to the similarities in anatomy and physiological response. We embarked on a study to develop a reproducible model of lethal polytrauma and intra-abdominal sepsis, which was lethal, though potentially salvageable with treatment.MethodsOur laboratory has a well-established porcine model that was used as the foundation. Animals were subjected to a rectus crush injury, long bone fracture, liver and spleen laceration, traumatic brain injury and hemorrhage that was used as a foundation. We tested various colon injuries to create intra-abdominal sepsis. All animals underwent injuries followed by a period of shock, then subsequent resuscitation.ResultsAll animals had blood culture-proven sepsis. Attempts at long-term survival of animals after injury were ceased because of poor appetite and energy. We shifted to an 8-hour endpoint. The polytrauma injury pattern remained constant and the colon injury pattern changed with the intention of creating a model that was ultimately lethal but potentially salvageable with a therapeutic drug. An uncontrolled cecal injury (n=4) group resulted in very early deaths. A controlled cecal injury (CCI; n=4) group had prolonged time prior to mortality with one surviving to the endpoint. The sigmoid injury (n=5) produced a similar survival curve to CCI but no animals surviving to the endpoint.ConclusionWe have described a porcine model of polytrauma and sepsis that is reproducible and may be used to investigate novel treatments for trauma and sepsis.Level of evidenceNot applicable. Animal study.

Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury.We analyzed data from two separate experiments where swine were subjected to lethal insults. Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy.VPA treatment significantly (P0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment.A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

BACKGROUND Hemorrhage is the leading cause of preventable death in trauma. Future military conflicts are likely to be in austere environments, where prolonged damage-control resuscitation (p-DCR) may be required for 72 hours before evacuation. There is a need to demonstrate that p-DCR is feasible and to optimize its logistics. Dried plasma (DP) is a practical alternative to conventional blood products in austere settings, and valproic acid (VPA) improves survival in preclinical models of trauma and hemorrhage. We performed the current experiment to study the synergistic effects of VPA and DP and hypothesized that VPA treatment would decrease the fluid resuscitation requirements in p-DCR. METHODS Female swine were subjected to 50% hemorrhage (associated with 20% survival using non-plasma-based p-DCR) and left unresuscitated for 1 hour to simulate medic response time. They were then randomized to receive VPA (150 mg/kg + DP 250 mL; DP-VPA group; n = 5) or DP alone (DP group; n = 6). All animals were resuscitated to a systolic blood pressure of 80 mm Hg with lactated Ringer according to the Tactical Combat Casualty Care Guidelines for 72 hours, after which packed red blood cells were transfused to simulate evacuation to higher levels of care. RESULTS The DP-VPA group needed significantly (p = 0.002) less volume of lactated Ringer to reach and maintain the target systolic blood pressure. This would translate to a 4.3 L volume sparing effect for a 70-kg person. CONCLUSION Addition of a single dose of VPA significantly decreases the volume of resuscitation required in a p-DCR model.